Publications

@article{pmid37405681,

title = {Are associations between obesity and prostate cancer outcomes following radical prostatectomy the same in smokers and non-smokers? Results from the SEARCH Cohort.},

author = {Liu IT and Gu L and De Hoedt AM and Cooperberg MR and Amling CL and Kane CJ and Klaassen Z and Terris MK and Guerrios-Rivera L and Vidal AC and Aronson WJ and Freedland SJ and Csizmadi I},

url = {https://pubmed.ncbi.nlm.nih.gov/37405681/},

doi = {10.1007/s10552-023-01747-2},

issn = {0957-5243},

year  = {2023},

date = {2023-11-01},

urldate = {2023-11-01},

journal = {Cancer Causes Control},

volume = {34},

number = {11},

pages = {983-993},

abstract = {PURPOSE: Obesity and smoking have been associated with poor prostate cancer (PC) outcomes. We investigated associations between obesity and biochemical recurrence (BCR), metastasis, castrate resistant-PC (CRPC), PC-specific mortality (PCSM), and all-cause mortality (ACM) and examined if smoking modified these associations. 

METHODS: We analyzed SEARCH Cohort data from men undergoing RP between 1990 and 2020. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between body mass index (BMI) as a continuous variable and weight status classifications (normal: 18.5 ≤ 25 kg/m RESULTS: Among 6,241 men, 1,326 (21%) were normal weight, 2,756 (44%) overweight and 2159 (35%) obese; 1,841 (30%) were never-smokers, 2,768 (44%) former and 1,632 (26%) current-smokers. Among all men, obesity was associated with non-significant increased risk of PCSM, adj-HR = 1.71; 0.98-2.98, P = 0.057, while overweight and obesity were inversely associated with ACM, adj-HR = 0.75; 0.66-0.84, P < 0.001 and adj-HR = 0.86; 0.75-0.99, P = 0.033, respectively. Other associations were null. BCR and ACM were stratified for smoking status given evidence for interactions (P = 0.048 and P = 0.054, respectively). Among current-smokers, overweight was associated with an increase in BCR (adj-HR = 1.30; 1.07-1.60, P = 0.011) and a decrease in ACM (adj-HR = 0.70; 0.58-0.84, P < 0.001). Among never-smokers, BMI (continuous) was associated with an increase in ACM (adj-HR = 1.03; 1.00-1.06, P = 0.033). 

CONCLUSIONS: While our results are consistent with obesity as a risk factor for PCSM, we present evidence of effect modification by smoking for BCR and ACM highlighting the importance of stratifying by smoking status to better understand associations with body weight.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37294698,

title = {Diabetes and Prostate Cancer Outcomes in Men with Nonmetastatic Castration-Resistant Prostate Cancer: Results from the SEARCH Cohort.},

author = {Sergeyev A and Gu L and De Hoedt AM and Amling CL and Aronson WJ and Cooperberg MR and Kane CJ and Klaassen Z and Terris MK and Guerrios-Rivera L and Freedland SJ and Csizmadi I},

url = {https://pubmed.ncbi.nlm.nih.gov/37294698/},

doi = {10.1158/1055-9965.EPI-22-1324},

issn = {1055-9965},

year  = {2023},

date = {2023-09-01},

urldate = {2023-09-01},

journal = {Cancer Epidemiol Biomarkers Prev},

volume = {32},

number = {9},

pages = {1208-1216},

abstract = {BACKGROUND: The prognosis of diabetic men with advanced prostate cancer is poorly understood and understudied. Hence, we studied associations between diabetes and progression to metastases, prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) in men with nonmetastatic castration-resistant prostate cancer (nmCRPC). 

METHODS: Data from men diagnosed with nmCRPC between 2000 and 2017 at 8 Veterans Affairs Health Care Centers were analyzed using Cox regression to determine HRs and 95% confidence intervals (CI) for associations between diabetes and outcomes. Men with diabetes were classified according to: (i) ICD-9/10 codes only, (ii) two HbA1c values > 6.4% (missing ICD-9/10 codes), and (iii) all diabetic men [(i) and (ii) combined]. 

RESULTS: Of 976 men (median age: 76 years), 304 (31%) had diabetes at nmCRPC diagnosis, of whom 51% had ICD-9/10 codes. During a median follow-up of 6.5 years, 613 men were diagnosed with metastases, and 482 PCSM and 741 ACM events occurred. In multivariable-adjusted models, ICD-9/10 code-identified diabetes was inversely associated with PCSM (HR, 0.67; 95% CI, 0.48-0.92) while diabetes identified by high HbA1c values (no ICD-9/10 codes) was associated with an increase in ACM (HR, 1.41; 95% CI, 1.16-1.72). Duration of diabetes, prior to CRPC diagnosis was inversely associated with PCSM among men identified by ICD-9/10 codes and/or HbA1c values (HR, 0.93; 95% CI, 0.88-0.98). 

CONCLUSIONS: In men with late-stage prostate cancer, ICD-9/10 'code-identified' diabetes is associated with better overall survival than 'undiagnosed' diabetes identified by high HbA1c values only. 

IMPACT: Our data suggest that better diabetes detection and management may improve survival in late-stage prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37096737,

title = {Time from biopsy to radical prostatectomy by race in an equal-access healthcare system: Results from the SEARCH cohort.},

author = {Pereira V and Oyekunle T and Janes J and Amling CJ and Aronson WJ and Cooperberg MR and Kane CJ and Terris MK and Klaassen Z and Freedland SJ and Vidal AC and Csizmadi I},

url = {https://pubmed.ncbi.nlm.nih.gov/37096737/},

doi = {10.1002/pros.24542},

issn = {0270-4137},

year  = {2023},

date = {2023-08-01},

urldate = {2023-08-01},

journal = {Prostate},

volume = {83},

number = {11},

pages = {1011-1019},

abstract = {BACKGROUND: We previously showed that within an equal-access health system, race was not associated with the time between prostate cancer (PC) diagnosis and radical prostatectomy (RP). However, in the more recent time-period of the study (2003-2007), Black men had significantly longer times to RP. We sought to revisit the question in a larger study population with more contemporary patients. We hypothesized that time from diagnosis to treatment would not differ by race, even after accounting for active surveillance (AS) and the exclusion of men at very low to low risk of PC progression. 

METHODS: We analyzed data from 5885 men undergoing RP from 1988 to 2017 at eight Veterans Affairs Hospitals from SEARCH. Multiple linear regression was used to compare time from biopsy to RP and to examine the risk of delays (>90 and >180 days) between races. In sensitivity analyses we excluded men deemed to have initially chosen AS based on having >365 days from biopsy to RP and men at very low to low PC risk for progression according to National Comprehensive Cancer Network Clinical Practice Guidelines. RESULTS: At biopsy, Black men (n = 1959) were younger, had lower body mass index, and higher prostate specific antigen levels, (all p < 0.02), compared to White men (n = 3926). Time from biopsy to RP was longer in Black men (mean days: 98 vs. 92; adjusted ratio of mean number of days, 1.07 [95% confidence interval: 1.03-1.11], p < 0.001); however, there were no differences in delays >90 or >180 days after adjusting for confounders (all p ≥ 0.286). Results were similar following the exclusion of men potentially under on AS and at very low and low risk. 

CONCLUSIONS: In an equal-access healthcare system, we did not find evidence of clinically relevant differences in time from biopsy to RP in Black versus White men.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37031461,

title = {A modeling study to estimate prostate cancer-specific mortality on active surveillance for men with favorable intermediate-risk prostate cancer: Results from the SEARCH cohort.},

author = {Kuhlmann PK and Oyekunle T and Klaassen Z and Amling CL and Aronson WJ and Cooperberg MR and Kane CJ and Terris MK and Freedland SJ},

url = {https://pubmed.ncbi.nlm.nih.gov/37031461/},

doi = {10.1002/cam4.5805},

issn = {2045-7634},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Cancer Med},

volume = {12},

number = {9},

pages = {10931-10938},

abstract = {PURPOSE: Limited data exist to help surgeons decide between active surveillance (AS) versus treatment for men with favorable intermediate risk (FIR) prostate cancer. To estimate the theoretical excess risk of prostate cancer-specific mortality (PCSM) with AS versus radical prostatectomy (RP), we determined the risk of PCSM in FIR men undergoing RP and modeled the PCSM risk for AS using a range of increased PSCM scenarios ranging from 1.25x to 2x higher relative to RP. 

MATERIALS AND METHODS: We retrospectively reviewed data from men undergoing RP from 1988 to 2017 at 8 Veterans Affairs hospitals within the SEARCH cohort. Men with FIR PC were identified using the NCCN risk criteria. Risk of PCSM at 5, 10, and 15 years after RP was estimated. Using these estimates, PCSM was then modeled for AS using a range of increased risk of PCSM relative to RP ranging from 1.25x to 2x higher. 

RESULTS: For the 920 FIR men identified, 5-, 10-, and 15-year survival estimates for PCSM after RP were 99.9%, 99.0%, and 97.8%, respectively. If the risk of PCSM on AS were 1.25-2x greater than RP, there would be 0.54%-2.17% excess risk of PCSM at 15 years. 

CONCLUSIONS: The risk of death for FIR after RP is very low. Assuming even modestly increased PCSM with AS versus RP, the excess risk of death for AS in FIR is low even up to 15 years. These data support the consideration of AS as a relatively safe alternative to RP in FIR men, though prospective randomized trials are needed to validate these findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36050455,

title = {Is time to castration resistant prostate cancer a potential intermediate end-point for time to metastasis among men initiating androgen deprivation therapy for non-metastatic prostate cancer with rapid PSA doubling time (<9 months)?},

author = {Klaassen Z and Howard L and Wallis CJD and Janes JL and De Hoedt A and Aronson WJ and Polascik TJ and Amling CJ and Kane CJ and Cooperberg MR and Terris MK and Wu Y and Freedland SJ},

url = {https://pubmed.ncbi.nlm.nih.gov/36050455/},

doi = {10.1038/s41391-022-00585-8},

issn = {1365-7852},

year  = {2022},

date = {2022-09-01},

urldate = {2022-09-01},

journal = {Prostate Cancer Prostatic Dis},

abstract = {PURPOSE: Metastasis-free survival (MFS) is a surrogate for overall survival (OS) in men with non-metastatic castration-resistant prostate cancer (CRPC), but this endpoint may take years to develop in men with non-metastatic castrate-sensitive disease. The study objective was to examine whether progression to CRPC is a potential intermediate endpoint for developing metastatic disease in patients with biochemical recurrence (BCR) after radical prostatectomy (RP). 

 MATERIALS AND METHODS: Men with BCR following RP who had PSA doubling times (PSADT) < 9 months and no metastasis at the time of initiating androgen deprivation therapy (ADT) (n = 210) were included. The primary objective was to assess the correlation between CRPC-free survival (CRPC-FS) and MFS, and the secondary objective was to assess the correlation between time to metastasis and time to CRPC. Kendall's Tau was used to test the correlation for the primary and secondary outcomes. 

 

RESULTS: The median MFS was 104 months (95% CI: 83-114) and median CRPC-FS was 100 months (95% CI: 80-114). Based on the Kaplan-Meier curve, the greatest difference in time to MFS and CRPC-FS was around 70% free survival, which was reached at 61.2 months for MFS and 49.6 months for CRPC-FS. Kendall's Tau for the correlation between CRPC-FS and MFS and between time to CRPC and time to metastasis was 0.867 (95% CI: 0.765-0.968) and 0.764 (95% CI: 0.644-0.884), respectively. 

 

CONCLUSIONS: Given the high correlation between CRPC-FS and MFS, after validation, CRPC-FS may serve as a potential intermediate endpoint in trials for men with BCR initiating ADT following local therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35668181,

title = {Validation of the prostate cancer comorbidity index in predicting cause-specific mortality in men undergoing radical prostatectomy.},

author = {Chen MS and Howard LE and Stock S and Dolgner A and Freedland SJ and Aronson W and Terris M and Klaassen Z and Kane C and Amling C and Cooperberg M and Daskivich TJ},

url = {https://pubmed.ncbi.nlm.nih.gov/35668181/},

doi = {10.1038/s41391-022-00550-5},

issn = {1365-7852},

year  = {2022},

date = {2022-06-01},

urldate = {2022-06-01},

journal = {Prostate Cancer Prostatic Dis},

abstract = {PURPOSE: Accurate prediction of competing risks of mortality remains a key component of prostate cancer treatment decision-making. We sought to validate the Prostate Cancer Comorbidity Index (PCCI) score for predicting other-cause mortality (OCM) and cancer outcomes in men undergoing radical prostatectomy (RP). 

 

MATERIALS AND METHODS: We sampled 4857 men with prostate cancer treated with RP in the VA from 2000-2018. Risks of OCM, 90-day all-cause mortality (ACM), prostate cancer-specific mortality, metastasis, and biochemical recurrence by PCCI score were assessed using Cox proportional hazards and logistic regression. We compared prediction of 90-day ACM between PCCI and the American Society of Anesthesiology (ASA) score, a validated predictor of short-term mortality. 

 

RESULTS: Over median follow-up of 6.7 years (IQR 3.7-10.3), there was a stepwise increase in risk of OCM with higher PCCI score, with hazards (95%CI) of 1.53 (1.14-2.04), 2.11 (1.55-2.88), 2.36 (1.68-3.31), 3.61 (2.61-4.98), and 4.99 (3.58-6.96) for PCCI 1-2, 3-4, 5-6, 7-9, and 10 + (vs. 0), respectively. Projected 10-year cumulative incidence of OCM was 8%, 12%, 16%, 19%, 26%, and 32% for scores of 0, 1-2, 3-4, 5-6, 7-9, and 10+ , respectively. Men with PCCI 7+ had greater odds of 90-day ACM (OR 3.48, 95%CI 1.26-9.63) while men with higher ASA did not. Higher PCCI score was associated with worse cancer outcomes, with the highest categories driving the associations. 

 

CONCLUSIONS: The PCCI is a robust measure of short- and long-term OCM after RP, validated for use in clinical care and health services research focusing on surgical patient populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35243395,

title = {Red Blood Cell Distribution Width Is Associated with All-cause Mortality but Not Adverse Cancer-specific Outcomes in Men with Clinically Localized Prostate Cancer Treated with Radical Prostatectomy: Findings Based on a Multicenter Shared Equal Access Regional Cancer Hospital Registry.},

author = {Orabi H and Howard L and Amling CL and Aronson WJ and Cooperberg MR and Kane CJ and Terris MK and Klaassen Z and Janes JL and Freedland SJ and Polascik TJ},

url = {https://pubmed.ncbi.nlm.nih.gov/35243395/},

doi = {10.1016/j.euros.2022.01.003},

issn = {2666-1691},

year  = {2022},

date = {2022-03-01},

urldate = {2022-03-01},

journal = {Eur Urol Open Sci},

volume = {37},

pages = {106-112},

abstract = {Background: Recent reports with a small number of patients showed an association of red blood cell distribution width (RDW) with prostate cancer (PCa) progression. 

 

Objective: To investigate whether preoperative RDW can serve as a prognostic marker in patients with PCa undergoing radical prostatectomy (RP) in a large, equal access, and diverse patient cohort. 

 

Design setting and participants: Data were retrospectively collected on 4756 men treated with RP at eight Veteran Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 1999 through 2017. 

 

Outcome measurements and statistical analysis: Biochemical recurrence (BCR) was the primary outcome, while metastasis, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) were secondary outcomes. 

 

Results and limitations: The mean (standard deviation) age was 62 yr (6.1), and 1589 (33%) men were black. The median (interquartile range) follow-up was 82 mo (46-127). Preoperative RDW either as a continuous variable or when stratified by quartiles was not associated with BCR. Likewise, preoperative RDW was not associated with metastases or PCSM. However, higher RDW was significantly associated with higher ACM, both as a continuous variable ( 

 

Conclusions: Preoperative RDW was not associated with PCa outcomes in men treated with RP but was associated with ACM. While RDW may be a biomarker of overall health, it is not a biomarker for PCa outcomes. These results emphasize the importance of diverse, larger sized studies in genitourinary cancer research. 

 

Patient summary: Prostate cancer includes a wide spectrum of diseases with different genetic, pathological, and oncological behaviors. Red blood cell distribution width is helpful in predicting the overall survival for a localized prostate cancer patient, and hence, it can help inform personalized treatment decisions and operative care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34905632,

title = {Prostate weight and prostate cancer outcomes after radical prostatectomy: Results from the SEARCH cohort study.},

author = {Barlow SK and Oyekunle T and Janes JL and De Hoedt AM and Aronson WJ and Kane CJ and Amling CL and Cooperberg MR and Klaassen ZW and Terris MK and Freedland SJ and Csizmadi I},

url = {https://pubmed.ncbi.nlm.nih.gov/34905632/},

doi = {10.1002/pros.24283},

issn = {0270-4137},

year  = {2021},

date = {2021-12-01},

urldate = {2021-12-01},

journal = {Prostate},

abstract = {BACKGROUND: Smaller prostates have been linked to unfavorable clinical characteristics and poor short-term outcomes following radical prostatectomy (RP). We examined the relation between prostate weight at RP and prostate cancer (PC) outcomes post-RP. 

 METHODS: Men in the SEARCH cohort undergoing RP between 1988 and 2017 (N = 6242) were studied for PC-specific mortality (PCSM) as the primary outcome, and for biochemical recurrence (BCR), castration-resistant PC (CRPC) and metastasis as secondary outcomes. Hazard ratios (HR) and 95% confidence intervals (CI) were determined for associations between prostate weight and outcomes using Fine-Gray competing risk regression multivariable analyses. Sensitivity analyses were also carried out following exclusion of: (i) men with extreme prostate weights (<20 g and ≥100 g); and (ii) men with elevated prostate specific antigen (PSA) levels. 

 RESULTS: Median values for age, pre-RP PSA and prostate weight were 63 years, 6.6 ng/ml, and 42.0 g, respectively. During a median follow-up of 7.9 years, 153 (3%) died from PC, 2103 (34%) had BCR, 203 (3%) developed CRPC, and 289 (5%) developed metastases. Prostate weight was not associated with PCSM in the main analyses (multivariable HR = 1.43; 95% CI: 0.87-2.34) or in sensitivity analyses. Prostate weight was inversely associated with BCR in the main analyses (multivariable HR = 0.70; 95%CI: 0.61-0.79) which was unchanged in sensitivity analyses. HRs for prostate weight and CRPC and metastasis were elevated but statistical significance was not attained. Similar results were observed in sensitivity analyses. 

 

CONCLUSIONS: Inconsistent results for prostate weight and short-term vs longer-term outcomes highlight the need to better understand the complex biology leading to prostate size and the relevance of prostate size as a predictor of PC outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34694910,

title = {Association between Delay to Radical Prostatectomy and Clinically Meaningful Outcomes among Patients with Intermediate and High-Risk Localized Prostate Cancer.},

author = {Lee MC and Erickson TR and Stock S and Howard LE and De Hoedt AM and Amling CL and Aronson WJ and Cooperberg MR and Kane CJ and Terris MK and Klaassen Z and Freedland SJ and Wallis CJD},

url = {https://pubmed.ncbi.nlm.nih.gov/34694910/},

doi = {10.1097/JU.0000000000002304},

issn = {0022-5347},

year  = {2021},

date = {2021-10-01},

urldate = {2021-10-01},

journal = {J Urol},

pages = {101097JU0000000000002304},

abstract = {PURPOSE: There are limited data regarding the effect of treatment delays on important long-term outcomes among men with intermediate/high-risk prostate cancer (PC). 

 

MATERIALS AND METHODS: We identified 3,962 men with intermediate/high-risk disease from the SEARCH cohort treated with radical prostatectomy (RP) from 1988 to 2018. Cox proportional hazard models assessed the association between time from biopsy to RP (up to 1 year) and time to castration-resistant PC (CRPC), metastasis and all-cause mortality. Interaction terms were used to test for effect modification by risk group. 

 RESULTS: Of the 3,962 men, 167 developed CRPC, 248 developed metastases and 884 died after a median followup of 85 months. Longer delays between biopsy and RP were associated with a decreased risk of CRPC (adjusted HR=0.88, 95% CI: 0.80-0.98, p=0.02), independent of D'Amico risk group (interaction p >0.05). In men with intermediate and high-risk disease, we found no statistically significant association between length of time to RP and risk of developing metastases (p=0.5 and 0.9, respectively) or all-cause mortality (p=0.1 and 0.1, respectively). 

 

CONCLUSIONS: Among men with intermediate and high-risk PC, we found no statistically significant increased risk of adverse long-term outcomes, including CRPC, metastasis and death, for men who had treatment delays up to 1 year following PC diagnosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34081138,

title = {Time Trends in Use of Radical Prostatectomy by Tumor Risk and Life Expectancy in a National Veterans Affairs Cohort},

author = {Kristina Vaculik and Michael Luu and Lauren E Howard and William Aronson and Martha Terris and Christopher Kane and Christopher Amling and Matthew Cooperberg and Stephen J Freedland and Timothy J Daskivich},

url = {https://pubmed.ncbi.nlm.nih.gov/34081138/},

doi = {10.1001/jamanetworkopen.2021.12214},

issn = {2574-3805},

year  = {2021},

date = {2021-06-01},

urldate = {2021-06-01},

journal = {JAMA Netw Open},

volume = {4},

number = {6},

pages = {e2112214},

abstract = {Importance: Guidelines endorse using tumor risk and life expectancy (LE) to select appropriate candidates for radical prostatectomy (RP), recommending against treatment of most low-risk tumors and men with limited LE.



Objective: To investigate time trends in the use of RP by tumor risk and Prostate Cancer Comorbidity Index (PCCI) score in a contemporary, nationally representative Veterans Affairs (VA) cohort.



Design, Setting, and Participants: This cohort study of 5736 men treated with RP at 8 VA hospitals from January 1, 2000, to December 31, 2017, used a nationally representative, multicenter sample from the VA SEARCH (Shared Equal Access Regional Cancer Hospital) database. Statistical analysis was performed from June 30, 2018, to August 20, 2020.



Main Outcomes and Measures: Stratified linear and log-linear Poisson regressions were used to estimate time trends in the proportion of men treated with RP across American Urological Association tumor risk and PCCI (a validated predictor of LE based on age and comorbidities) subgroups.



Results: Among 5736 men (mean [SD] age at surgery, 62 [6] years) treated with RP from 2000 to 2017, the proportion of low-risk tumors treated with RP decreased from 51% to 7% (difference, -44%; 95% CI, -50% to -38%). The proportion of intermediate-risk tumors treated with RP increased from 30% to 59% (difference, 29%; 95% CI, 23%-35%), with unfavorable intermediate-risk tumors increasing from 30% to 41% (difference, 11%; 95% CI, 4%-18%) and favorable intermediate-risk tumors decreasing from 61% to 41% (difference, -20%; 95% CI, -24% to -15%). The proportion of high-risk tumors treated with RP increased from 18% to 33% (difference, 15%; 95% CI, 9%-21%). Among men treated with RP, the proportion with the highest PCCI scores of 10 or more (ie, LE <10 years) increased from 4% to 13% (difference, 9%; 95% CI, 4%-14%). Within each tumor risk subgroup, no significant difference in the rate of tumors treated with RP over time was found across PCCI subgroups.



Conclusions and Relevance: In this study, the use of RP shifted from low-risk and favorable intermediate-risk to higher-risk prostate cancer. However, its use among men with limited LE appears unchanged across tumor risk subgroups and increased overall.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33705584,

title = {Safety of concomitant therapy with radium-223 and abiraterone or enzalutamide in a real-world population},

author = {Hanson Zhao and Lauren E Howard and Amanda M De Hoedt and Martha K Terris and Christopher L Amling and Christopher J Kane and Matthew R Cooperberg and William J Aronson and Zachary Klaassen and Thomas J Polascik and Adriana C Vidal and Stephen J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/33705584/},

doi = {10.1002/pros.24115},

issn = {1097-0045},

year  = {2021},

date = {2021-03-11},

journal = {Prostate},

volume = {81},

number = {7},

pages = {390--397},

abstract = {BACKGROUND: Real-world utilization and outcomes of combination therapy for men with metastatic castrate-resistant prostate cancer (mCRPC) are largely unknown. We evaluated the overall survival (OS) and skeletal-related events (SREs) among men who received radium-223 with or without concomitant abiraterone or enzalutamide in the Veterans Affairs (VA) Health System.



METHODS: We reviewed charts of all mCRPC patients who received radium-223 in the VA from January 2013 to September 2017. We used Cox models to test the association between concomitant therapy versus radium-223 alone on OS and SRE. Sensitivity analyses were performed for concomitant use of denosumab/bisphosphonates.



RESULTS: Three hundred and eighteen patients treated with radium-223 were identified; 116/318 (37%) received concomitant abiraterone/enzalutamide. Two hundred and seventy-seven (87%) patients died during follow-up. Patients who received concomitant therapy were younger at radium-223 initiation (median age 68 vs. 70, p = .027) and had a longer follow-up (median 29.5 vs. 17.9 months, p = .030). There was no OS benefit for those on concomitant therapy (hazard ratio [HR]: 0.87, 95% confidence interval [CI]: 0.67-1.12, p = .28). There was a trend for an increased SRE risk for patients on concomitant therapy (HR: 1.87, 95% CI: 0.96-3.61, p = .066), but this was not significant. When analyses were limited to men using bone heath agents, similar results were seen for OS (HR: 0.86, 95% CI 0.64-1.15, p = .30) and SRE (HR: 2.36, 95% CI: 0.94-5.94, p = .068).



CONCLUSIONS: Despite the common use of concomitant therapy in this real-world study, there was no difference in OS among mCRPC patients. A nonsignificant increased SRE risk was observed. Further work needs to evaluate the optimal sequence, timing, and safety of combination therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid34169227,

title = {Diabetes and Prostate Cancer Outcomes in Obese and Nonobese Men After Radical Prostatectomy},

author = {Sonia Kelkar and Taofik Oyekunle and Adva Eisenberg and Lauren Howard and William J Aronson and Christopher J Kane and Christopher L Amling and Matthew R Cooperberg and Zachary Klaassen and Martha K Terris and Stephen J Freedland and Ilona Csizmadi},

url = {https://pubmed.ncbi.nlm.nih.gov/34169227/},

doi = {10.1093/jncics/pkab023},

issn = {2515-5091},

year  = {2021},

date = {2021-03-09},

urldate = {2021-03-09},

journal = {JNCI Cancer Spectr},

volume = {5},

number = {3},

abstract = {Background: The link between diabetes and prostate cancer progression is poorly understood and complicated by obesity. We investigated associations between diabetes and prostate cancer-specific mortality (PCSM), castrate-resistant prostate cancer (CRPC), and metastases in obese and nonobese men undergoing radical prostatectomy (RP).



Methods: We included 4688 men from the Shared Equal Access Regional Cancer Hospital cohort of men undergoing RP from 1988 to 2017. Diabetes prior to RP, anthropometric, and clinical data were abstracted from 6 Veterans Affairs Medical Centers electronic medical records. Primary and secondary outcomes were PCSM and metastases and CRPC, respectively. Multivariable-adjusted hazard ratios (adj-HRs) and 95% confidence intervals (CIs) were estimated for diabetes and PCSM, CRPC, and metastases. Adjusted hazard ratios were also estimated in analyses stratified by obesity (body mass index: nonobese <30 kg/m; obese ≥30 kg/m). All statistical tests were 2-sided.



Results: Diabetes was not associated with PCSM (adj-HR = 1.38, 95% CI = 0.86 to 2.24), CRPC (adj-HR = 1.05, 95% CI = 0.67 to 1.64), or metastases (adj-HR = 1.01, 95% CI = 0.70 to 1.46), among all men. Interaction terms for diabetes and obesity were statistically significant in multivariable models for PCSM, CRPC, and metastases ( ≤ .04). In stratified analyses, in obese men, diabetes was associated with PCSM (adj-HR = 3.06, 95% CI = 1.40 to 6.69), CRPC (adj-HR = 2.14, 95% CI = 1.11 to 4.15), and metastases (adj-HR = 1.57, 95% CI = 0.88 to 2.78), though not statistically significant for metastases. In nonobese men, inverse associations were suggested for diabetes and prostate cancer outcomes without reaching statistical significance.



Conclusions: Diabetes was associated with increased risks of prostate cancer progression and mortality among obese men but not among nonobese men, highlighting the importance of aggressively curtailing the increasing prevalence of obesity in prostate cancer survivors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37145618,

title = {The Impact of Comorbidity and Age on Timing of Androgen Deprivation Therapy in Men with Biochemical Recurrence after Radical Prostatectomy.},

author = {Moradzadeh A and Howard LE and Freedland SJ and Amling CL and Aronson WJ and Cooperberg MR and Kane CJ and Klaassen Z and Terris MK and Daskivich TJ},

url = {https://pubmed.ncbi.nlm.nih.gov/37145618/},

doi = {10.1097/UPJ.0000000000000189},

issn = {2352-0779},

year  = {2021},

date = {2021-03-01},

urldate = {2021-03-01},

journal = {Urol Pract},

volume = {8},

number = {2},

pages = {238-245},

abstract = {INTRODUCTION: Older men with major comorbidities have higher risks of morbidity and mortality from androgen deprivation therapy, and the benefits of immediate androgen deprivation therapy after biochemical recurrence in these men are unclear. We assessed variation in timing of androgen deprivation therapy by age and comorbidity in a cohort of men with biochemical recurrence after radical prostatectomy. 

METHODS: We analyzed 2,097 men with biochemical recurrence after radical prostatectomy from 2000 to 2017 in the VA SEARCH database. We ascertained age and Deyo-Charlson comorbidity index scores at biochemical recurrence. Kaplan-Meier analysis and multivariable logistic regression were used to determine association of age and Deyo-Charlson comorbidity index with prostate specific antigen at the initiation of androgen deprivation therapy. RESULTS: In Kaplan-Meier analysis with prostate specific antigen at androgen deprivation therapy as the outcome, median prostate specific antigen at androgen deprivation therapy initiation was 6.2 ng/ml (95% CI 5.1-7.1) across all patients but differed among those who received adjuvant/salvage radiation (3.6 ng/ml, 95% CI 2.8-4.3) and those who did not (12.1 ng/ml, 95% CI 9.6-15.2, p <0.001). In multivariable Cox regression, advanced age (p=0.03) but not worse comorbidity (p=0.25) was associated higher prostate specific antigen at initiation of androgen deprivation therapy. Across all patients, prostate specific antigen at androgen deprivation therapy was lower among those <60 years old (3.7 ng/ml, 95% CI 2.6-5.8) compared to those 60-64 (5.0 ng/ml, 95% CI 3.9-6.6), 65-69 (6.6 ng/ml, 95% CI 4.9-8.8), 70-74 (8.8 ng/ml, 95% CI 6.1-12.3) and ≥75 years old (14.1 ng/ml, 95% CI 5.5-37.8). In contrast, prostate specific antigen at androgen deprivation therapy was similar among comorbidity subgroups (Deyo-Charlson comorbidity index 0: 6.3 ng/ml, 95% CI 5.0-7.9 vs Deyo-Charlson comorbidity index 3 or higher: 5.6 ng/ml, 95% CI 4.1-7.4). In general, these relationships were consistent among subgroups receiving adjuvant/salvage radiation. 

CONCLUSIONS: Men with comorbid disease at increased risk of morbidity and mortality with androgen deprivation therapy often receive androgen deprivation therapy at low prostate specific antigen values.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33392907b,

title = {Monocyte counts and prostate cancer outcomes in white and black men: results from the SEARCH database},

author = {Azeb Yirga and Taofik Oyekunle and Lauren E Howard and Amanda M De Hoedt and Matthew R Cooperberg and Christopher J Kane and William J Aronson and Martha K Terris and Christopher L Amling and Emanuela Taioli and Jay H Fowke and Zachary Klaanssen and Stephen J Freedland and Adriana C Vidal},

url = {https://pubmed.ncbi.nlm.nih.gov/33392907/},

doi = {10.1007/s10552-020-01373-2},

issn = {1573-7225},

year  = {2021},

date = {2021-01-04},

journal = {Cancer Causes Control},

volume = {32},

number = {2},

pages = {189--197},

abstract = {PURPOSE: Circulating inflammatory markers may predict prostate cancer (PC) outcomes. For example, a recent study showed that higher peripheral blood monocyte counts were associated with aggressive PC in Asian men undergoing radical prostatectomy (RP). Herein, we investigated whether peripheral monocyte count can predict long-term PC outcomes after RP in black and white men.



METHODS: We retrospectively reviewed data on 2345 men undergoing RP from 2000 to 2017 at eight Veterans Affairs hospitals. Data on monocyte count within 6 and 12 months prior to surgery were collected. The study outcomes were biochemical recurrence (BCR), castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific morality (PCSM). Cox-proportional hazard models were used to assess the associations between pre-operative monocyte count and the above-mentioned outcomes accounting for confounders.



RESULTS: Of 2345 RP patients, 972 (41%) were black and 1373 (59%) were white men. In multivariable analyses, we found no associations between monocyte count and BCR among all men (HR: 1.36, 95%CI 0.90-2.07) or when analyses were stratified by race (HR: 1.30, 95%CI 0.69-2.46, in black men; HR:1.33, 95%CI 0.76-02.33, in white men). Likewise, no overall or race-specific associations were found between monocyte count and CRPC, metastases, ACM, and PCSM, all p ≥ 0.15. Results were similar for monocyte count measured at 12 months prior to RP.



CONCLUSION: In black and white PC patients undergoing RP, peripheral monocyte count was not associated with long-term PC outcomes. Contrary to what was found in Asian populations, monocyte count was not associated with PC outcomes in this study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid33189734d,

title = {Do Hispanic Men Have Worse Outcomes After Radical Prostatectomy? Results From SEARCH},

author = {Lourdes Guerrios-Rivera and Lauren E Howard and Zachary Klaassen and Martha K Terris and Matthew R Cooperberg and Christopher L Amling and Christopher J Kane and William J Aronson and Stephen J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/33189734/},

doi = {10.1016/j.urology.2020.10.043},

issn = {1527-9995},

year  = {2020},

date = {2020-11-12},

journal = {Urology},

volume = {149},

pages = {181--186},

abstract = {OBJECTIVE: To examine the associations between ethnicity and outcomes after radical prostatectomy (RP) among Hispanics. While non-Hispanic Black men have worse prostate cancer (PC) outcomes, there are limited data on outcomes of Hispanic men, especially after RP.



METHODS: We identified 3789 White men who underwent RP between 1988 and 2017 in the Shared Equal Access Regional Cancer Hospital database. Men were categorized as Hispanic or non-Hispanic. Logistic regression was used to test the association between ethnicity and PC adverse features. Cox models were used to test the association between ethnicity and biochemical recurrence (BCR), metastases, and castration-resistant PC (CRPC). All models were adjusted for age, prostate-specific antigen, clinical stage, biopsy grade group, surgery year, and surgical center.



RESULTS: Of 3789 White men, 236 (6%) were Hispanic. Hispanic men had higher prostate-specific antigen, but all other characteristics were similar between ethnicities. On multivariable analysis, there was no difference between ethnicities in odds of extracapsular extension, seminal vesicle invasion, positive margins, positive lymph nodes, or high-grade disease (odds ratio 0.62-0.89, all P > .07). A total of 1168 men had BCR, 182 developed metastasis, and 132 developed CRPC. There was no significant association between Hispanic ethnicity and risk of BCR, metastases, or CRPC (hazards ratio 0.39-0.85, all P > .06).



CONCLUSION: In an equal access setting, we found no evidence Hispanic White men undergoing RP had worse outcomes than non-Hispanic White men. In fact, all hazard ratios were <1 and although they did not achieve statistical significance, suggest perhaps slightly better outcomes for Hispanic men. Larger studies are needed to confirm findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dess2020,

title = {Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate},

author = {Robert T Dess and Krithika Suresh and Michael J Zelefsky and Stephen J Freedland and Brandon A Mahal and Matthew R Cooperberg and Brian J Davis and Eric M Horwitz and Martha K Terris and Christopher L Amling and William J Aronson and Christopher J Kane and William C Jackson and Jason W D Hearn and Curtiland Deville and Theodore L DeWeese and Stephen Greco and Todd R McNutt and Daniel Y Song and Yilun Sun and Rohit Mehra and Samuel D Kaffenberger and Todd M Morgan and Paul L Nguyen and Felix Y Feng and Vidit Sharma and Phuoc T Tran and Bradley J Stish and Thomas M Pisansky and Nicholas G Zaorsky and Fabio Ynoe Moraes and Alejandro Berlin and Antonio Finelli and Nicola Kattan and Matthew J Schipper and Daniel E Spratt},

url = {https://pubmed.ncbi.nlm.nih.gov/33090219/



https://jamanetwork.com/journals/jamaoncology/article-abstract/2771836},

doi = {10.1001/jamaoncol.2020.4922},

year  = {2020},

date = {2020-10-22},

journal = {JAMA Oncol},

abstract = {Importance: In 2016, the American Joint Committee on Cancer (AJCC) established criteria to evaluate prediction models for staging. No localized prostate cancer models were endorsed by the Precision Medicine Core committee, and 8th edition staging was based on expert consensus.



Objective: To develop and validate a pretreatment clinical prognostic stage group system for nonmetastatic prostate cancer.



Design, setting, and participants: This multinational cohort study included 7 centers from the United States, Canada, and Europe, the Shared Equal Access Regional Cancer Hospital (SEARCH) Veterans Affairs Medical Centers collaborative (5 centers), and the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry (43 centers) (the STAR-CAP cohort). Patients with cT1-4N0-1M0 prostate adenocarcinoma treated from January 1, 1992, to December 31, 2013 (follow-up completed December 31, 2017). The STAR-CAP cohort was randomly divided into training and validation data sets; statisticians were blinded to the validation data until the model was locked. A Surveillance, Epidemiology, and End Results (SEER) cohort was used as a second validation set. Analysis was performed from January 1, 2018, to November 30, 2019.



Exposures: Curative intent radical prostatectomy (RP) or radiotherapy with or without androgen deprivation therapy.



Main outcomes and measures: Prostate cancer-specific mortality (PCSM). Based on a competing-risk regression model, a points-based Score staging system was developed. Model discrimination (C index), calibration, and overall performance were assessed in the validation cohorts.



Results: Of 19 684 patients included in the analysis (median age, 64.0 [interquartile range (IQR), 59.0-70.0] years), 12 421 were treated with RP and 7263 with radiotherapy. Median follow-up was 71.8 (IQR, 34.3-124.3) months; 4078 (20.7%) were followed up for at least 10 years. Age, T category, N category, Gleason grade, pretreatment serum prostate-specific antigen level, and the percentage of positive core biopsy results among biopsies performed were included as variables. In the validation set, predicted 10-year PCSM for the 9 Score groups ranged from 0.3% to 40.0%. The 10-year C index (0.796; 95% CI, 0.760-0.828) exceeded that of the AJCC 8th edition (0.757; 95% CI, 0.719-0.792), which was improved across age, race, and treatment modality and within the SEER validation cohort. The Score system performed similarly to individualized random survival forest and interaction models and outperformed National Comprehensive Cancer Network (NCCN) and Cancer of the Prostate Risk Assessment (CAPRA) risk grouping 3- and 4-tier classification systems (10-year C index for NCCN 3-tier, 0.729; for NCCN 4-tier, 0.746; for Score, 0.794) as well as CAPRA (10-year C index for CAPRA, 0.760; for Score, 0.782).



Conclusions and relevance: Using a large, diverse international cohort treated with standard curative treatment options, a proposed AJCC-compliant clinical prognostic stage group system for prostate cancer has been developed. This system may allow consistency of reporting and interpretation of results and clinical trial design.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ce4b07076c88e1357,

title = {Race as an Outcome Predictor after Radical Prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database},

author = {S J Freedland and C L Amling and F Dorey and C J Kane and Presti J C Jr and M K Terris and W J Aronson and Shared Equal Access Regional Cancer Hospital Database Study Group},

url = {https://pubmed.ncbi.nlm.nih.gov/12385931/},

doi = {S0090429502018472 [pii]},

isbn = {1527-9995},

year  = {2020},

date = {2020-10-01},

urldate = {2002-10-01},

journal = {Urology},

volume = {60},

number = {4},

pages = {670-674},

abstract = {OBJECTIVES: Whether race is an independent predictor of prostate-specific antigen (PSA) recurrence after RP is controversial. To compare racial differences in clinical and pathologic features and biochemical recurrence in men undergoing radical prostatectomy (RP), we used a newly established multicenter database of patients from four equal-access healthcare centers in California, the Shared Equal Access Regional Cancer Hospital (SEARCH) database. 



METHODS: A retrospective survey of 1547 patients treated with RP at four different equal-access medical centers in California between 1988 and 2001 was undertaken. Race was categorized as white (n = 1014), black (n = 338), or nonwhite-nonblack (n = 195). Patients were analyzed for racial differences in preoperative variables (age at surgery, clinical stage, PSA, and biopsy Gleason score) and surgical variables (pathologic stage, surgical Gleason score, incidence of seminal vesicle invasion, positive surgical margins, capsular penetration, and pelvic lymph node involvement). Patients were followed up for PSA recurrence. Multivariate analysis was used to determine whether race was an independent predictor of biochemical failure. 



RESULTS: Significant differences were found among the races in the preoperative factors of clinical stage, age, serum PSA, and biopsy Gleason score, although the absolute differences were small. No differences were found among the races in the pathologic features of the RP specimens, including Gleason score, pathologic stage, and incidence of positive surgical margins, capsular penetration, seminal vesicle invasion, or lymph node involvement. In both univariate and multivariate analyses, only serum PSA (P <0.001) and biopsy Gleason score (P <0.001) were significant independent predictors of time to biochemical recurrence. 



CONCLUSIONS: In a large multicenter cohort of patients from four equal-access medical care facilities in California, although racial differences were found in clinical stage, age, biopsy Gleason score, and serum PSA level at diagnosis, we found race was not an independent predictor of biochemical recurrence after RP. Race should not be used in models or nomograms predicting PSA failure after RP. The current study represents the largest series of black patients and the first large series of nonwhite-nonblack patients treated with RP reported to date. The Shared Equal Access Regional Cancer Hospital database is a valuable resource for studying patients treated with RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Crawford2020,

title = {Evolving understanding and categorization of prostate cancer: preventing progression to metastatic castration-resistant prostate cancer: RADAR IV},

author = {E David Crawford and Gerald Andriole and Stephen J Freedland and Marc Garnick and Leonard G Gomella and Jonathan Henderson and Celestia Tia Higano and Andrew Karim Kader and Christopher Kane and Thomas E Keane and Phillip J Koo and Daniel P Petrylak and Robert E Reiter and Susan F Slovin and Evan Y Yu},

url = {https://pubmed.ncbi.nlm.nih.gov/33049187/

https://www.canjurol.com/abstract.php?ArticleID=&version=1.0&PMID=33049187},

year  = {2020},

date = {2020-10-01},

journal = {Can J Urol},

volume = {27},

number = {5},

pages = {10352--10362},

abstract = {INTRODUCTION To interpret data and update the traditional categorization of prostate cancer in order to help treating clinicians make more informed decisions. These updates include guidance regarding how to best use next generation imaging (NGI) with the caveat that the new imaging technologies are still a work in progress.



Literature review.

Critical goals in prostate cancer management include preventing or delaying emergence of distant metastases and progression to castration-resistant disease. Pathways for progression to metastatic castration-resistant prostate cancer (mCRPC) involve transitional states: nonmetastatic castration-resistant prostate cancer (nmCRPC), metastatic hormone-sensitive prostate cancer (mHSPC), and oligometastatic disease. Determination of clinical state depends in part on available imaging modalities. Currently, fluciclovine and gallium-68 (⁶⁸Ga) prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) are the NGI approaches with the most favorable combination of availability, specificity, and sensitivity. PET imaging can be used to help guide treatment selection in most patients. NGI can help determine patients who are candidates for new treatments, most notably (next-generation androgen antagonists, eg, apalutamide, enzalutamide, darolutamide), that can delay progression to advanced disease.



It is important to achieve a consensus on new and more easily understood terminology to clearly and effectively describe prostate cancer and its progression to health care professionals and patients. It is also important that description of disease states make clear the need to initiate appropriate treatment. This may be particularly important for disease in transition to mCRPC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Nik-Ahd2020,

title = {Obese men undergoing radical prostatectomy: Is robotic or retropubic better to limit positive surgical margins? Results from SEARCH},

author = {Farnoosh Nik-Ahd and Lauren E Howard and William J Aronson and Martha K Terris and Zachary Klaassen and Matthew R Cooperberg and Christopher L Amling and Christopher J Kane and Stephen J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/32681540/



https://onlinelibrary.wiley.com/doi/10.1111/iju.14307},

doi = {10.1111/iju.14307},

year  = {2020},

date = {2020-10-01},

journal = {Int J Urol},

volume = {27},

number = {10},

pages = {851--857},

abstract = {To evaluate the association between obesity and positive surgical margins in patients undergoing retropubic radical prostatectomy versus robotic-assisted laparoscopic prostatectomy.



We retrospectively reviewed the data of 3141 men undergoing retropubic radical prostatectomy and 1625 undergoing robotic-assisted laparoscopic prostatectomy between 1988 and 2017 at eight Veterans Health Administration hospitals. The positive surgical margin location (peripheral, apical, bladder neck, overall) was determined from pathology reports. We adjusted for age, race, prostate-specific antigen, surgery year, prostate weight, pathological grade group, extracapsular extension, seminal vesicle invasion, hospital surgical volume and surgical method (in analyses not stratified by surgical method). Interactions between body mass index and surgical approach were tested.



Among all patients, higher body mass index was associated with increased odds of overall, peripheral and apical positive surgical margins (OR 1.02-1.03, P ≤ 0.02). Although not statistically significant, there was a trend between higher body mass index and increased odds of bladder neck positive surgical margins (OR 1.03, P = 0.09). Interactions between body mass index and surgical method were significant for peripheral positive surgical margins only (P = 0.024). Specifically, there was an association between body mass index and peripheral positive surgical margins among men undergoing retropubic radical prostatectomy (OR 1.04, P < 0.001), but not robotic-assisted laparoscopic prostatectomy (OR 1.00, P = 0.98). Limitations include lacking individual surgeon data and lacking central pathology review.



In this multicenter cohort, higher body mass index was associated with increased odds of positive surgical margins at all locations except the bladder neck. Furthermore, there was a significant association between obesity and peripheral positive surgical margins in men undergoing retropubic radical prostatectomy, but not robotic-assisted laparoscopic prostatectomy. Long-term clinical significance requires further study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vidal2020,

title = {Obesity, Race, and Long-Term Prostate Cancer Outcomes},

author = {Adriana C Vidal and Taofik Oyekunle and Lauren E Howard and Amanda de Hoedt and Christopher J Kane and Martha K Terris and Matthew R Cooperberg and Christopher Amling and Zachary Klaassen and Stephen J Freedland and William J Aronson},

url = {https://pubmed.ncbi.nlm.nih.gov/32497282/},

doi = {https://doi.org/10.1002/cncr.32906},

year  = {2020},

date = {2020-06-04},

journal = {Cancer},

abstract = {Background: The authors previously found that obesity was linked with prostate cancer (PC)-specific mortality (PCSM) among men who underwent radical prostatectomy (RP). Herein, in a larger RP cohort, the authors investigated whether the association between obesity and long-term PC outcomes, including PCSM, differed by race.



Methods: Data from 5929 patients who underwent RP and were in the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed. Prior to RP, body mass index (BMI) was measured and recorded in the medical records. BMI was categorized as normal weight (<25 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). The authors assessed the association between BMI and biochemical disease recurrence (BCR), castration-resistant prostate cancer (CRPC), metastasis, and PCSM, accounting for confounders.



Results: Of the 5929 patients, 1983 (33%) were black, 1321 (22%) were of normal weight, 2605 (44%) were overweight, and 2003 (34%) were obese. Compared with white men, black men were younger; had higher prostate-specific antigen levels; and were more likely to have a BMI ≥30 kg/m2 , seminal vesicle invasion, and positive surgical margins (all P ≤ .032). During a median follow-up of 7.4 years, a total of 1891 patients (32%) developed BCR, 181 patients (3%) developed CRPC, 259 patients (4%) had metastasis, and 135 patients (2%) had died of PC. On multivariable analysis, obesity was found to be associated with an increased risk of PCSM (hazard ratio, 1.78; 95% confidence interval, 1.04-3.04 [P = .035]). No interaction was found between BMI and race in predicting PCSM (P ≥ .88), BCR (P ≥ .81), CRPC (P ≥ .88), or metastasis (P ≥ .60). Neither overweight nor obesity was associated with risk of BCR, CRPC, or metastasis (all P ≥ .18).



Conclusions: Obese men undergoing RP at several Veterans Affairs hospitals were found to be at an increased risk of PCSM, regardless of race.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea397e4b07076c88e12d6,

title = {Race Does Not Predict Skeletal-Related Events and All-Cause Mortality in Men with Castration-Resistant Prostate Cancer},

author = {D N Patel and L E Howard and De A M Hoedt and C L Amling and W J Aronson and M R Cooperberg and C J Kane and Z W Klaassen and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/32374476/},

doi = {10.1002/cncr.32933},

isbn = {1097-0142},

year  = {2020},

date = {2020-05-01},

journal = {Cancer},

abstract = {BACKGROUND: The impact of race on prostate cancer skeletal-related events (SREs) remains understudied. In the current study, the authors tested the impact of race on time to SREs and overall survival in men with newly diagnosed, bone metastatic castration-resistant prostate cancer (mCRPC). 



METHODS: The authors performed a retrospective study of patients from 8 Veterans Affairs hospitals who were newly diagnosed with bone mCRPC in the year 2000 or later. SREs comprised pathologic fracture, spinal cord compression, radiotherapy to the bone, or surgery to the bone. Time from diagnosis of bone mCRPC to SREs and overall mortality was estimated using the Kaplan-Meier method. Cox models tested the association between race and SREs and overall mortality. 



RESULTS: Of 837 patients with bone mCRPC, 232 patients (28%) were black and 605 (72%) were nonblack. At the time of diagnosis of bone mCRPC, black men were found to be more likely to have more bone metastases compared with nonblack men (29% vs 19% with ≥10 bone metastases; P = .021) and to have higher prostate-specific antigen (41.7 ng/mL vs 29.2 ng/mL; P = .005) and a longer time from the diagnosis of CRPC to metastasis (17.9 months vs 14.3 months; P < .01). On multivariable analysis, there were no differences noted with regard to SRE risk (hazard ratio [HR], 0.80; 95% CI, 0.59-1.07) or overall mortality (HR, 0.87; 95% CI, 0.73-1.04) between black and nonblack people, although the HRs were <1, which suggested the possibility of better outcomes. 



CONCLUSIONS: No significant association between black race and risk of SREs and overall mortality was observed in the current study. These data have suggested that efforts to understand the basis for the excess risk of aggressive prostate cancer in black men should focus on cancer development and progression in individuals with early-stage disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea397e4b07076c88e12d7,

title = {Competing Risks of Mortality Among Men with Biochemical Recurrence after Radical Prostatectomy},

author = {T J Daskivich and L E Howard and C L Amling and W J Aronson and M R Cooperberg and C J Kane and Z Klaassen and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/32243242/},

doi = {10.1097/JU.0000000000001036 },

isbn = {1527-3792},

year  = {2020},

date = {2020-04-01},

journal = {The Journal of urology},

pages = {101097JU0000000000001036},

abstract = {BACKGROUND: Men with biochemical recurrence (BCR) after radical prostatectomy (RP) need information on competing risks of mortality to inform prognosis and guide treatment. We sought to quantify the risk of prostate cancer metastasis and mortality (PCSM) and other-cause mortality (OCM) across key clinical predictors. 



METHODS: We analyzed 1,225 men with BCR after RP from 2001-2017 in the VA SEARCH database. Multivariable competing risks regression was used to identify predictors and quantify cumulative incidence of metastasis, PCSM, and OCM. Recursive partitioning analysis (RPA) was used to identify optimum variable cutpoints for prediction of PCSM and OCM. 



RESULTS: Over a median follow up of 5.6 years after BCR(IQR 2.7,9.1), 243 (20%) men died of other causes and 68 (6%) died of prostate cancer. Multivariable competing risks regression showed that high D'Amico tumor risk and PSA doubling time (PSADT) at BCR<9 months were associated with metastasis and PCSM(p≤0.001); 10-year PCSM was 14% and 9% for those with high-risk tumors and PSADT<9 mos, respectively. Advanced age and worse comorbidity were associated with OCM(p≤0.001); 10-year OCM was higher among men ≥70 years with any Charlson comorbidity (1-3+) (40-49%) compared with those with none (20%). RPA identified optimal variable cutpoints for prediction of PCSM and OCM, with 10-year PCSM ranging from 3-59% and 10-year OCM ranging from 17-50% across risk subgroups. 



CONCLUSIONS: Among men with BCR after RP, there is significant heterogeneity in prognosis that can be explained by available clinical variables. Men in their 70s with any major comorbidity are 2-10 times more likely to die of other causes than prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea397e4b07076c88e12d8,

title = {Performance of clinicopathologic models in men with high risk localized prostate cancer: impact of a 22-gene genomic classifier},

author = {J J Tosoian and S R Birer and Jeffrey R Karnes and J Zhang and E Davicioni and E E Klein and S J Freedland and S Weinmann and B J Trock and R T Dess and S G Zhao and W C Jackson and K Yamoah and A D Pra and B A Mahal and T M Morgan and R Mehra and S Kaffenberger and S S Salami and C Kane and A Pollack and R B Den and A Berlin and E M Schaeffer and P L Nguyen and F Y Feng and D E Spratt},

url = {https://pubmed.ncbi.nlm.nih.gov/32231245/},

doi = {10.1038/s41391-020-0226-2 },

isbn = {1476-5608},

year  = {2020},

date = {2020-03-01},

journal = {Prostate cancer and prostatic diseases},

abstract = {BACKGROUND: Prostate cancer exhibits biological and clinical heterogeneity even within established clinico-pathologic risk groups. The Decipher genomic classifier (GC) is a validated method to further risk-stratify disease in patients with prostate cancer, but its performance solely within National Comprehensive Cancer Network (NCCN) high-risk disease has not been undertaken to date. 



METHODS: A multi-institutional retrospective study of 405 men with high-risk prostate cancer who underwent primary treatment with radical prostatectomy (RP) or radiation therapy (RT) with androgen-deprivation therapy (ADT) at 11 centers from 1995 to 2005 was performed. Cox proportional hazards models were used to determine the hazard ratios (HR) for the development of metastatic disease based on clinico-pathologic variables, risk groups, and GC score. The area under the receiver operating characteristic curve (AUC) was determined for regression models without and with the GC score. 



RESULTS: Over a median follow-up of 82 months, 104 patients (26%) developed metastatic disease. On univariable analysis, increasing GC score was significantly associated with metastatic disease ([HR]: 1.34 per 0.1 unit increase, 95% confidence interval [CI]: 1.19-1.50, p  0.05). On multivariable analysis, GC score (HR: 1.33 per 0.1 unit increase, 95% CI: 1.19-1.48, p < 0.001) and GC high-risk (vs low-risk, HR: 2.95, 95% CI: 1.79-4.87, p < 0.001) were significantly associated with metastasis. The addition of GC score to regression models based on NCCN risk group improved model AUC from 0.46 to 0.67, and CAPRA from 0.59 to 0.71. 



CONCLUSIONS: Among men with high-risk prostate cancer, conventional clinico-pathologic data had poor discrimination to risk stratify development of metastatic disease. GC score was a significant and independent predictor of metastasis and may help identify men best suited for treatment intensification/de-escalation.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea397e4b07076c88e12da,

title = {Racial Discrepancies in Overall Survival among Men Treated with (223)Radium},

author = {H Zhao and L E Howard and De A Hoedt and M K Terris and C L Amling and C J Kane and M R Cooperberg and W J Aronson and Z Klaassen and T J Polascik and A C Vidal and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/31479407/},

doi = {10.1097/JU.0000000000000524 },

isbn = {1527-3792},

year  = {2020},

date = {2020-02-01},

journal = {The Journal of urology},

volume = {203},

number = {2},

pages = {331-337},

abstract = {PURPOSE: Several recent studies on metastatic castration resistant prostate cancer demonstrated improved overall survival in black vs white men. (223)Radium is Food and Drug Administration approved for metastatic castration resistant prostate cancer based on a survival benefit in the ALSYMPCA (A Phase III Study of Radium-223 Dichloride in Patients with Symptomatic Hormone Refractory Prostate Cancer with Skeletal Metastases) trial, in which 94% of participants were white. We identified a real world population of patients with metastatic castration resistant prostate cancer who received (223)radium to compare differences in baseline characteristics and outcomes in black vs nonblack men. 



MATERIALS AND METHODS: We reviewed the charts of all men who received (223)radium in the entire Veterans Affairs system. We compared treatment patterns and baseline characteristics between black and nonblack men. We used Cox models to analyze predictors of time from (223)radium start to overall survival and time to skeletal related events. 



RESULTS: We identified 318 patients treated with (223)radium, including 87 (27%) who were black. Median followup after (223)radium initiation was 25.3 months (IQR 13.8-37.1). Black men were younger than nonblack men when starting (223)radium (median age 67 vs 70 years, p <0.001) and they had higher prostate specific antigen (median 159.9 vs 90.2 ng/ml



CONCLUSIONS: Black men had longer overall survival than nonblack men, although they appeared to receive radium later in the disease course. Further studies are required to verify our findings and explore biological differences between black and nonblack men with metastatic castration resistant prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea397e4b07076c88e12db,

title = {Serum Lipids prior to Starting Androgen Deprivation Therapy and Risk of Castration Resistant Prostate Cancer and Metastasis: Results from the SEARCH Database},

author = {S Dambal and L E Howard and E H Allott and W J Aronson and C J Kane and C L Amling and M R Cooperberg and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/31430247/},

doi = {10.1097/JU.0000000000000494 },

isbn = {1527-3792},

year  = {2020},

date = {2020-01-01},

journal = {The Journal of urology},

volume = {203},

number = {1},

pages = {120-127},

abstract = {PURPOSE: We tested the association of serum lipid levels prior to androgen deprivation therapy with the risk of castration resistant prostate cancer and metastasis. 



MATERIALS AND METHODS: We identified 302 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who received androgen deprivation therapy after radical prostatectomy for nonmetastatic disease, had never received statins before androgen deprivation therapy and had available serum lipid data within 2 years prior to androgen deprivation therapy. Cox proportional hazards models were used to test associations between total cholesterol (less than 200 vs 200 mg/dl or greater), low density lipoprotein (less than 130 vs 130 mg/dl or greater), high density lipoprotein (40 or greater vs less than 40 mg/dl) and triglycerides (less than 150 vs 150 mg/dl or greater) and the risk of castration resistant prostate cancer and metastasis after androgen deprivation therapy while adjusting for potential confounders. Subanalyses were restricted to men who remained statin nonusers after androgen deprivation therapy. 



RESULTS: Median followup after androgen deprivation therapy was 67 months. Castration resistant prostate cancer and metastasis developed in 42 and 44 men, respectively. Men with elevated cholesterol received androgen deprivation therapy in an earlier year and had longer followup and a higher rate of statin use after androgen deprivation therapy. On multivariable analysis total cholesterol and low density lipoprotein were unrelated to castration resistant prostate cancer. Low high density lipoprotein (less than 40 vs 40 mg/dl or greater) was suggestively linked to an increased risk of castration resistant prostate cancer (HR 1.86, 95% CI 0.99-3.48). The association was stronger in men who remained statin nonusers after androgen deprivation therapy (HR 3.64, 95% CI 1.45-9.17). Results for metastasis were similar to those for castration resistant prostate cancer. 



CONCLUSIONS: Among men with nonmetastatic prostate cancer who started androgen deprivation therapy serum cholesterol was unrelated to castration resistant prostate cancer or metastasis. Low high density lipoprotein was suggestively associated with risks of increased castration resistant prostate cancer and metastasis, particularly in statin never users. Further studies are needed to explore a potential role for lipids in prostate cancer progression after androgen deprivation therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e0,

title = {Validity of the National Death Index to ascertain the date and cause of death in men having undergone prostatectomy for prostate cancer},

author = {D Moghanaki and L E Howard and De A Hoedt and W J Aronson and C J Kane and C L Amling and M R Cooperberg and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/31036926/},

doi = {10.1038/s41391-019-0146-1 },

isbn = {1476-5608},

year  = {2019},

date = {2019-12-01},

journal = {Prostate cancer and prostatic diseases},

volume = {22},

number = {4},

pages = {633-635},

abstract = {BACKGROUND: The National Death Index (NDI) is a centralized database containing information from death certificates that are frequently referenced by health and medical investigators to ascertain vital statistics. Yet, it commonly includes misclassified causes of death. Since the NDI is frequently relied upon in studies that evaluate outcomes following radical prostatectomy (RP) for prostate cancer (PC), we evaluated its validity by referencing mortality data from the Shared Equal Access Regional Cancer Hospital (SEARCH) database which is a prospectively managed database of 5009 Veterans who underwent a RP at eight Veterans Affairs medical centers between 1982 and 2016. 



METHODS: We compared vital status, cause of death and date of death from the SEARCH database with the NDI. 



RESULTS: A total of 1312 men in SEARCH were deceased, yet the NDI reported 17% (219) of those men as still alive. Among the 1093 men who had concordant vital status in both SEARCH and NDI, the date of death was an exact match within one day, a week, or 31 days in 94%, 97%, 99%, and 100%, respectively. Of those men coded as dying from prostate cancer in the SEARCH database (n = 105), 12% were coded as having died from non-PC causes in the NDI. Meanwhile, among patients coded by the NDI as having died of PC (n = 139), 34% were coded in SEARCH as having died of non-PC causes. 



CONCLUSIONS: These findings demonstrate that the NDI provides accurate dates of death, but frequently misclassifies whether a death was due to prostate cancer. Studies that rely upon death certificates, as captured in the NDI, may be unreliable to report prostate cancer-specific mortality rates after prostatectomy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea397e4b07076c88e12dc,

title = {Predictors of skeletal-related events and mortality in men with metastatic, castration-resistant prostate cancer: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database},

author = {I L Tablazon and L E Howard and De A M Hoedt and W J Aronson and C J Kane and C L Amling and M R Cooperberg and M K Terris and S J Freedland and S B Williams},

url = {https://pubmed.ncbi.nlm.nih.gov/31390061/},

doi = {10.1002/cncr.32414 },

isbn = {1097-0142},

year  = {2019},

date = {2019-11-01},

journal = {Cancer},

volume = {125},

number = {22},

pages = {4003-4010},

abstract = {BACKGROUND: Although skeletal-related events (SREs) are linked with a reduced quality of life and worse outcomes, to the authors' knowledge the factors that predict SREs are minimally understood. The objective of the current study was to identify predictors of SREs and all-cause mortality among men with metastatic castration-resistant prostate cancer (mCRPC). 



METHODS: Data were collected on 837 men with bone mCRPC at 8 Veterans Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 2000 through 2017. Patients were followed to assess development of SREs (pathological fracture, radiotherapy to bone, spinal cord compression, or surgery to bone). Cox proportional hazards models were used to evaluate predictors of SREs and mortality.



RESULTS: Of the 837 men with bone mCRPC, 287 developed a SRE and 740 men died (median follow-up, 26 months). Bone pain was found to be the strongest predictor of SREs (hazard ratio [HR], 2.96; 95% CI, 2.25-3.89). A shorter time from CRPC to the development of metastasis (HR, 0.92; 95% CI, 0.85-0.99), shorter progression to CRPC (HR, 0.94; 95% CI, 0.91-0.98), and visceral metastasis at the time of diagnosis of bone metastasis (HR, 1.91; 95% CI, 1.18-3.09) were associated with an increased risk of SREs. Ten or more bone metastases (HR, 2.17; 95% CI, 1.72-2.74), undergoing radical prostatectomy (HR, 0.73; 95% CI, 0.61-0.89), shorter progression to CRPC (HR, 0.97; 95% CI, 0.94-0.99), older age (HR, 1.03; 95% CI, 1.02-1.04), higher prostate-specific antigen level at the time of diagnosis of metastasis (HR, 1.21; 95% CI, 1.14-1.28), bone pain (HR, 1.44; 95% CI, 1.23-1.70), and visceral metastasis (HR, 1.72; 95% CI, 1.23-2.39) were associated with an increased mortality risk. 



CONCLUSIONS: Among men with bone mCRPC, bone pain was found to be the strongest predictor of SREs and the number of bone metastases was a strong predictor of mortality. If validated, these factors potentially may be used for risk stratification and for SRE prevention strategies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12de,

title = {Salvage Radiotherapy for Recurrent Prostate Cancer: Can the Prognostic Grade Group System Inform Treatment Timing?},

author = {K J Tay and T J Polascik and L E Howard and J K Salama and A A Schulman and Z Chen and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/31257075/},

doi = {10.1016/j.clgc.2019.05.007},

isbn = {1938-0682},

year  = {2019},

date = {2019-10-01},

journal = {Clinical genitourinary cancer},

volume = {17},

number = {5},

pages = {e930-e938},

abstract = {PURPOSE: In order to better time salvage radiotherapy (SRT) for post-radical prostatectomy biochemical failure, we examined the association between pre-SRT prostate-specific antigen (PSA) and PSA control as a function of the new prognostic grade group (PGG) system. 



PATIENTS AND METHODS: Using the Shared Equal Access Regional Cancer Hospital database, we identified men after radical prostatectomy with PSA > 0.2 ng/mL and without cancer involvement of lymph nodes who underwent SRT alone. SRT failure was defined as post-SRT PSA nadir + 0.2 ng/mL or receipt of post-SRT hormone therapy. Men were stratified by pre-SRT PSA (0.2-0.49, 0.5-0.99, and ≥ 1.0 ng/mL). Multivariable Cox models were used to test the association between pre-SRT PSA and SRT failure, stratified by PGG. 



RESULTS: A total of 358 men met the inclusion criteria and comprised our study cohort. Median post-SRT follow-up was 78 months. A total of 174 men (49%) had pre-SRT PSA 0.2-0.49 ng/mL, 97 (27%) PSA 0.5-0.99 ng/mL, and 87 (24%) PSA ≥ 1.0 ng/mL. On multivariable analysis among men with PGG 1-2, pre-SRT PSA 0.2-0.49 ng/mL had similar outcomes as PSA 0.5-0.99 ng/mL; those with PSA ≥ 1.0 ng/mL had higher recurrence risks (hazard ratio = 2.78, P < .001). Among PGG 3-5, PSA 0.5-0.99 ng/mL or ≥ 1.0 ng/mL had a higher recurrence risk (hazard ratio = 2.15, P = .021; and hazard ratio = 2.49, P = .010, respectively) versus PSA 0.2-0.49 ng/mL. 



CONCLUSION: In men with higher-grade prostate cancer (PGG 3-5), SRT should be provided earlier (PSA < 0.5 ng/mL), while among men with lower-grade disease (PGG 1-2), SRT results in equal PSA control up to PSA 1.0 ng/mL.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12df,

title = {Influence of African American race on the association between preoperative biopsy grade group and adverse histopathologic features of radical prostatectomy},

author = {A Aminsharifi and A Schulman and L E Howard and K J Tay and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and S J Freedland and T J Polascik},

url = {https://pubmed.ncbi.nlm.nih.gov/31042315/},

doi = {10.1002/cncr.32168 },

isbn = {1097-0142},

year  = {2019},

date = {2019-09-01},

journal = {Cancer},

volume = {125},

number = {17},

pages = {3025-3032},

abstract = {BACKGROUND: The current study was performed to evaluate the influence of race on the association between biopsy grade group (GrGp) and the risk of detectable prostate-specific antigen (PSA) and adverse histopathological outcomes after radical prostatectomy (RP). 



METHODS: Data regarding 4073 men (1344 African American men; 33%) who were treated with RP were categorized based on the 5-tiered GrGp system. Logistic regression was used to test the association between biopsy GrGp and PSA nadir (<0.1 ng/mL) after RP as well as adverse pathological features among all patients and stratified by race.



RESULTS: Those patients with a higher biopsy GrGp were found to have lower odds of achieving a PSA nadir <0.1 ng/mL after RP on unadjusted and multivariable analysis (both P < .001). On unadjusted and multivariable analysis, higher GrGp was associated with increased odds of each of the adverse pathological features, namely, GrGp ≥3, extraprostatic extension, seminal vesicle invasion, positive surgical resection margin, and positive lymph nodes (all P < .001). Race had no significant interaction with biopsy GrGp in the prediction of PSA nadir after RP (P = .91) or any adverse pathological features (all P > .06) except positive lymph nodes. When the models were stratified by race, the associations between preoperative biopsy GrGp and having a PSA nadir <0.1 ng/mL, high-grade final pathology, or other adverse histopathologic features were similar in both races except as noted for positive lymph nodes.



CONCLUSIONS: Higher preoperative biopsy GrGp is associated with increased odds of adverse histopathological findings as well as lower odds of a PSA nadir <0.1 ng/mL after RP. These associations are largely independent of race, suggesting that GrGp is an accurate tool for risk stratification in both black and white men.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e1,

title = {Poorly controlled diabetes increases the risk of metastases and castration-resistant prostate cancer in men undergoing radical prostatectomy: Results from the SEARCH database},

author = {F Nik-Ahd and L E Howard and A T Eisenberg and W J Aronson and M K Terris and M R Cooperberg and C L Amling and C J Kane and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/31034601/},

doi = {10.1002/cncr.32141 },

isbn = {1097-0142},

year  = {2019},

date = {2019-08-01},

journal = {Cancer},

volume = {125},

number = {16},

pages = {2861-2867},

abstract = {BACKGROUND: Although diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP). 



METHODS: The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only. 



RESULTS: A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P < .001) and more likely to be black (P = .013). The median follow-up after RP was 6.8 years (interquartile range, 3.7-10.6 years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44 [P = .031]) and CRPC (HR, 1.27; 95% CI, 1.03-1.56 [P = .023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC-specific mortality (HR, 1.24; 95% CI, 0.99-1.56 [P = .067]) and all-cause mortality (HR, 1.09; 95% CI, 0.99-1.19 [P = .058]). 



CONCLUSIONS: Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow-up, future research should test whether better glycemic control improves long-term PC outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea397e4b07076c88e12dd,

title = {Association of Black Race With Prostate Cancer-Specific and Other-Cause Mortality},

author = {R T Dess and H E Hartman and B A Mahal and P D Soni and W C Jackson and M R Cooperberg and C L Amling and W J Aronson and C J Kane and M K Terris and Z S Zumsteg and S Butler and J R Osborne and T M Morgan and R Mehra and S S Salami and A U Kishan and C Wang and E M Schaeffer and Roach M 3rd and T M Pisansky and W U Shipley and S J Freedland and H M Sandler and S Halabi and F Y Feng and J J Dignam and P L Nguyen and M J Schipper and D E Spratt},

url = {https://pubmed.ncbi.nlm.nih.gov/31120534/},

doi = {10.1001/jamaoncol.2019.0826 },

isbn = {2374-2445},

year  = {2019},

date = {2019-07-01},

journal = {JAMA oncology},

volume = {5},

number = {7},

pages = {975-983},

abstract = {IMPORTANCE: Black men are more likely to die of prostate cancer than white men. In men with similar stages of disease, the contribution of biological vs nonbiological differences to this observed disparity is unclear. 



OBJECTIVE: To quantify the association of black race with long-term survival outcomes after controlling for known prognostic variables and access to care among men with prostate cancer. 



DESIGN, SETTING, AND PARTICIPANTS: This multiple-cohort study included updated individual patient-level data of men with clinical T1-4N0-1M0 prostate cancer from the following 3 cohorts: Surveillance, Epidemiology, and End Results (SEER [n = 296 273]); 5 equal-access regional medical centers within the Veterans Affairs health system (VA [n = 3972]); and 4 pooled National Cancer Institute-sponsored Radiation Therapy Oncology Group phase 3 randomized clinical trials (RCTs [n = 5854]). Data were collected in the 3 cohorts from January 1, 1992, through December 31, 2013, and analyzed from April 27, 2017, through April 13, 2019. 



EXPOSURES: In the VA and RCT cohorts, all patients received surgery and radiotherapy, respectively, with curative intent. In SEER, radical treatment, hormone therapy, or conservative management were received. 



MAIN OUTCOMES AND MEASURES: Prostate cancer-specific mortality (PCSM). Secondary measures included other-cause mortality (OCM). To adjust for demographic-, cancer-, and treatment-related baseline differences, inverse probability weighting (IPW) was performed. 



RESULTS: Among the 306 100 participants included in the analysis (mean [SD] age, 64.9 [8.9] years), black men constituted 52 840 patients (17.8%) in the SEER cohort, 1513 (38.1%) in the VA cohort, and 1129 (19.3%) in the RCT cohort. Black race was associated with an increased age-adjusted PCSM hazard (subdistribution hazard ratio [sHR], 1.30; 95% CI, 1.23-1.37; P < .001) within the SEER cohort. After IPW adjustment, black race was associated with a 0.5% (95% CI, 0.2%-0.9%) increase in PCSM at 10 years after diagnosis (sHR, 1.09; 95% CI, 1.04-1.15; P < .001), with no significant difference for high-risk men (sHR, 1.04; 95% CI, 0.97-1.12; P = .29). No significant differences in PCSM were found in the VA IPW cohort (sHR, 0.85; 95% CI, 0.56-1.30; P = .46), and black men had a significantly lower hazard in the RCT IPW cohort (sHR, 0.81; 95% CI, 0.66-0.99; P = .04). Black men had a significantly increased hazard of OCM in the SEER (sHR, 1.30; 95% CI, 1.27-1.34; P < .001) and RCT (sHR, 1.17; 95% CI, 1.06-1.29; P = .002) IPW cohorts. 



CONCLUSIONS AND RELEVANCE: In this study, after adjustment for nonbiological differences, notably access to care and standardized treatment, black race did not appear to be associated with inferior stage-for-stage PCSM. A large disparity remained in OCM for black men with nonmetastatic prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e3,

title = {Practice patterns and outcomes of equivocal bone scans for patients with castration-resistant prostate cancer: Results from SEARCH},

author = {B T Hanyok and M M Everist and L E Howard and De A M Hoedt and W J Aronson and M R Cooperberg and C J Kane and C L Amling and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/31297315/},

doi = {10.1016/j.ajur.2019.01.004 },

isbn = {2214-3882},

year  = {2019},

date = {2019-07-01},

journal = {Asian journal of urology},

volume = {6},

number = {3},

pages = {242-248},

abstract = {OBJECTIVE: To review follow-up imaging after equivocal bone scans in men with castration resistant prostate cancer (CRPC) and examine the characteristics of equivocal bone scans that are associated with positive follow-up imaging. 



METHODS: We identified 639 men from five Veterans Affairs Hospitals with a technetium-99m bone scan after CRPC diagnosis, of whom 99 (15%) had equivocal scans. Men with equivocal scans were segregated into "high-risk" and "low-risk" subcategories based upon wording in the bone scan report. All follow-up imaging (bone scans, computed tomography [CT], magnetic resonance imaging [MRI], and X-rays) in the 3 months after the equivocal scan were reviewed. Variables were compared between patients with a positive vs. negative follow-up imaging after an equivocal bone scan. 



RESULTS: Of 99 men with an equivocal bone scan, 43 (43%) received at least one follow-up imaging test, including 32/82 (39%) with low-risk scans and 11/17 (65%) with high-risk scans (p = 0.052). Of follow-up tests, 67% were negative, 14% were equivocal, and 19% were positive. Among those who underwent follow-up imaging, 3/32 (9%) low-risk men had metastases vs. 5/11 (45%) high-risk men (p = 0.015). 



CONCLUSION: While 19% of all men who received follow-up imaging had positive follow-up imaging, only 9% of those with a low-risk equivocal bone scan had metastases versus 45% of those with high-risk. These preliminary findings, if confirmed in larger studies, suggest follow-up imaging tests for low-risk equivocal scans can be delayed while high-risk equivocal scans should receive follow-up imaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e5,

title = {Obesity, risk of biochemical recurrence, and prostate-specific antigen doubling time after radical prostatectomy: results from the SEARCH database},

author = {S J Freedland and B L Branche and L E Howard and R J Hamilton and W J Aronson and M K Terris and M R Cooperberg and C L Amling and C J Kane and SEARCH Database Study Group},

url = {https://pubmed.ncbi.nlm.nih.gov/30347135/},

doi = {10.1111/bju.14594 },

isbn = {1464-410X},

year  = {2019},

date = {2019-07-01},

journal = {BJU international},

volume = {124},

number = {1},

pages = {69-75},

abstract = {OBJECTIVES: To examine the association between body mass index (BMI) and aggressive biochemical recurrence (BCR) using the Shared Equal Access Regional Cancer Hospital (SEARCH) database. 



MATERIAL AND METHODS: We identified 4123 men with complete data treated by radical prostatectomy between 1988 and 2015. We tested the association between BMI and BCR using Cox models, and among men with BCR, prostate-specific antigen doubling time (PSADT) was compared across BMI categories using linear regression. Models were adjusted for age, race, prostate-specific antigen, biopsy Gleason score, clinical stage, year and surgical centre. 



RESULTS: Overall, 922 men (22%) were of normal weight (BMI <25 kg/m(2) ), 1863 (45%) were overweight (BMI 25-29.9 kg/m(2) ), 968 (24%) were obese (BMI 30-34.9 kg/m(2) ), and 370 (9%) were moderately or severely obese (BMI ≥35 kg/m(2) ). After adjustment for multiple clinical characteristics, higher BMI was significantly associated with higher risk of BCR (P = 0.008). Among men with BCR, men in the four BMI categories had similar multivariable-adjusted PSADT values (increasing BMI categories: 20.9 vs 21.3 vs 21.0 vs 14.9 months; P = 0.48). 



CONCLUSION: While we confirmed that higher BMI was associated with BCR, we found no link between BMI and PSADT at the time of recurrence. Our data suggest obese men do not have more aggressive recurrences. Future studies are needed to test whether obesity predicts response to salvage therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e8,

title = {Impact of age, comorbidity, and PSA doubling time on long-term competing risks for mortality among men with non-metastatic castration-resistant prostate cancer},

author = {C A Whitney and L E Howard and S J Freedland and A M DeHoedt and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and T J Daskivich},

url = {https://pubmed.ncbi.nlm.nih.gov/30279582/},

doi = {10.1038/s41391-018-0095-0 },

isbn = {1476-5608},

year  = {2019},

date = {2019-05-01},

journal = {Prostate cancer and prostatic diseases},

volume = {22},

number = {2},

pages = {252-260},

abstract = {BACKGROUND: Understanding competing risks for mortality is critical in determining prognosis among men with non-metastatic castration-resistant prostate cancer (nmCRPC), a disease state that often affects older men and has substantial heterogeneity in risk of cancer mortality. We sought to determine the impact of age, comorbidity, and PSA doubling time (PSADT) on competing risks for mortality in men with nmCRPC. 



METHODS: We conducted a retrospective analysis of 1238 patients diagnosed with nmCRPC in 2000-2015 in the SEARCH database. Multivariable Cox proportional hazards and competing risks regression were used to determine the hazards of overall, prostate cancer-specific (PCSM), and other-cause mortality (OCM) across age, Charlson comorbidity index (CCI), and PSADT subgroups. 



RESULTS: Men with nmCRPC were elderly (median age 77) and had substantial comorbidity burdens (CCI > 1 n = 701, 57%). Multivariable Cox analysis showed higher CCI was associated with higher hazard of OCM, while slower PSADT was associated with lower hazard of PCSM across all age subgroups. Among those with CCI ≥ 3 (vs. CCI0), the hazard ratio of OCM was 2.7 (95% CI 1.1-6.3), 2.0 (95% CI 1.1-3.6), and 2.5 (95% CI 1.5-4.0) for those aged  80 with CCI ≥ 3, in whom OCM was the predominant cause of death. 



CONCLUSIONS: Among men with nmCRPC, age, comorbidity, and PSADT are associated with risk and cause of death and may assist clinicians in counseling patients regarding cancer prognosis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e4,

title = {Socioeconomic status, race, and long-term outcomes after radical prostatectomy in an equal access health system: Results from the SEARCH database},

author = {M M Everist and L E Howard and W J Aronson and C J Kane and C L Amling and M R Cooperberg and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/30598238/},

doi = {10.1016/j.urolonc.2018.12.004},

isbn = {1873-2496},

year  = {2019},

date = {2019-04-01},

journal = {Urologic oncology},

volume = {37},

number = {4},

pages = {289.e11-289.e17},

abstract = {INTRODUCTION: We previously found racial differences in biochemical recurrence (BCR) after radical prostatectomy (RP) persisted after adjusting for socioeconomic status (SES) while SES did not predict BCR. The impact on long-term prostate cancer (PC) outcomes is unclear. We hypothesized higher SES would associate with better long-term outcomes regardless of race. 



METHODS: Among 4,787 black and white men undergoing RP from 1988 to 2015 in the SEARCH Database, poverty (primary SES measure) was estimated by linking home ZIP-code to census data. Cox models were used to test the association between SES adjusting for demographic, clinicopathological features, and race with BCR, castration-resistant PC (CRPC), metastases, PC-specific mortality (PCSM), and all-cause mortality. Interactions between race and SES were tested. 



RESULTS: Median follow-up was 98 months (Interquartile range: 54-150 months). There were no interactions between race and SES for BCR. Black men had 10%- to 11% increased BCR risk (P < 0.06) while SES was unrelated to BCR. There were interactions between SES and race for CRPC (P = 0.002), metastasis (P = 0.014), and PCSM (P = 0.004). Lower SES was associated with decreased CRPC (P = 0.012), metastases (P = 0.004), and PCSM (P = 0.049) in black, but not white men (all P ≥ 0.22). Higher SES was associated with decreased all-cause mortality in both races. 



CONCLUSIONS: In an equal-access setting, lower SES associated with decreased CRPC, metastases, and PCSM in black but not white men. If confirmed, these findings suggest a complex relationship between race, SES, and PC with further research needed to understand why low SES in black men decreased the risk for poor PC outcomes after RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e2,

title = {First-year weight loss with androgen-deprivation therapy increases risks of prostate cancer progression and prostate cancer-specific mortality: results from SEARCH},

author = {K Griffin and I Csizmadi and L E Howard and G M Pomann and W J Aronson and C J Kane and C L Amling and M R Cooperberg and M K Terris and J Beebe-Dimmer and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/30701374/},

doi = {10.1007/s10552-019-1133-5 },

isbn = {1573-7225},

year  = {2019},

date = {2019-03-01},

journal = {Cancer causes & control : CCC},

volume = {30},

number = {3},

pages = {259-269},

abstract = {PURPOSE: We aimed to study the associations between androgen-deprivation therapy (ADT)-induced weight changes and prostate cancer (PC) progression and mortality in men who had undergone radical prostatectomy (RP). 



METHODS: Data from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort were used to study the associations between weight change approximately 1-year post-ADT initiation and metastases, castration-resistant prostate cancer (CRPC), all-cause mortality (ACM), and PC-specific mortality (PCSM) in 357 patients who had undergone RP between 1988 and 2014. We estimated hazard ratios (HR) and 95% confidence intervals (95% CI) using covariate-adjusted Cox regression models for associations between weight loss, and weight gains of 2.3 kg or more, and PC progression and mortality post-ADT. 



RESULTS: During a median (IQR) follow-up of 81 (46-119) months, 55 men were diagnosed with metastases, 61 with CRPC, 36 died of PC, and 122 died of any cause. In multivariable analysis, weight loss was associated with increases in risks of metastases (HR 3.13; 95% CI 1.40-6.97), PCSM (HR 4.73; 95% CI 1.59-14.0), and ACM (HR 2.16; 95% CI 1.25-3.74) compared with mild weight gains of ≤ 2.2. Results were slightly attenuated but remained statistically significant in analyses that accounted for competing risks of non-PC death. Estimates for the associations between weight gains of ≥ 2.3 kg and metastases (HR 1.58; 95% CI 0.73-3.42), CRPC (HR 1.33; 95% CI 0.66-2.66), and PCSM (HR 2.44; 95% CI 0.84-7.11) were elevated, but not statistically significant. 



CONCLUSIONS: Our results suggest that weight loss following ADT initiation in men who have undergone RP is a poor prognostic sign. If confirmed in future studies, testing ways to mitigate weight loss post-ADT may be warranted.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e6,

title = {Does race predict the development of metastases in men who receive androgen-deprivation therapy for a biochemical recurrence after radical prostatectomy?},

author = {A C Vidal and L E Howard and De A Hoedt and C J Kane and M K Terris and W J Aronson and M R Cooperberg and C L Amling and S Lechpammer and S C Flanders and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/30427535/},

doi = {10.1002/cncr.31808 },

isbn = {1097-0142},

year  = {2019},

date = {2019-02-01},

journal = {Cancer},

volume = {125},

number = {3},

pages = {434-441},

abstract = {BACKGROUND: In this study among men who underwent radical prostatectomy (RP), African American men (AAM) were 28% more likely to develop recurrent disease compared with Caucasian men (CM). However, among those who had nonmetastatic, castration-resistant prostate cancer (CRPC), race did not predict metastases or overall survival. Whether race predicts metastases among men who receive androgen-deprivation therapy (ADT) after a biochemical recurrence (BCR) (ie, before CRPC but after BCR) is untested. 



METHODS: The authors identified 595 AAM and CM who received ADT for a BCR that developed after RP between 1988 and 2015 in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database. Univariable and multivariable Cox models were used to test the association between race and the time from ADT to metastases. Secondary outcomes included the time to CRPC, all-cause mortality, and prostate cancer-specific mortality. 



RESULTS: During a median follow-up of 66 months after ADT, 62 of 354 CM (18%) and 38 of 241 AAM (16%) developed metastases. AAM were younger at the time they received ADT (63 vs 67 years; P .5). 



CONCLUSIONS: Among veterans who received ADT post-BCR after RP, race was not a predictor of metastases or other adverse outcomes. The current findings suggest that research efforts to understand racial differences in prostate cancer biology should focus on early stages of the disease (ie, closer to the time of diagnosis).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e7,

title = {Statins are Associated With Increased Biochemical Recurrence After Radical Prostatectomy in Diabetic Men but no Association was Seen in Men also Taking Metformin: Results From the SEARCH Database},

author = {A Aminsharifi and L E Howard and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and T J Polascik and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/30366879/},

doi = {10.1016/j.clgc.2018.09.020},

isbn = {1938-0682},

year  = {2019},

date = {2019-02-01},

journal = {Clinical genitourinary cancer},

volume = {17},

number = {1},

pages = {e140-e149},

abstract = {PURPOSE: To investigate the preoperative use of combination metformin and statin versus monotherapy on biochemical recurrence (BCR) after radical prostatectomy (RP) in diabetic men. PATIENTS AND 



METHODS: Data of 843 diabetic men who underwent RP were stratified on the basis of preoperative use of no drug or of metformin, statin, or both. Multivariable Cox models were used to test the association between treatment and BCR. In a secondary analysis, models were stratified by race and body mass index (BMI) and further adjusted for glycated hemoglobin (HbA1c). 



RESULTS: A total of 259 men (31%) received statin therapy, 94 (11%) metformin, 307 (36%) metformin + statin, and 183 (22%) neither. Five-year BCR-free survival rates were 75% in metformin only versus 75% in metformin + statin versus 60% in statin versus 68% in no drug groups (log-rank, P = .003). On multivariable analysis, preoperative statin use was associated with increased BCR risk versus men receiving neither drug (hazard ratio [HR] = 1.84; 95% confidence interval [CI], 1.28-2.64). Metformin alone (HR 0.88; 95% CI, 0.53-1.47) and metformin + statin (HR 0.88; 95% CI, 0.58-1.33) were unrelated to BCR risks. In secondary analysis, the association between statin use and higher BCR risk was similar regardless of race, but was stronger among men with BMI ≥ 30 kg/m(2) (HR 3.12; 95% CI, 1.70-5.72). These results were largely unchanged after adjusting for HbA1c. 



CONCLUSION: Among diabetic men undergoing RP, preoperative statin use was associated with worse BCR risk, especially among men with a high BMI, but these associations may be mitigated by concomitant use of metformin. If validated in future findings, research is needed to understand the basis for these associations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12e9,

title = {Impact of prior local therapy on overall survival in men with metastatic castration-resistant prostate cancer: Results from Shared Equal Access Regional Cancer Hospital},

author = {D N Patel and S Jha and L E Howard and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and B F Chapin and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/30253446/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2018-2018&from_sort=pubdate&from_size=100&from_pos=6},

doi = {10.1111/iju.13806 },

isbn = {1442-2042},

year  = {2018},

date = {2018-12-01},

journal = {International journal of urology : official journal of the Japanese Urological Association},

volume = {25},

number = {12},

pages = {998-1004},

abstract = {OBJECTIVES: To evaluate the impact of previous local treatment on survival in men with newly diagnosed metastatic castration-resistant prostate cancer. 



METHODS: We carried out a retrospective study of patients newly diagnosed with metastatic castration-resistant prostate cancer in the year 2000 or later from eight Veterans Affairs Medical Centers. Patients were categorized based on prior local therapy (none, prostatectomy ± radiation or radiation alone). Overall and cancer-specific survival was estimated by the Kaplan-Meier method. Cox proportional hazards regression models were used to test the association between prior local treatment and survival. 



RESULTS: Of 729 patients, 284 (39%) underwent no local treatment, 176 (24%) underwent radical prostatectomy ± radiation and 269 (37%) underwent radiation alone. On multivariable analysis, men with prior prostatectomy had improved overall (hazard ratio 0.71, P = 0.005) and cancer-specific survival (hazard ratio 0.55, P < 0.001) compared with men with no prior local therapy. This improvement in overall (hazard ratio 0.89, P = 0.219) and cancer-specific survival (hazard ratio 0.87, P = 0.170) was not seen in men with prior radiation alone. After further adjusting for comorbidity with the Charlson Comorbidity Index, patients with prior prostatectomy still had improved overall survival (hazard ratio 0.70, P = 0.003), whereas this was not seen in patients who received prior radiation alone (hazard ratio 0.88, P = 0.185). 



CONCLUSIONS: Independent of patient- and disease-related factors, men with metastatic castration-resistant prostate cancer who had undergone prior radical prostatectomy have improved overall and cancer-specific survival compared with those with no prior local therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12ec,

title = {Radical prostatectomy and the effect of close surgical margins: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database},

author = {C Herforth and S P Stroup and Z Chen and L E Howard and S J Freedland and D M Moreira and M K Terris and W J Aronson and M R Cooperberg and C L Amling and C J Kane},

url = {https://pubmed.ncbi.nlm.nih.gov/29473992/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2018-2018&from_sort=pubdate&from_size=100&from_pos=9},

doi = {10.1111/bju.14178 },

isbn = {1464-410X},

year  = {2018},

date = {2018-10-01},

journal = {BJU international},

volume = {122},

number = {4},

pages = {592-598},

abstract = {OBJECTIVE: To evaluate biochemical recurrence (BCR) patterns amongst men undergoing radical prostatectomy (RP) with specimens having negative (NSM), positive (PSM), and close surgical margins (CSM) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons. 



PATIENTS AND METHODS: Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM, PSM, and CSM. CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate-specific antigen (PSA) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR, metastases, and mortality were analysed using Cox proportional hazard models. 



RESULTS: Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM, 1902 (44%) had PSM, and 372 (8%) had CSM. On multivariable analysis, relative to NSM, men with CSM had a higher risk of BCR (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.25-1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM (HR 2.09, 95% CI 1.86-2.36; P < 0.001). Metastases, prostate cancer-specific mortality and all-cause mortality did not differ based on margin status alone. 



CONCLUSIONS: Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12eb,

title = {Obese patients with castration-resistant prostate cancer may be at a lower risk of all-cause mortality: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database},

author = {A C Vidal and L E Howard and A de Hoedt and C J Kane and M K Terris and W J Aronson and M R Cooperberg and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/29521009/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2018-2018&from_sort=pubdate&from_size=100&from_pos=8},

doi = {10.1111/bju.14193 },

isbn = {1464-410X},

year  = {2018},

date = {2018-07-01},

journal = {BJU international},

volume = {122},

number = {1},

pages = {76-82},

abstract = {OBJECTIVE: To assess whether obesity is associated with progression to metastasis, prostate cancer-specific mortality (PCSM), and all-cause mortality (ACM), in patients with non-metastatic castration-resistant prostate cancer (non-mCRPC). At the population level, obesity is associated with prostate cancer mortality; however, some studies have found that higher body mass index (BMI) is associated with better long-term prostate cancer outcomes amongst men with mCRPC. 



PATIENTS AND METHODS: We identified 1 192 patients with non-mCRPC from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BMI was calculated from height and weight abstracted from the medical records at the time closest to but prior to CRPC diagnosis and categorised as underweight (<21 kg/m(2) ), normal weight (21-24.9 kg/m(2) ), overweight (25-29.9 kg/m(2) ), and obese (≥30 kg/m(2) ). Competing risks regression and Cox models were used to test associations between obesity and progression to metastasis, PCSM, and ACM, accounting for confounders. 



RESULTS: Overall, 51 (4%) men were underweight, 239 (25%) were normal weight, 464 (39%) were overweight, and 438 (37%) were obese. In adjusted analysis, higher BMI was significantly associated with reduced ACM (hazard ratio [HR] 0.98, P = 0.012) but not PCSM (HR 1.00, P = 0.737) or metastases (HR 0.99, P = 0.225). Likewise, when BMI was treated as a categorical variable in adjusted models, obesity was not associated with PCSM (HR 1.11, P = 0.436) or metastases (HR 1.06, P = 0.647), but was associated with decreased ACM (HR 0.79, P = 0.016) compared to normal weight. No data were available on treatments received after CRPC diagnosis.



CONCLUSIONS: Amongst patients with non-mCRPC obesity was associated with better overall survival. Although this result mirrors evidence from men with mCRPC, obesity was not associated with prostate cancer outcomes. Larger studies are needed to confirm these findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12ea,

title = {Neutrophil, lymphocyte and platelet counts, and risk of prostate cancer outcomes in white and black men: results from the SEARCH database},

author = {A C Vidal and L E Howard and A de Hoedt and M R Cooperberg and C J Kane and W J Aronson and M K Terris and C L Amling and E Taioli and J H Fowke and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/29663110/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2018-2018&from_sort=pubdate&from_size=100&from_pos=7},

doi = {10.1007/s10552-018-1031-2 },

isbn = {1573-7225},

year  = {2018},

date = {2018-06-01},

journal = {Cancer causes & control : CCC},

volume = {29},

number = {6},

pages = {581-588},

abstract = {PURPOSE: Systemic inflammation, as measured by C-reactive protein, has been linked with poor prostate cancer (PC) outcomes, predominantly in white men. Whether other immune measures like white blood cell counts are correlated with PC progression and whether results vary by race is unknown. We examined whether complete blood count (CBC) parameters were associated with PC outcomes and whether these associations varied by race. 



METHODS: Analyses include 1,826 radical prostatectomy patients from six VA hospitals followed through medical record review for biochemical recurrence (BCR). Secondary outcomes included castration-resistant PC (CRPC), metastasis, all-cause mortality (ACM), and PC-specific mortality (PCSM). Cox-proportional hazards were used to assess the associations between pre-operative neutrophils, lymphocytes, platelets, neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) with each outcome. We used a Bonferroni-corrected p-value of 0.05/5 = 0.01 as the threshold for statistical significance. 



RESULTS: Of 1,826 men, 794 (43%) were black and 1,032 (57%) white. Neutrophil count (p < 0.001), NLR (p < 0.001), and PLR (p < 0.001) were significantly lower, while lymphocyte count (p < 0.001) was significantly higher in black versus white men. After adjusting for clinicopathological features, no CBC measures were significantly associated with BCR. There were no interactions between CBC and race in predicting BCR. Similarly, no CBC values were significantly associated with CRPC, metastases, or PCSM either among all men or when stratified by race. However, higher neutrophil count was associated with higher ACM risk in white men (p = 0.004). 



CONCLUSION: Pre-operative CBC measures were not associated with PC outcomes in black or white men undergoing radical prostatectomy, except for neutrophils-positive association with risk of ACM in white men. Whether circulating immune cell markers provide insight to the pathophysiology of PC progression or adverse treatment outcomes requires further study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12ed,

title = {First postoperative PSA is associated with outcomes in patients with node positive prostate cancer: Results from the SEARCH database},

author = {M L McDonald and L E Howard and W J Aronson and M K Terris and M R Cooperberg and C L Amling and S J Freedland and C J Kane},

url = {https://pubmed.ncbi.nlm.nih.gov/29429895/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2018-2018&from_sort=pubdate&from_size=100&from_pos=10},

doi = {10.1016/j.urolonc.2018.01.005},

isbn = {1873-2496},

year  = {2018},

date = {2018-05-01},

journal = {Urologic oncology},

volume = {36},

number = {5},

pages = {239.e17-239.e25},

abstract = {OBJECTIVE: To analyze factors associated with metastases, prostate cancer-specific mortality, and all-cause mortality in pN1 patients. 



MATERIALS AND METHODS: We analyzed 3,642 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Pathologic Gleason grade, number of lymph nodes (LN) removed, and first postoperative prostate-specific antigen (PSA) (<0.2 ng/ml or ≥0.2 ng/ml) were among covariates assessed. Cox regression was used to analyze the association between characteristics and survival outcomes. Kaplan-Meier was used to estimate survival in pN1 patients stratified by first postoperative PSA. 



RESULTS: Of 3,642 patients, 124 (3.4%) had pN1. There were 71 (60%) patients with 1 positive LN, 32 (27%) with 2 positive LNs, and 15 (13%) with ≥3. Among men with pN1, first postoperative PSA was<0.2ng/ml in 46 patients (51%) and ≥0.2ng/ml in 44 patients (49%). Univariable Cox regression determined pathological Gleason grade (P = 0.021), seminal vesicle invasion (P = 0.010), and first postoperative PSA ≥0.2 ng/ml (P = 0.005) were associated with metastases. First postoperative PSA ≥0.2ng/ml was associated with metastasis on multivariable analysis (P = 0.046). Log-rank analysis revealed a more favorable metastases-free survival in patients with a first postoperative PSA<0.2ng/ml (P = 0.001). Estimated 5-year metastases-free survival rate was 99% for patients with a first postoperative PSA<0.2ng/ml and 87% for ≥0.2ng/ml. 



CONCLUSIONS: pN1 patients with a first postoperative PSA ≥0.2ng/ml were more likely to develop metastases. First postoperative PSA may be useful in identifying pN1 patients who harbor distant disease and aid in secondary treatment decisions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12ef,

title = {Does Early Prostate Specific Antigen Doubling Time after Radical Prostatectomy, Calculated Prior to Prostate Specific Antigen Recurrence, Correlate with Prostate Cancer Outcomes? A Report from the SEARCH Database Group},

author = {A E Teeter and K Griffin and L E Howard and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28870860/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2018-2018&from_sort=pubdate&from_size=100&from_pos=11},

doi = {10.1016/j.juro.2017.08.107},

isbn = {1527-3792},

year  = {2018},

date = {2018-03-01},

journal = {The Journal of urology},

volume = {199},

number = {3},

pages = {713-718},

abstract = {PURPOSE: Short prostate specific antigen doubling time following recurrence after radical prostatectomy portends a poor prognosis. Prostate specific antigen doubling time is traditionally calculated using prostate specific antigen values 0.2 ng/ml or greater. We determined whether early prostate specific antigen doubling time, calculated from the first detectable postoperative prostate specific antigen up to and including the first recurrence value, correlates with prostate cancer outcomes. 



MATERIALS AND METHODS: Cox models were used to examine the association between early prostate specific antigen doubling time and castration resistant prostate cancer, metastases, and all cause and prostate cancer specific mortality in 674 men who underwent radical prostatectomy between 1988 and 2014 and had a biochemical recurrence. Early prostate specific antigen doubling time was examined as a log transformed continuous and a categorical variable. 



RESULTS: After adjusting for multiple clinicopathological characteristics, log transformed early prostate specific antigen doubling time was not associated with any outcome. However, when early doubling time was categorized as 15 or greater, 9 to 14.9, 3 to 8.9 and less than 3 months, on multivariable analysis men with early doubling time less than 3 months were at increased risk for castration resistant prostate cancer (HR 6.20, p = 0.004), metastases (HR 5.26, p = 0.001), prostate cancer specific mortality (HR 5.06, p = 0.026) and all cause mortality (HR 1.63, p = 0.065) compared to those with an early doubling time of 15 months or greater. However, the association with all cause mortality was not significant. Those with an early prostate specific antigen doubling time of 3 to 8.9 months were at increased risk for castration resistant prostate cancer (HR 3.56, p = 0.015), all cause mortality (HR 1.67, p = 0.006) and prostate cancer specific mortality (HR 3.17, p = 0.044) but not metastases (p = 0.13).



CONCLUSIONS: Early prostate specific antigen doubling time less than 9 months, calculated using prostate specific antigen values before and up to biochemical recurrence, is associated with an increased risk of castration resistant prostate cancer, metastases, and prostate cancer specific and all cause mortality among men with biochemical recurrence after radical prostatectomy. Early prostate specific antigen doubling time allows for risk stratification at biochemical recurrence and before prostate specific antigen doubling time is calculable, enabling these men to be referred for early aggressive secondary treatment and/or clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12ee,

title = {Modified risk stratification grouping using standard clinical and biopsy information for patients undergoing radical prostatectomy: Results from SEARCH},

author = {Z S Zumsteg and Z Chen and L E Howard and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and D E Spratt and H M Sandler and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28994485/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=1},

doi = {10.1002/pros.23436 },

isbn = {1097-0045},

year  = {2017},

date = {2017-12-01},

journal = {The Prostate},

volume = {77},

number = {16},

pages = {1592-1600},

abstract = {INTRODUCTION: Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions. However, significant heterogeneity remains for those with unfavorable-risk disease. 



METHODS: This study included 3335 patients undergoing radical prostatectomy without adjuvant radiotherapy in the SEARCH database. High-risk patients were dichotomized into standard and very high-risk (VHR) groups based on primary Gleason pattern, percentage of positive biopsy cores (PPBC), number of NCCN high-risk factors, and stage T3b-T4 disease. Similarly, intermediate-risk prostate cancer was separated into favorable and unfavorable groups based on primary Gleason pattern, PPBC, and number of NCCN intermediate-risk factors. 



RESULTS: Median follow-up was 78 months. Patients with VHR prostate cancer had significantly worse PSA relapse-free survival (PSA-RFS, P < 0.001), distant metastasis (DM, P = 0.004), and prostate cancer-specific mortality (PCSM, P = 0.015) in comparison to standard high-risk (SHR) patients in multivariable analyses. By contrast, there was no significant difference in PSA-RFS, DM, or PCSM between SHR and unfavorable intermediate-risk (UIR) patients. Therefore, we propose a novel risk stratification system: Group 1 (low-risk), Group 2 (favorable intermediate-risk), Group 3 (UIR and SHR), and Group 4 (VHR). The c-index of this new grouping was 0.683 for PSA-RFS and 0.800 for metastases, compared to NCCN-risk groups which yield 0.666 for PSA-RFS and 0.764 for metastases. 



CONCLUSIONS: Patients classified as VHR have markedly increased rates of PSA relapse, DM, and PCSM in comparison to SHR patients, whereas UIR and SHR patients have similar prognosis. Novel therapeutic strategies are needed for patients with VHR, likely involving multimodality therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f1,

title = {Biopsy Detected Gleason Pattern 5 is Associated with Recurrence, Metastasis and Mortality in a Cohort of Men with High Risk Prostate Cancer},

author = {S P Stroup and D M Moreira and Z Chen and L Howard and J H Berger and M K Terris and W J Aronson and M R Cooperberg and C L Amling and C J Kane and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28709888/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=4},

doi = {10.1016/j.juro.2017.07.009},

isbn = {1527-3792},

year  = {2017},

date = {2017-12-01},

journal = {The Journal of urology},

volume = {198},

number = {6},

pages = {1309-1315},

abstract = {PURPOSE: We evaluated the relative risk of biochemical recurrence, metastasis and death from prostate cancer contributed by biopsy Gleason pattern 5 among men at high risk with Gleason 8-10 disease in the SEARCH (Shared Equal Access Regional Cancer Hospital) cohort. 



MATERIALS AND METHODS: Men with biopsy Gleason sum 8-10 prostate cancer treated with radical prostatectomy were evaluated. The cohort was divided into men with Gleason 4 + 4 vs those with any pattern 5 (ie Gleason 3 + 5, 5 + 3, 4 + 5, 5 + 4 or 5 + 5). Predictors of biochemical recurrence, metastases, and prostate cancer specific and overall survival were analyzed using Kaplan-Meier, log rank test and Cox proportional hazards models. 



RESULTS: We identified 634 men at high risk in the SEARCH database, of whom 394 (62%) had Gleason 4 + 4 and 240 (38%) had Gleason pattern 5 on biopsy. Baseline characteristics did not significantly differ between the groups. On multivariable analysis relative to Gleason 4 + 4 men at high risk with Gleason pattern 5 showed no difference in the risk of biochemical recurrence (HR 1.26, 95% CI 0.99-1.61, p = 0.065). However, they were at significantly greater risk for metastasis (HR 2.55, 95% CI 1.50-4.35, p = 0.001), prostate cancer specific mortality (HR 2.67, 95% CI 0.1.26-5.66, p = 0.010) and overall mortality (HR 1.60, 95% CI 1.09-2.34, p = 0.016).



CONCLUSIONS: Preoperative subclassification of high risk prostate cancer by biopsy Gleason grade (4 + 4 vs any Gleason pattern 5) identified men at highest risk for progression. Any Gleason 5 on biopsy is associated with a greater risk of metastasis, and prostate cancer specific and overall mortality. Grouping all Gleason 8-10 tumors together as high risk lesions may fail to fully stratify men at highest risk for poor outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f3,

title = {Validation of the 2015 prostate cancer grade groups for predicting long-term oncologic outcomes in a shared equal-access health system},

author = {A A Schulman and L E Howard and K J Tay and E Tsivian and C Sze and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and S J Freedland and T J Polascik},

url = {https://pubmed.ncbi.nlm.nih.gov/28662291/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=6},

doi = {10.1002/cncr.30844 },

isbn = {1097-0142},

year  = {2017},

date = {2017-11-01},

journal = {Cancer},

volume = {123},

number = {21},

pages = {4122-4129},

abstract = {BACKGROUND: A 5-tier prognostic grade group (GG) system was enacted to simplify the risk stratification of patients with prostate cancer in which Gleason scores of ≤6, 3 + 4, 4 + 3, 8, and 9 or 10 are considered GG 1 through 5, respectively. The authors investigated the utility of biopsy GG for predicting long-term oncologic outcomes after radical prostatectomy in an equal-access health system. 



METHODS: Men who underwent prostatectomy at 1 of 6 Veterans Affairs hospitals in the Shared Equal Access Regional Cancer Hospital database between 2005 and 2015 were reviewed. The prognostic ability of biopsy GG was examined using Cox models. Interactions between GG and race also were tested. 



RESULTS: In total, 2509 men were identified who had data available on biopsy Gleason scores, covariates, and follow-up. The cohort included men with GG 1 (909 patients; 36.2%), GG 2 (813 patients; 32.4%), GG 3 (398 patients; 15.9%), GG 4 (279 patients; 11.1%), and GG 5 (110 patients; 4.4%) prostate cancer. The cohort included 1002 African American men (41%). The median follow-up was 60 months (interquartile range, 33-90 months). Higher GG was associated with higher clinical stage, older age, more recent surgery, and surgical center (P < .001) as well as increased biochemical recurrence, secondary therapy, castration-resistant prostate cancer, metastases, and prostate cancer-specific mortality (all P < .001). There were no significant interactions with race in predicting measured outcomes. 



CONCLUSIONS: The 5-tier GG system predicted multiple long-term endpoints after radical prostatectomy in an equal-access health system. The predictive value was consistent across races. Cancer 2017;123:4122-4129. © 2017 American Cancer Society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f4,

title = {Race and risk of metastases and survival after radical prostatectomy: Results from the SEARCH database},

author = {S J Freedland and A C Vidal and L E Howard and M K Terris and M R Cooperberg and C L Amling and C J Kane and W J Aronson and Shared Equal Access Regional Cancer Hospital (SEARCH) Database Study Group},

url = {https://pubmed.ncbi.nlm.nih.gov/28654204/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=7},

doi = {10.1002/cncr.30834 },

isbn = {1097-0142},

year  = {2017},

date = {2017-11-01},

journal = {Cancer},

volume = {123},

number = {21},

pages = {4199-4206},

abstract = {BACKGROUND: Black race is associated with prostate cancer (PC) diagnosis and poor outcome. Previously, the authors reported that black men undergoing radical prostatectomy (RP) in equal-access hospitals had an increased risk of biochemical disease recurrence (BCR), but recurrences were equally aggressive as those occurring in white men. The authors examined the association between race and long-term outcomes after RP. 



METHODS: Data regarding 1665 black men (37%) and 2791 white men (63%) undergoing RP were analyzed. Using Cox models, the authors tested the association between race and BCR, BCR with a prostate-specific antigen (PSA) doubling time <9 months (aggressive disease recurrence), metastases, PC-specific death, and overall death. 



RESULTS: At a median follow-up of 102 months, 1566 men (35%) developed BCR, 217 men (5%) experienced aggressive disease recurrence, 193 men (4%) developed metastases, and 1207 men (27%) had died, 107 of whom (2%) died of PC. White men were older and had a lower preoperative PSA level, a lower biopsy and pathological grade group, and more capsular penetration but less seminal vesicle invasion and positive surgical margins versus black men (all P<.05). Black men were found to have a more recent surgery year (P<.001). On univariable analysis, black race was associated with increased BCR (P = .003) and reduced overall death (P = .017). On multivariable analysis, black race was not found to be associated with BCR (hazard ratio [HR], 1.07; P = .26), aggressive recurrence (HR, 1.14; P = .42), metastasis (HR, 1.24; P = .21), PC-specific death (HR, 1.03; P = .91), or overall death (HR, 1.03; P = .67). 



CONCLUSIONS: Among men undergoing RP at equal-access centers, although black men were found to have an increased risk of BCR, they had similar risks of aggressive disease recurrence, metastasis, and PC-specific death compared with white men, and the risk of BCR was found to be similar after controlling for risk parameters. Longer follow-up is needed to confirm these findings. Cancer 2017;123:4199-4206. © 2017 American Cancer Society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f6,

title = {Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer},

author = {L E Howard and D M Moreira and De A Hoedt and W J Aronson and C J Kane and C L Amling and M R Cooperberg and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28371163/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=9},

doi = {10.1111/bju.13856 },

isbn = {1464-410X},

year  = {2017},

date = {2017-11-01},

journal = {BJU international},

volume = {120},

number = {5B},

pages = {E80-E86},

abstract = {OBJECTIVES: To examine whether prostate-specific antigen doubling time (PSADT) correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer (CRPC). 



MATERIALS AND METHODS: We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios (HRs). 



RESULTS: The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM (HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases (HR 8.63, 95% CI 5.07-14.7) and PCSM (HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM (HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively. 



CONCLUSION: Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f0,

title = {Timing of Prostate-specific Antigen Nadir After Radical Prostatectomy and Risk of Biochemical Recurrence},

author = {S L Skove and L E Howard and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and D M Moreira and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28735016/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=3},

doi = {10.1016/j.urology.2017.07.009},

isbn = {1527-9995},

year  = {2017},

date = {2017-10-01},

journal = {Urology},

volume = {108},

pages = {129-134},

abstract = {OBJECTIVE: To evaluate the association between the prostate-specific antigen (PSA) nadir level and the time to nadir (TTN) with biochemical recurrence (BCR) risk after radical prostatectomy (RP) in the Shared Equal-Access Research Cancer Hospital (SEARCH) database. 



MATERIALS AND METHODS: This is a retrospective analysis of 1939 men from the SEARCH database treated with RP between 1998 and 2015 with available ultrasensitive PSA nadir within 1-6 months after RP. Uni- and multivariable analyses of PSA nadir and TTN with time from nadir to BCR were performed with Cox models (adjusted for demographics, tumor features, and preoperative PSA). 



RESULTS: Among men with an undetectable PSA nadir, the TTN was unrelated to BCR (1.0-2.9 vs 3-6 months: hazard ratio [HR] 0.86, P = .46). Regardless of TTN, men with detectable nadir had an increased risk of BCR (TTN of 3-6 months: HR 1.81, P = .024; TTN of 1.0-2.99 months: HR 3.75, P <.001 vs undetectable nadir and TTN of 3-6 months). Among men with a detectable PSA at 1-3 months, 53% had a lower PSA level during follow-up 3-6 months after RP, which was undetectable in 32% and lower but still detectable in 21%. 



CONCLUSION: In the post-RP setting, men with both a detectable nadir and a shorter TTN had an increased risk of BCR. Intriguingly, about half of the men with a detectable PSA in the first 3 months after RP had a lower PSA level during follow-up between 3 and 6 months after RP. If confirmed in future studies, this has important implications for patients considering adjuvant therapy based on postoperative PSA values in the first 3 months after RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12fa,

title = {In Men with Castration-Resistant Prostate Cancer, Visceral Metastases Predict Shorter Overall Survival: What Predicts Visceral Metastases? Results from the SEARCH Database},

author = {C A Whitney and L E Howard and E M Posadas and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28753787/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=14},

doi = {10.1016/j.euf.2016.08.007},

isbn = {2405-4569},

year  = {2017},

date = {2017-10-01},

journal = {European urology focus},

volume = {3},

number = {4-5},

pages = {480-486},

abstract = {BACKGROUND: Although visceral metastases (VMs) are widely recognized to portend worse prognoses compared with bone and lymph metastases in men with metastatic castration-resistant prostate cancer (mCRPC), little is known about what predicts VMs and the extent to which men with VMs do worse. 



OBJECTIVE: To determine whether men with VMs at initial mCRPC diagnosis have worse overall survival (OS) and identify predictors of VMs. 



DESIGN, SETTING, AND PARTICIPANTS: We analyzed 494 men diagnosed with castration-resistant prostate cancer post-1999 and no known metastases from five Veterans Affairs hospitals of the Shared Equal Access Regional Cancer Hospital (SEARCH) database who later developed metastases. Radiology scans within 30 d of initial metastasis diagnosis were reviewed to collect information on bone, visceral, and lymph node metastases. We analyzed the 236 men who had a computed tomography scan performed. 



OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Predictors of VMs and OS were evaluated using logistic regression and Cox models, respectively. 



RESULTS AND LIMITATIONS: Of the 236 mCRPC patients, 38 (16%) had VMs. Regarding VMs, 19 patients (50%), 8 patients (21%), and 16 patients (42%) had metastases in the liver, lungs, and other locations, respectively. VMs were a predictor of OS on crude analysis (hazard ratio [HR]: 1.88; 95% confidence interval [CI], 1.30-2.72; p=0.001) and after risk adjustment (HR: 1.84; 95% CI, 1.24-2.72; p=0.002). Age, year, treatment center, prostate-specific antigen (PSA), and time from CRPC to metastases were significant in predicting OS (all p 0.09). Prospective studies and larger cohorts are needed to validate our findings. 



CONCLUSIONS: Demographic, tumor, and PSA kinetic characteristics were not predictive of having VMs, but VMs predicted worse OS. 



PATIENT SUMMARY: Because patients with VMs have worse overall survival, further research is needed to develop better biomarkers and thus diagnose those with VMs at earlier stages in their disease course.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f2,

title = {Predictors of operative time during radical retropubic prostatectomy and robot-assisted laparoscopic prostatectomy},

author = {R M Simon and L E Howard and D M Moreira and M K Terris and C J Kane and W J Aronson and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28697533/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=5},

doi = {10.1111/iju.13393 },

isbn = {1442-2042},

year  = {2017},

date = {2017-08-01},

journal = {International journal of urology : official journal of the Japanese Urological Association},

volume = {24},

number = {8},

pages = {618-623},

abstract = {OBJECTIVES: To better predict operative time using patient/surgical characteristics among men undergoing radical retropubic prostatectomy or robot-assisted laparoscopic prostatectomy in order to achieve more efficient operative scheduling and potentially decrease costs in the Veterans Health System. 



METHODS: We analyzed 2619 men treated with radical retropubic prostatectomy (n = 2005) or robot-assisted laparoscopic prostatectomy (n = 614) from 1993 to 2013 from six Veterans Affairs Hospitals in the Shared Equal Access Regional Cancer Hospital database. Age, body mass index, race, biopsy Gleason, prostate weight, undergoing a nerve-sparing procedure or lymph node dissection, and hospital surgical volume were analyzed in multivariable linear regression to identify predictors of operative time and to quantify the increase/decrease observed. 



RESULTS: In men undergoing radical retropubic prostatectomy, body mass index, black race, prostate weight and a lymph node dissection all predicted longer operative times (all P ≤ 0.004). In men undergoing robot-assisted laparoscopic prostatectomy, biopsy Gleason score and a lymph node dissection were associated with increased operative time (P ≤ 0.048). In both surgical methods, a lymph node dissection added 25-40 min to the operation. Also, in both, each additional operation per year per center predicted a 0.80-0.89-min decrease in operative time (P ≤ 0.001). 



CONCLUSIONS: Overall, several factors seem to be associated with quantifiable changes in operative time. If confirmed in future studies, these findings can allow for a more precise estimate of operative time, which could decrease the overall cost to the patient and hospital by aiding in operating room time management.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f5,

title = {Characterization of a "Low-Risk" Cohort of Grade Group 2 Prostate Cancer Patients: Results From the Shared Equal Access Regional Cancer Hospital Database},

author = {K F McGinley and X Sun and L E Howard and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28589550/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=8},

doi = {10.1111/iju.13387 },

isbn = {1442-2042},

year  = {2017},

date = {2017-08-01},

journal = {International journal of urology : official journal of the Japanese Urological Association},

volume = {24},

number = {8},

pages = {611-617},

abstract = {OBJECTIVES: To examine if there is a subset of men with grade group 2 prostate cancer who could be potential candidates for active surveillance. 



METHODS: We used the Shared Equal Access Regional Cancer Hospital database to identify 776 men undergoing radical prostatectomy from 2006 to 2015 with >8 biopsy cores obtained and complete information. We compared men who fulfilled low-risk disease criteria (clinical stage T1c/T2a; grade group 1; prostate-specific antigen ≤10 ng/mL) with the exception of grade group 2 versus men who met all three low-risk criteria. Logistic regression was used to test the association between grade group and radical prostatectomy pathological features. Biochemical recurrence was examined using Cox models. To examine whether there was a subset of men with low-volume grade group 2 with comparable outcomes to low-risk men, we repeated all analyses limiting the percentage of positive cores in the grade group 2 group to ≤33%, and positive cores to ≤4, ≤3 or ≤2. 



RESULTS: Grade group 2 low-risk men had increased risk of pathological grade group 3 or higher (P 0.2), except higher pathological grade group (P = 0.006). Biochemical recurrence was similar in men in grade group 1 and grade group 2 (hazard ratio = 1.24; P = 0.529). 



CONCLUSIONS: Among men with prostate-specific antigen ≤10 ng/mL and clinical stage T1c/T2a, those in grade group 2 with ≤2 total positive cores have similar rates of adverse pathology and biochemical recurrence as men with grade group 1.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f7,

title = {Factors predicting skeletal-related events in patients with bone metastatic castration-resistant prostate cancer},

author = {Z Klaassen and L E Howard and A de Hoedt and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/28026865/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=10},

doi = {10.1002/cncr.30505 },

isbn = {1097-0142},

year  = {2017},

date = {2017-05-01},

journal = {Cancer},

volume = {123},

number = {9},

pages = {1528-1535},

abstract = {BACKGROUND: Skeletal-related events (SREs) are common complications of bone metastatic castration-resistant prostate cancer (mCRPC). To the authors' knowledge, there are limited data regarding which factors predict SREs. The authors identified risk factors for SREs in men with bone mCRPC using characteristics commonly available in the medical record. 



METHODS: Data from 454 patients with nonmetastatic CRPC were identified from 2 Veteran Affairs Medical Centers from 2000 through 2013. Among these men, 233 (51%) developed bone metastases during follow-up and represented the study cohort. First occurrence of an SRE was abstracted from the medical records. A stepwise multivariable Cox model was used to select the strongest predictors of time to SRE. 



RESULTS: The median age of the patients at the time of diagnosis of bone mCRPC was 75 years (interquartile range, 68-81 years), and there were 153 nonblack patients (66%). During follow-up (median, 7.8 months [interquartile range, 2.9-18.3 months]), 88 patients (38%) had an SRE. On univariable analysis, more recent year of metastasis (hazard ratio [HR], 0.91), prostate-specific antigen doubling time of ≥9 months versus <9 months (HR, 0.50), and bone pain (HR, 3.34) were all found to be associated with SRE risk. On multivariable analysis, year of metastasis (HR, 0.93), biopsy Gleason score of 7 versus ≤6 (HR, 1.74), radiotherapy as the primary localized treatment versus none (HR, 2.33), and bone pain (HR, 3.64) were associated with SRE risk. The area under the curve for a multivariable model based upon these risk factors was 0.744. 



CONCLUSIONS: The authors identified several significant predictors of SREs among men with mCRPC. In particular, men with bone pain are at high risk of an SRE. If confirmed, future trials should focus on prolonging life and reducing SRE risk in patients with mCRPC with bone pain. Cancer 2017;123:1528-1535. © 2017 American Cancer Society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f8,

title = {Number of Unfavorable Intermediate-Risk Factors Predicts Pathologic Upstaging and Prostate Cancer-Specific Mortality Following Radical Prostatectomy: Results From the SEARCH Database},

author = {Z S Zumsteg and Z Chen and L E Howard and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and D E Spratt and H M Sandler and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/27683213/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=12},

doi = {10.1002/pros.23255 },

isbn = {1097-0045},

year  = {2017},

date = {2017-02-01},

journal = {The Prostate},

volume = {77},

number = {2},

pages = {154-163},

abstract = {BACKGROUND: To validate and further improve the stratification of intermediate risk prostate cancer into favorable and unfavorable subgroups for patients undergoing radical prostatectomy. MATERIALS AND 



METHODS: The SEARCH database was queried for IR patients undergoing radical prostatectomy without adjuvant radiotherapy. UIR disease was defined any patient with at least one unfavorable risk factor (URF), including primary Gleason pattern 4, 50% of more biopsy cores containing cancer, or multiple National Comprehensive Cancer Network IR factors. 



RESULTS: One thousand five hundred eighty-six patients with IR prostate cancer comprised the study cohort. Median follow-up was 62 months. Patients classified as UIR were significantly more likely to have pathologic high-risk features, such as Gleason score 8 - 10, pT3-4 disease, or lymph node metastases, than FIR patients (P < 0.001). Furthermore, UIR patients had significantly higher rates of PSA-relapse (PSA, hazard ratio [HR] = 1.89, P < 0.001) and distant metastasis (DM, HR = 2.92, P = 0.001), but no difference in prostate cancer-specific mortality (PCSM) or all-cause mortality in multivariable analysis. On secondary analysis, patients with ≥2 URF had significantly worse PSA-RFS, DM, and PCSM than those with 0 or 1 URF. Moreover, 40% of patients with ≥2 URF had high-risk pathologic features. 



CONCLUSIONS: Patients with UIR prostate cancer are at increased risk of PSA relapse, DM, and pathologic upstaging following prostatectomy. However, increased risk of PCSM was only detected in those with ≥2 URF. This suggests that further refinement of the UIR subgroup may improve risk stratification. Prostate Prostate 77:154-163, 2017. © 2016 Wiley Periodicals, Inc.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12f9,

title = {Predicting Time From Metastasis to Overall Survival in Castration-Resistant Prostate Cancer: Results From SEARCH},

author = {D M Moreira and L E Howard and K N Sourbeer and H S Amarasekara and L C Chow and D C Cockrell and C L Pratson and B T Hanyok and W J Aronson and C J Kane and M K Terris and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/27692812/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2017-2017&from_sort=pubdate&from_size=100&from_pos=13},

doi = {10.1016/j.clgc.2016.08.018},

isbn = {1938-0682},

year  = {2017},

date = {2017-02-01},

journal = {Clinical genitourinary cancer},

volume = {15},

number = {1},

pages = {60-66.e2},

abstract = {OBJECTIVE: To identify the predictors of time from initial diagnosis of metastatic castration-resistance prostate cancer (mCRPC) to all-cause death within the Shared Equal Access Regional Cancer Hospital cohort. 



PATIENTS AND METHODS: We performed a retrospective analysis of 205 mCRPC men. Overall survival was estimated and plotted using the Kaplan-Meier method. The uni- and multivariable overall survival predictors were evaluated with the Cox proportional hazards model. A nomogram was generated to predict overall survival at 1, 2, 3, and 5 years after mCRPC. Concordance index and calibration plot were obtained. 



RESULTS: A total of 170 men (83%) died over a median follow-up of 41 months. In univariable analysis, older age, more remote year of mCRPC, nonblack race, greater number of bone metastasis, higher prostate-specific antigen (PSA) levels, shorter PSA doubling time, and faster PSA velocity at mCRPC diagnosis were significantly associated with shorter overall survival (all P < .05). In multivariable analysis, older age, more remote year of mCRPC, greater number of bone metastasis, higher PSA levels, and shorter PSA doubling time at mCRPC diagnosis remained significantly associated with shorter overall survival (all P < .05). On the basis of these variables, a nomogram was generated yielding a concordance index of 0.67 and good calibration. 



CONCLUSION: The use of clinical parameter such as age, disease burden, and PSA levels and kinetics can be used to estimate overall survival in mCRPC patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27698439,

title = {Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Ħospital (SEARCĦ) database},

author = {A C Vidal and L E Howard and S X Sun and M R Cooperberg and C J Kane and W J Aronson and M K Terris and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/27698439/?from_term=FREEDLAND+KANE&from_sort=pubdate&from_size=100&from_pos=37},

doi = {10.1038/pcan.2016.47},

year  = {2017},

date = {2017-01-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {20},

number = {1},

pages = {72--78},

abstract = {BACKGROUND: At the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment.



METHODS: We conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m2, overweight 25-29.9 kg/m2 and obese ⩾30 kg/m2). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk.



RESULTS: On crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant.



CONCLUSIONS: Overweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12fb,

title = {Race does not predict the development of metastases in men with nonmetastatic castration-resistant prostate cancer},

author = {C A Whitney and L E Howard and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/27505036/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=7},

doi = {10.1002/cncr.30221 },

isbn = {1097-0142},

year  = {2016},

date = {2016-12-01},

journal = {Cancer},

volume = {122},

number = {24},

pages = {3848-3855},

abstract = {BACKGROUND: Although race is associated with prostate cancer progression in early stage disease, once men have advanced disease, it is unclear whether race continues to predict a poor outcome. The authors hypothesized that, in an equal-access setting among patients with castration-resistant prostate cancer (CRPC) and no known metastases (M0/Mx), black men would receive imaging tests at similar rates as nonblack men (ie, there would be an equal opportunity to detect metastases) but would have a higher risk of metastatic disease. 



METHODS: In total, 837 men who were diagnosed with M0/Mx CRPC during 2000 through 2014 from 5 Veterans Affairs hospitals in the SEARCH (Shared Equal Access Regional Cancer Hospital) database were analyzed. Data on all imaging tests after CRPC diagnosis were collected, including date, type, and outcome. Multivariable Cox models were used to test associations between race and the time to first metastasis, first bone metastasis, first bone scan, second bone scan among men who had a negative first bone scan, and overall survival. 



RESULTS: Black men (n = 306) were equally as likely as nonblack men (n = 531) to receive a first and second bone scan after a diagnosis of CRPC. There were no significant differences in the risk of developing any metastases, bone metastases, time to bone scans, or overall survival between black men and nonblack men (all P > .2). 



CONCLUSIONS: The lack of racial differences in the development of metastases and scanning practices observed in this study suggests that, once men have a diagnosis of M0/Mx CRPC, race may not be a prognostic factor. Efforts to understand prostate cancer racial disparities may derive greater benefit by focusing on the risk of developing prostate cancer and on the outcomes of men who have early stage disease. Cancer 2016;122:3848-3855. © 2016 American Cancer Society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12fc,

title = {Pathological and Biochemical Outcomes among African-American and Caucasian Men with Low Risk Prostate Cancer in the SEARCH Database: Implications for Active Surveillance Candidacy},

author = {M S Leapman and S J Freedland and W J Aronson and C J Kane and M K Terris and K Walker and C L Amling and P R Carroll and M R Cooperberg},

url = {https://pubmed.ncbi.nlm.nih.gov/27352635/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=9},

doi = {10.1016/j.juro.2016.06.086},

isbn = {1527-3792},

year  = {2016},

date = {2016-11-01},

journal = {The Journal of urology},

volume = {196},

number = {5},

pages = {1408-1414},

abstract = {PURPOSE: Racial disparities in the incidence and risk profile of prostate cancer at diagnosis among African-American men are well reported. However, it remains unclear whether African-American race is independently associated with adverse outcomes in men with clinical low risk disease. 



MATERIALS AND METHODS: We retrospectively analyzed the records of 895 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database in whom clinical low risk prostate cancer was treated with radical prostatectomy. Associations of African-American and Caucasian race with pathological biochemical recurrence outcomes were examined using chi-square, logistic regression, log rank and Cox proportional hazards analyses. 



RESULTS: We identified 355 African-American and 540 Caucasian men with low risk tumors in the SEARCH cohort who were followed a median of 6.3 years. Following adjustment for relevant covariates African-American race was not significantly associated with pathological upgrading (OR 1.33, p = 0.12), major upgrading (OR 0.58, p = 0.10), up-staging (OR 1.09, p = 0.73) or positive surgical margins (OR 1.04, p = 0.81). Five-year recurrence-free survival rates were 73.4% in African-American men and 78.4% in Caucasian men (log rank p = 0.18). In a Cox proportional hazards analysis model African-American race was not significantly associated with biochemical recurrence (HR 1.11, p = 0.52).



CONCLUSION: In a cohort of patients at clinical low risk who were treated with prostatectomy in an equal access health system with a high representation of African-American men we observed no significant differences in the rates of pathological upgrading, up-staging or biochemical recurrence. These data support continued use of active surveillance in African-American men. Upgrading and up-staging remain concerning possibilities for all men regardless of race.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12fd,

title = {Predictors of Time to Metastasis in Castration-resistant Prostate Cancer},

author = {D M Moreira and L E Howard and K N Sourbeer and H S Amarasekara and L C Chow and D C Cockrell and B T Hanyok and W J Aronson and C J Kane and M K Terris and C L Amling and M R Cooperberg and A Liede and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/27318265/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=10},

doi = {10.1016/j.urology.2016.06.011},

isbn = {1527-9995},

year  = {2016},

date = {2016-10-01},

journal = {Urology},

volume = {96},

pages = {171-176},

abstract = {OBJECTIVE: To investigate predictors of time to metastasis among men treated with androgen deprivation therapy for nonmetastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital cohort.



METHODS: This is a retrospective analysis of 458 nonmetastatic CRPC men. Metastases were detected in routine bone scans or other imaging tests. Predictors of time to metastasis were analyzed using proportional hazards model with CRPC as time zero. 



RESULTS: A total of 256 (56%) men were diagnosed with metastatic disease over a median follow-up of 36 months. Metastasis-free survival was 79%, 65%, 52%, 47%, and 41% at 1, 2, 3, 4, and 5 years after CRPC, respectively. In multivariable analysis, Gleason score 8-10 (hazard ratio [HR] = 1.61; P = .026), receiving primary localized treatment (HR = 1.38; P = .028), higher prostate-specific antigen (PSA) levels at CRPC diagnosis (logPSA HR = 1.64; P < .001), and PSA doubling time ≤6 months (HR = 1.42; P = .040) were independently associated with shorter time to metastasis. Race, year of CRPC, age, and time from androgen deprivation therapy to CRPC were not associated with metastasis. 



CONCLUSION: Among nonmetastatic CRPC men, nearly 60% developed metastatic disease during the first 5 years, with most of the metastasis occurring within the first 3 years. Higher Gleason score, receiving primary treatment, higher PSA, and shorter PSA doubling time were independently associated with shorter time to metastasis. Therefore, these variables can be used to stratify patients according to metastasis risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12fe,

title = {Validation of a bone scan positivity risk table in non-metastatic castration-resistant prostate cancer},

author = {S J Freedland and L E Howard and B T Hanyok and V K Kadiyala and J Y Kuang and C A Whitney and F R Wilks and C J Kane and M K Terris and C L Amling and M R Cooperberg and W J Aronson and D M Moreira},

url = {https://pubmed.ncbi.nlm.nih.gov/26762961/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=11},

doi = {10.1111/bju.13405 },

isbn = {1464-410X},

year  = {2016},

date = {2016-10-01},

journal = {BJU international},

volume = {118},

number = {4},

pages = {570-577},

abstract = {OBJECTIVES: To test the external validity of a previously developed risk table, designed to predict the probability of a positive bone scan among men with non-metastatic (M0) castration-resistant prostate cancer (CRPC), in a separate cohort. 



PATIENTS AND METHODS: We retrospectively analysed 429 bone scans of 281 patients with CRPC, with no known previous metastases, treated at three Veterans Affairs Medical Centers. We assessed the predictors of a positive scan using generalized estimating equations. Area under the curve (AUC), calibration plots and decision-curve analysis were used to assess the performance of our previous model to predict a positive scan in the current data. 



RESULTS: A total of 113 scans (26%) were positive. On multivariable analysis, the only significant predictors of a positive scan were log-transformed prostate-specific antigen (PSA): hazard ratio (HR) 2.13; 95% confidence interval (CI) 1.71-2.66 (P < 0.001) and log-transformed PSA doubling time (PSADT): HR 0.53; 95% CI 0.41-0.68 (P < 0.001). Among men with a PSA level <5 ng/mL, the rate of positive scans was 5%. The previously developed risk table had an AUC of 0.735 to predict positive bone scan with excellent calibration, and provided additional net benefit in the decision-curve analysis. 



CONCLUSION: We have validated our previously developed table to predict the risk of a positive bone scan among men with M0/Mx CRPC. Use of this risk table may allow better tailoring of patients' scanning to identify metastases early, while minimizing over-imaging. Regardless of PSADT, positive bone scans were rare in men with a PSA <5 ng/mL.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1302,

title = {Do all men with pathological Gleason score 8-10 prostate cancer have poor outcomes? Results from the SEARCH database},

author = {S Fischer and D Lin and R M Simon and L E Howard and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and S J Freedland and A C Vidal},

url = {https://pubmed.ncbi.nlm.nih.gov/26351095/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=15},

doi = {10.1111/bju.13319 },

isbn = {1464-410X},

year  = {2016},

date = {2016-08-01},

journal = {BJU international},

volume = {118},

number = {2},

pages = {250-257},

abstract = {OBJECTIVE: To determine whether there are subsets of men with pathological high grade prostate cancer (Gleason score 8-10) with particularly high or low 2-year biochemical recurrence (BCR) risk after radical prostatectomy (RP) when stratified into groups based on combinations of pathological features, such as surgical margin status, extracapsular extension (ECE) and seminal vesicle invasion (SVI). 



MATERIALS AND METHODS: We identified 459 men treated with RP with pathological Gleason score 8-10 prostate cancer in the SEARCH database. The men were stratified into five groups based on pathological characteristics: group 1, men with negative surgical margins (NSMs) and no ECE; group 2, men with positive surgical margin (PSMs) and no ECE; group 3, men with NSMs and ECE; group 4, men with PSMs and ECE; and group 5, men with SVI. Cox proportional hazards models and the log-rank test were used to compare BCR among the groups. 



RESULTS: At 2 years after RP, pathological group was significantly correlated with BCR (log-rank, P < 0.001) with patients in group 5 (+SVI) having the highest BCR risk (66%) and those in group 1 (NSMs and no ECE) having the lowest risk (14%). When we compared groups 2, 3, and 4, with each other, there was no significant difference in BCR among the groups (~50% 2-year BCR risk; log-rank P = 0.28). Results were similar when adjusting for prostate-specific antigen, age, pathological Gleason sum and clinical stage, or after excluding men who received adjuvant therapy. 



CONCLUSIONS: In patients with high grade (Gleason score 8-10) prostate cancer after RP, the presence of either PSMs, ECE or SVI was associated with an increased risk of early BCR, with a 2-year BCR risk of ≥50%. Conversely, men with organ-confined margin-negative disease had a very low risk of early BCR despite Gleason score 8-10 disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1304,

title = {Adverse pathology and undetectable ultrasensitive prostate-specific antigen after radical prostatectomy: is adjuvant radiation warranted?},

author = {R M Simon and L E Howard and S J Freedland and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and A C Vidal},

url = {https://pubmed.ncbi.nlm.nih.gov/26010251/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=16},

doi = {10.1111/bju.13182 },

isbn = {1464-410X},

year  = {2016},

date = {2016-06-01},

journal = {BJU international},

volume = {117},

number = {6},

pages = {897-903},

abstract = {OBJECTIVES: To determine if men with adverse pathology but undetectable ultrasensitive (<0.01 ng/mL) PSA are at high-risk for biochemical recurrence (BCR), or if there is a subset of patients at low-risk for whom the benefit of adjuvant radiation therapy might be limited. 



PATIENTS AND METHODS: We evaluated 411 patients treated with RP from 2001 to 2013 without adjuvant radiation who had an undetectable (<0.01 ng/mL) PSA level after RP but with adverse pathology [positive surgical margins (PSMs), extraprostatic extension (EPE), and/or seminal vesicle invasion (SVI)]. Multivariable Cox regression analyses tested the relationship between pathological characteristics and BCR to identify groups of men at highest risk of early BCR. 



RESULTS: On multivariable analysis, only pathological Gleason 7 (4 + 3), Gleason ≥8, and SVI independently predicted BCR (P = 0.019, P < 0.001, and P = 0.001, respectively), although on two-way analysis men with Gleason 7 (4 + 3) did not have significantly higher rates of BCR compared with patients with Gleason ≤6 (log-rank, P = 0.074). Men with either Gleason ≥8 (with PSMs or EPE) or SVI (15% of the cohort) defined a high-risk group vs men without these characteristics (3-year BCR risk of 50.4% vs 11.9%, log-rank, P < 0.001).



CONCLUSIONS: Among men with adverse pathology but an undetectable (<0.01 ng/mL) PSA level after RP, the benefits of adjuvant radiation are probably limited except for men with Gleason 8-10 (with PSMs or EPE) or SVI who are at high-risk of early BCR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea398e4b07076c88e12ff,

title = {Racial Differences in the Association Between Preoperative Serum Cholesterol and Prostate Cancer Recurrence: Results from the SEARCH Database},

author = {E H Allott and L E Howard and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/26809276/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=12},

doi = {10.1158/1055-9965.EPI-15-0876 },

isbn = {1538-7755},

year  = {2016},

date = {2016-03-01},

journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},

volume = {25},

number = {3},

pages = {547-554},

abstract = {BACKGROUND: Black men are disproportionately affected by both cardiovascular disease and prostate cancer. Epidemiologic evidence linking dyslipidemia, an established cardiovascular risk factor, and prostate cancer progression is mixed. As existing studies were conducted in predominantly non-black populations, research on black men is lacking. 



METHODS: We identified 628 black and 1,020 non-black men who underwent radical prostatectomy and never used statins before surgery in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Median follow-up was 2.9 years. The impact of preoperative hypercholesterolemia on risk of biochemical recurrence was examined using multivariable, race-stratified proportional hazards. In secondary analysis, we examined associations with low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides, overall and among men with dyslipidemia. 



RESULTS: High cholesterol was associated with increased risk of recurrence in black [HR(per10 mg/dL) 1.06; 95% confidence interval (CI), 1.02-1.11] but not non-black men (HR(per10 mg/dL) 0.99; 95% CI, 0.95-1.03; P(interaction) = 0.011). Elevated triglycerides were associated with increased risk in both black and non-black men (HR(per10 mg/dL) 1.02; 95% CI, 1.00-1.03 and 1.02; 95% CI, 1.00-1.02, respectively; P(interaction) = 0.458). There were no significant associations between LDL or HDL and recurrence risk in either race. Associations with cholesterol, LDL, and triglycerides were similar among men with dyslipidemia, but low HDL was associated with increased risk of recurrence in black, but not non-black men with dyslipidemia (P(interaction) = 0.047). 



CONCLUSION: Elevated cholesterol was a risk factor for recurrence in black but not non-black men, whereas high triglycerides were associated with increased risk regardless of race. IMPACT: Significantly contrasting associations by race may provide insight into prostate cancer racial disparities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1300,

title = {Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital database},

author = {K F McGinley and X Sun and L E Howard and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/26667212/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=13},

doi = {10.1111/iju.13027 },

isbn = {1442-2042},

year  = {2016},

date = {2016-03-01},

journal = {International journal of urology : official journal of the Japanese Urological Association},

volume = {23},

number = {3},

pages = {241-246},

abstract = {OBJECTIVE: To evaluate performance of pelvic lymph node dissection during radical prostatectomy within an equal access care setting over a period of time, and stratified by prostate cancer risk group and surgical technique. 



METHODS: We identified men in the Shared Equal Access Regional Cancer Hospital database who had open or robotic-assisted radical prostatectomy from 2006 to 2013. Univariable logistic regression was used to test the association between age, race, body mass index, total biopsy cores, number of positive biopsy cores, risk group, year, center, surgical volume and surgical technique on pelvic lymph node dissection use. Multivariable logistic analysis was used to examine surgical technique and pelvic lymph node dissection performance. Spearman's correlation examined temporal changes in pelvic lymph node dissection utilization stratified by risk group and surgical technique. 



RESULTS: A total of 1425 men met inclusion criteria; 67% of them underwent pelvic lymph node dissection. On multivariable analysis, robotic-assisted radical prostatectomy was associated with an 92% decreased use of pelvic lymph node dissection in low-risk, 84% decreased in intermediate-risk and 91% decreased in high-risk men (all P < 0.001). In robotic-assisted radical prostatectomy, there was a trend for increased pelvic lymph node dissection utilization over time in high-risk men (Spearman; P = 0.077) reaching ~85% in 2012-2013, which was accompanied by increased use in low-risk men (P = 0.016). For open radical prostatectomy, fewer pelvic lymph node dissections were carried out in low-risk men over time, decreasing to ~35% (P = 0.047) in 2012-2013, whereas rates remained high for high-risk men throughout (~95%; P = 0.621). 



CONCLUSION: Regardless of risk group, pelvic lymph node dissection is carried out significantly less during robotic-assisted radical prostatectomy. For robotic-assisted radical prostatectomy, pelvic lymph node dissection utilization increased over time for high-risk men, but rates also increased for low-risk men. Further attention to the discrepancy between provided and guideline recommended pelvic lymph node dissection performance is required to improve prostate cancer care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1305,

title = {Positive surgical margins in radical prostatectomy patients do not predict long-term oncological outcomes: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort},

author = {P Mithal and L E Howard and W J Aronson and M K Terris and M R Cooperberg and C J Kane and C Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/26010160/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=17},

doi = {10.1111/bju.13181 },

isbn = {1464-410X},

year  = {2016},

date = {2016-02-01},

journal = {BJU international},

volume = {117},

number = {2},

pages = {244-248},

abstract = {OBJECTIVE: To assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM). 



PATIENTS AND METHODS: Retrospective study of 4,051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting biochemical recurrence (BCR), CRPC, metastases, and PCSM. To determine if PSMs were more predictive in certain patients, analyses were stratified by pathological Gleason score, stage, and preoperative prostate-specific antigen (PSA) level. 



RESULTS: The median (interquartile range) follow-up was 6.6 (3.2-10.6) years and 1 127 patients had >10 years of follow-up. During this time, 302 (32%) men had BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died from prostate cancer. There were 1,600 (40%) men with PSMs. In unadjusted models, PSMs were significantly associated with all adverse outcomes: BCR, CRPC, metastases and PCSM (all P ≤ 0.001). After adjusting for demographic and pathological characteristics, PSMs were associated with increased risk of only BCR (HR 1.98, P 0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA level, and when patients who underwent adjuvant radiotherapy were excluded. 



CONCLUSIONS: PSMs after RP are not an independent risk factor for CRPC, metastasis, or PCSM overall or within any subset. In the absence of other high-risk features, PSMs alone may not be an indication for adjuvant radiotherapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1301,

title = {Is computed tomography a necessary part of a metastatic evaluation for castration-resistant prostate cancer? Results from the Shared Equal Access Regional Cancer Hospital Database},

author = {B T Hanyok and L E Howard and C L Amling and W J Aronson and M R Cooperberg and C J Kane and M K Terris and E M Posadas and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/26484853/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2016-2016&from_sort=pubdate&from_size=100&from_pos=14},

doi = {10.1002/cncr.29748 },

isbn = {1097-0142},

year  = {2016},

date = {2016-01-01},

journal = {Cancer},

volume = {122},

number = {2},

pages = {222-229},

abstract = {BACKGROUND: Metastatic lesions in prostate cancer beyond the bone have prognostic importance and affect clinical therapeutic decisions. Few data exist regarding the prevalence of soft-tissue metastases at the initial diagnosis of metastatic castration-resistant prostate cancer (mCRPC). 



METHODS: This study analyzed 232 men with nonmetastatic (M0) castration-resistant prostate cancer (CRPC) who developed metastases detected by a bone scan or computed tomography (CT). All bone scans and CT scans within the 30 days before or after the mCRPC diagnosis were reviewed. The rate of soft-tissue metastases among those undergoing CT was determined. Then, predictors of soft-tissue metastases and visceral and lymph node metastases were identified. 



RESULTS: Compared with men undergoing CT (n = 118), men undergoing only bone scans (n = 114) were more likely to have received primary treatment (P = .048), were older (P = .013), and less recently developed metastases (P = .018). Among those undergoing CT, 52 (44%) had soft-tissue metastases, including 20 visceral metastases (17%) and 41 lymph node metastases (35%), whereas 30% had no bone involvement. In a univariable analysis, only prostate-specific antigen (PSA) predicted soft-tissue metastases (odds ratio [OR], 1.27; P = .047), and no statistically significant predictors of visceral metastases were found. A higher PSA level was associated with an increased risk of lymph node metastases (OR, 1.38; P = .014), whereas receiving primary treatment was associated with decreased risk (OR, 0.36; P = .015). 



CONCLUSIONS: The data suggest that there is a relatively high rate of soft-tissue metastasis (44%) among CRPC patients undergoing CT at the initial diagnosis of metastases, including some men with no bone involvement. Therefore, forgoing CT during a metastatic evaluation may lead to an underdiagnosis of soft-tissue metastases and an underdiagnosis of metastases in general. Cancer 2015. © 2015 American Cancer Society. Cancer 2016;122:222-229. © 2015 American Cancer Society.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27698440,

title = {Long-term oncological outcomes of apical positive surgical margins at radical prostatectomy in the Shared Equal Access Regional Cancer Ħospital cohort},

author = {H Wadhwa and M K Terris and W J Aronson and C J Kane and C L Amling and M R Cooperberg and S J Freedland and M R Abern},

url = {https://pubmed.ncbi.nlm.nih.gov/27698440/?from_term=FREEDLAND+KANE&from_sort=pubdate&from_size=100&from_pos=36},

doi = {10.1038/pcan.2016.45},

year  = {2016},

date = {2016-01-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {19},

number = {4},

pages = {423--428},

abstract = {BACKGROUND: Approximately 29-38% of all positive surgical margins (PSMs) at radical prostatectomy (RP) involve the apex. The prognostic significance of apical PSM remains unclear. We therefore compared the long-term oncologic outcomes of men with apical PSMs to those with negative PSMs, apical and other PSMs, and other PSMs at RP.



METHODS: The SEARCH (Shared Equal Access Regional Cancer Hospital) database was used to identify 4031 men with prostate cancer (PCa) managed with RP with complete pathologic grade and stage data. Margin status was categorized as negative, apex only, or other positive. Multivariable Cox regression models adjusted for pathologic stage and grade were developed to test the relationship between margin status and biochemical recurrence (BCR), metastases and PCa death.



RESULTS: In the final cohort, 34.3% had PSMs, whereas 65.7% had negative margins. Univariable analysis showed that compared with negative margins, apex-only PSM was associated with BCR (hazard ratio (HR): 1.4 [1.1-1.8]), but not metastases or PCa death, whereas apex and other PSMs were associated with BCR (HR: 3.3 [2.8-4]) and metastases (HR: 1.8 [1.02-3.1]) but not PCa death. Nonapical PSMs were associated with BCR (HR: 2.7 [2.4-3.1]), metastases (1.7 [1.2-2.5)] and PCa death (1.8 [1.05-3]). On multivariable analysis, apex-only, apex and other, and nonapical PSMs were associated with BCR but margin status was not associated with metastases or PCa death.



CONCLUSIONS: In a large cohort of men undergoing RP, those with PSMs at the prostatic apex had lower BCR, metastases, or PCa death compared with those with PSMs at other locations. When adjusted for pathologic stage and grade, however, PSMs were associated with BCR but not long-term oncologic outcomes. These data confirm that men with apex-only PSMs may not be ideal candidates for adjuvant therapy after RP.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid27377207,

title = {Đo skeletal-related events predict overall survival in men with metastatic castration-resistant prostate cancer?},

author = {L E Howard and A M De Hoedt and W J Aronson and C J Kane and C L Amling and M R Cooperberg and M K Terris and C H Divers and A Valderrama and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/27377207/?from_term=FREEDLAND+KANE&from_sort=pubdate&from_size=100&from_pos=42},

doi = {10.1038/pcan.2016.26},

year  = {2016},

date = {2016-01-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {19},

number = {4},

pages = {380--384},

abstract = {BACKGROUND: Skeletal-related events (SREs) including pathologic fracture, spinal cord compression, radiation to bone and surgery to bone, are common in men with bone metastatic castration-resistant prostate cancer (mCRPC). Men with mCRPC are at high risk of death. Whether SREs predict mortality is unclear. We tested the association between SREs and overall survival (OS) in a multiethnic cohort with bone mCRPC, controlling for key covariates unavailable in claims data such as bone pain, number of bone metastases and PSA doubling time (PSADT).



METHODS: We collected data on 233 men diagnosed with nonmetastatic castration-resistant prostate cancer (CRPC) in 2000-2013 at two Veterans Affairs hospitals who later progressed to bone metastases. First occurrence of SRE and OS were collected from the medical records. Cox models were used to test the association between SRE and OS, treating SRE as a time-dependent variable. We adjusted for age, year, race, treatment center, biopsy Gleason, primary treatment to the prostate, PSA, PSADT, months from androgen deprivation therapy to CRPC, months from CRPC to metastasis and number of bone metastases at initial bone metastasis diagnosis. In a secondary analysis, we also adjusted for bone pain.



RESULTS: During follow-up, 88 (38%) patients had an SRE and 198 (85%) died. After adjusting for risk factors, SRE was associated with increased mortality (hazard ratio (HR)=1.67; 95% confidence interval (CI) 1.22-2.30; P=0.001). When bone pain was added to the model, the association of SREs and OS was attenuated, but remained significant (HR=1.42; 95% CI 1.01-1.99; P=0.042).



CONCLUSIONS: SREs are associated with increased mortality in men with bone mCRPC. Further studies on the impact of preventing SREs to increase survival are warranted.

},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1303,

title = {Does larger tumor volume explain the higher prostate specific antigen levels in black men with prostate cancer--Results from the SEARCH database},

author = {Z Klaassen and L Howard and M K Terris and W J Aronson and M R Cooperberg and C L Amling and C J Kane and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/26452418/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2015-2015&from_sort=pubdate&from_size=100&from_pos=4},

doi = {10.1016/j.canep.2015.09.007},

isbn = {1877-783X},

year  = {2015},

date = {2015-12-01},

journal = {Cancer epidemiology},

volume = {39},

number = {6},

pages = {1066-1070},

abstract = {OBJECTIVES: To assess whether larger tumor volume in black men explains higher presurgical PSA levels versus white men with prostate cancer. 



METHODS: We retrospectively analyzed 1904 men from the Shared Equal Access Regional Cancer Hospital database who underwent radical prostatectomy from 1990 to 2013. Geometric mean of tumor volume and preoperative PSA for each race were estimated from multivariable linear regression models.



RESULTS: There were 1104 (58%) white men and 800 (42%) black men. Black men were younger (60.2 vs. 62.9 years, p<0.001) had a higher PSA (6.7 vs. 6.0 ng/mL, p<0.001), more positive margins (47 vs. 38%, p<0.001), and seminal vesicle invasion (13 vs. 9%, p=0.007). White patients had higher clinical stage (p<0.001) and greater median tumor volume (6.0 vs. 5.3 gm, p=0.011). After multivariable adjustment (except for PSA), white men had smaller mean tumor volumes (5.2 vs. 5.8 gm, p=0.011). When further adjusted for PSA, there was no racial difference in mean tumor volume (p=0.34). After multivariable adjustment, black men had higher mean PSAs vs. white men (7.5 vs. 6.1 ng/mL, p<0.001). Results were similar after further adjusting for tumor volume: black men had 16% higher mean PSAs versus white men (7.4 vs. 6.2 ng/mL, p<0.001).



CONCLUSIONS: In this study of men undergoing radical prostatectomy at multiple equal access medical centers, racial differences in tumor volume did not explain higher presurgical PSA levels in black versus white men. The exact reason for higher PSA values in black men remains unclear.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26171882,

title = {Predicting bone scan positivity in non-metastatic castration-resistant prostate cancer},

author = {D M Moreira and L E Howard and K N Sourbeer and H S Amarasekara and L C Chow and D C Cockrell and B T Hanyok and C L Pratson and W J Aronson and C J Kane and M K Terris and C L Amling and M R Cooperberg and A Liede and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/26171882/?from_term=FREEDLAND+KANE&from_sort=pubdate&from_size=100&from_pos=55},

doi = {10.1038/pcan.2015.25},

year  = {2015},

date = {2015-12-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {18},

number = {4},

pages = {333--337},

abstract = {Background: To evaluate PSA levels and kinetic cutoffs to predict positive bone scans for men with non-metastatic castration-resistant prostate cancer (CRPC) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.



Methods: Retrospective analysis of 531 bone scans of 312 clinically CRPC patients with no known metastases at baseline treated with a variety of primary treatment types in the SEARCH database. The association of patients' demographics, pathological features, PSA levels and kinetics with risk of a positive scan was tested using generalized estimating equations.



Results: A total of 149 (28%) scans were positive. Positive scans were associated with younger age (odds ratio (OR)=0.98; P=0.014), higher Gleason scores (relative to Gleason 2-6, Gleason 3+4: OR=2.03, P=0.035; Gleason 4+3 and 8-10: OR=1.76, P=0.059), higher prescan PSA (OR=2.11; P<0.001), shorter prescan PSA doubling time (PSADT; OR=0.53; P<0.001), higher PSA velocity (OR=1.74; P<0.001) and more remote scan year (OR=0.92; P=0.004). Scan positivity was 6, 14, 29 and 57% for men with PSA<5, 5-14.9, 15-49.9 and ⩾ 50 ng ml(-1), respectively (P-trend <0.001). Men with PSADT ⩾ 15, 9-14.9, 3-8.9 and <3 months had a scan positivity of 11, 22, 34 and 47%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the likelihood of a positive bone scan.



Conclusions: PSA levels and kinetics were associated with positive bone scans. We developed tables to predict the risk of positive bone scans by PSA and PSADT. Combining PSA levels and kinetics may help select patients with CRPC for bone scans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid26544944,

title = {Ŧhe Molecular Ŧaxonomy of Primary Prostate Cancer},

url = {https://pubmed.ncbi.nlm.nih.gov/26544944/?from_term=FREEDLAND+KANE&from_sort=pubdate&from_size=100&from_pos=48},

doi = {10.1016/j.cell.2015.10.025},

year  = {2015},

date = {2015-11-01},

journal = {Cell},

volume = {163},

number = {4},

pages = {1011--1025},

abstract = {There is substantial heterogeneity among primary prostate cancers, evident in the spectrum of molecular abnormalities and its variable clinical course. As part of The Cancer Genome Atlas (TCGA), we present a comprehensive molecular analysis of 333 primary prostate carcinomas. Our results revealed a molecular taxonomy in which 74% of these tumors fell into one of seven subtypes defined by specific gene fusions (ERG, ETV1/4, and FLI1) or mutations (SPOP, FOXA1, and IDH1). Epigenetic profiles showed substantial heterogeneity, including an IDH1 mutant subset with a methylator phenotype. Androgen receptor (AR) activity varied widely and in a subtype-specific manner, with SPOP and FOXA1 mutant tumors having the highest levels of AR-induced transcripts. 25% of the prostate cancers had a presumed actionable lesion in the PI3K or MAPK signaling pathways, and DNA repair genes were inactivated in 19%. Our analysis reveals molecular heterogeneity among primary prostate cancers, as well as potentially actionable molecular defects.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1306,

title = {Agent Orange and long-term outcomes after radical prostatectomy},

author = {A E Ovadia and M K Terris and W J Aronson and C J Kane and C L Amling and M R Cooperberg and S J Freedland and M R Abern},

url = {https://pubmed.ncbi.nlm.nih.gov/25998746/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2015-2015&from_sort=pubdate&from_size=100&from_pos=8},

doi = {10.1016/j.urolonc.2015.04.012},

isbn = {1873-2496},

year  = {2015},

date = {2015-07-01},

journal = {Urologic oncology},

volume = {33},

number = {7},

pages = {329.e1-329.e6},

abstract = {PURPOSE: To investigate the association between Agent Orange (AO) exposure and long-term prostate cancer (PC) outcomes. 



MATERIAL AND METHODS: Data from 1,882 men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans Affairs Health Care Facilities were analyzed from the Shared Equal Access Regional Cancer Hospital database. Men were stratified by AO exposure (binary). Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and pathologic stage were determined by logistic regression models adjusted for preoperative characteristics. Hazard ratios for biochemical recurrence (BCR), secondary treatment, metastases, and PC-specific mortality were determined by Cox models adjusted for preoperative characteristics. 



RESULTS: There were 333 (17.7%) men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6 kg/m(2)), all P<0.01. Biopsy GS, pathologic GS, positive surgical margins, lymph node positivity, and extracapsular extension did not differ with AO exposure. At a median follow-up of 85 months, 702 (37.4%) patients had BCR, 603 (32.2%) patients received secondary treatment, 78 (4.1%) had metastases, and 39 (2.1%) died of PC. On multivariable analysis, AO exposure was not associated with BCR, secondary treatment, metastases, or PC mortality. 



CONCLUSIONS: AO exposure was not associated with worse preoperative characteristics such as elevated prostate-specific antigen levels or biopsy GS nor with BCR, secondary treatment, metastases, or PC death. Thus, as data on AO-exposed men mature, possible differences in PC outcomes observed previously are no longer apparent.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1307,

title = {Smoking is a predictor of adverse pathological features at radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital database},

author = {D F Zapata and L E Howard and W J Aronson and C J Kane and M K Terris and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/25872110/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2015-2015&from_sort=pubdate&from_size=100&from_pos=9},

doi = {10.1111/iju.12773 },

isbn = {1442-2042},

year  = {2015},

date = {2015-07-01},

journal = {International journal of urology : official journal of the Japanese Urological Association},

volume = {22},

number = {7},

pages = {658-662},

abstract = {OBJECTIVE: To test the relationship of smoking and aggressive prostate cancer in men undergoing radical prostatectomy. 



METHODS: A retrospective analysis of 2290 men who underwent radical prostatectomy from the Shared Equal Access Regional Cancer Hospital database from 2000 to 2013 was carried out. There were 1592 (70%) non-smokers and 698 (30%) smokers at radical prostatectomy. Logistic regression was used to examine whether smoking predicted Gleason score (≥4 + 3), margin status, extracapsular extension or seminal vesicle invasion. Linear regression was used to test the relationship between smoking and tumor volume. 



RESULTS: Smokers were younger, more likely to be black, had lower body mass index, higher pathological Gleason score, more positive margins and extracapsular extension (all P < 0.05) versus non-smokers. On crude analysis, smoking was associated with positive margins (odds ratio 1.32; P = 0.003) and extracapsular extension (odds ratio 1.26; P = 0.036). After adjusting for multiple clinical factors, smoking remained associated with a 19-35% increased risk of every adverse feature studied, though only the association with extracapsular extension reached significance. On multivariable analysis, a trend for smokers to have larger tumor volumes (geometric mean 5.8 vs 5.3 g; P = 0.062) was found. 



CONCLUSIONS: In patients undergoing radical prostatectomy, there seems to be a trend for smokers to have worse pathological features compared with non-/former smokers. If confirmed in future studies, smoking should be considered a modifiable risk factor for aggressive prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1309,

title = {Is clinical stage T2c prostate cancer an intermediate- or high-risk disease?},

author = {Z Klaassen and A A Singh and L E Howard and Z Feng and B Trock and M K Terris and W J Aronson and M R Cooperberg and C L Amling and C J Kane and A Partin and M Han and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/25492369/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2015-2015&from_sort=pubdate&from_size=100&from_pos=11},

doi = {10.1002/cncr.29147 },

isbn = {1097-0142},

year  = {2015},

date = {2015-05-01},

journal = {Cancer},

volume = {121},

number = {9},

pages = {1414-1421},

abstract = {BACKGROUND: Clinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. According to the D'Amico grouping and American Urological Association guidelines, cT2c is a high risk, whereas the National Comprehensive Cancer Network and the European Urological Association classify cT2c as an intermediate risk. This study assessed whether cT2c tumors without other high-risk factors (clinical stage T2c, not otherwise specified [cT2c-NOS]) behaved as an intermediate or high risk through an analysis of biochemical recurrence (BCR) after radical prostatectomy. 



METHODS: Two thousand seven hundred fifty-nine men from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database and 12,900 men from Johns Hopkins Hospital (JHH) from 1988-2011 and 1982-2012, respectively, were analyzed. Patients were grouped into low-risk (prostate-specific antigen [PSA] 20 ng/mL, Gleason sum = 8-10, or cT3). Men with cT2c tumors who were not otherwise at high risk (ie, PSA< 20 ng/mL and Gleason sum < 8) were placed into a separate category termed cT2c-NOS. Associations between cT2c-NOS and intermediate- and high-risk patients and BCR were tested with the log-rank test and Cox proportional analysis models. 



RESULTS: Ninety-nine men (4%) from SEARCH and 202 men (2%) from JHH had tumors classified as cT2c-NOS. The cT2c-NOS patients had a BCR risk similar to that of the intermediate-risk patients (SEARCH, P = .27; JHH, P = .23) but a significantly lower BCR risk in comparison with the high-risk patients (SEARCH, P < .001; JHH, P < .001). When they were specifically compared with intermediate- and high-risk patients, after adjustments for year and center, cT2c-NOS patients had outcomes comparable to those of intermediate-risk patients (SEARCH, P = .53; JHH, P = .54) but significantly better than those of high-risk patients (SEARCH, P = .003; JHH, P < .001).



CONCLUSIONS: Patients with cT2c disease without other high-risk features had outcomes similar to the outcomes of patients with intermediate-risk PC and significantly better than the outcomes of patients with high-risk PC. These findings suggest that men with cT2c disease should be considered to be at intermediate risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1308,

title = {Prostate-specific antigen level, stage or Gleason score: which is best for predicting outcomes after radical prostatectomy, and does it vary by the outcome being measured? Results from Shared Equal Access Regional Cancer Hospital database},

author = {P Mithal and L E Howard and W J Aronson and C J Kane and M R Cooperberg and M K Terris and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/25728968/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2015-2015&from_sort=pubdate&from_size=100&from_pos=10},

doi = {10.1111/iju.12704 },

isbn = {1442-2042},

year  = {2015},

date = {2015-04-01},

journal = {International journal of urology : official journal of the Japanese Urological Association},

volume = {22},

number = {4},

pages = {362-366},

abstract = {OBJECTIVES: To assess the ability of preoperative prostate-specific antigen level, Gleason score and stage to predict prostate cancer outcomes beyond biochemical recurrence, specifically castration-resistant prostate cancer, metastases and prostate cancer-specific mortality in radical prostatectomy patients. 



METHODS: We carried out a retrospective study of 2735 men in the Shared Equal Access Regional Cancer Hospital database treated by radical prostatectomy from 1988 to 2011 with data available on pathological stage, grade and preoperative prostate-specific antigen. We used Cox hazards analyses to examine the predictive accuracy (c-index) of the preoperative prostate-specific antigen (log-transformed), path Gleason score (≤ 7, 3 + 4, 4 + 3 and 8-10) and path stage grouping (pT2 negative margins; pT2 positive margins; pT3a negative margins; pT3a positive margins; pT3b; vs positive nodes) to predict biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality. 



RESULTS: Median follow up was 8.7 years, during which, 937 (34%) had biochemical recurrence, 108 (4%) castration-resistant prostate cancer, 127 (5%) metastases and 68 (2%) prostate cancer-specific mortality. For the outcomes of biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality, the c-indices were, respectively: prostate-specific antigen 0.65, 0.66, 0.64 and 0.69; Gleason score 0.66, 0.83, 0.76 and 0.85; and pathological stage group 0.69, 0.76, 0.72 and 0.80. 



CONCLUSIONS: Gleason score can predict with very high accuracy prostate cancer-specific mortality in patients undergoing radical prostatectomy. Thus, Gleason score should be given more weight in nomograms to predict prostate cancer-specific mortality. Furthermore, men with a high Gleason score should be given special consideration for adjuvant treatment or referral to clinical trials because of a higher risk of prostate cancer-specific mortality.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e130a,

title = {Practice patterns and predictors of followup imaging after a negative bone scan in men with castration resistant prostate cancer: results from the SEARCH database},

author = {K N Sourbeer and L E Howard and D M Moreira and H S Amarasekara and L D Chow and D C Cockrell and B T Hanyok and C L Pratson and C J Kane and M K Terris and W J Aronson and M R Cooperberg and C L Amling and R K Hernandez and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/25463986/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2015-2015&from_sort=pubdate&from_size=100&from_pos=12},

doi = {10.1016/j.juro.2014.11.014},

isbn = {1527-3792},

year  = {2015},

date = {2015-04-01},

journal = {The Journal of urology},

volume = {193},

number = {4},

pages = {1232-1238},

abstract = {PURPOSE: We investigated imaging practice patterns in men with nonmetastatic (M0) castration resistant prostate cancer. 



MATERIALS AND METHODS: We analyzed data on 247 patients with documented M0 CRPC from the SEARCH database. Patients were selected regardless of primary treatment modality and all had a negative bone scan after a castration resistant prostate cancer diagnosis. Cox models were used to test associations of time to a second imaging test with several demographic and clinical factors. 



RESULTS: During a median followup of 29.0 months (IQR 12.9-43.5) after a post-castration resistant prostate cancer bone scan was negative, 190 patients (77%) underwent a second imaging test. On univariable analysis patients with higher prostate specific antigen (HR 1.13, p = 0.016), shorter prostate specific antigen doubling time (HR 0.79, p < 0.001) and faster prostate specific antigen velocity (HR 1.01, p < 0.001) were more likely to undergo a second imaging test. Treatment center was also a significant predictor of a second imaging test (p = 0.010). No other factor was a significant predictor. Results were similar on multivariable analysis. It was estimated that approximately 20% of men with a prostate specific antigen doubling time of less than 3 months did not undergo an imaging test in the first year after a post-castration resistant prostate cancer negative bone scan. However, 50% of patients with prostate specific antigen doubling time 15 months or greater underwent a second imaging test in the first year.



CONCLUSIONS: Clinicians use some known predictors of positive imaging tests to determine which patients with M0 castration resistant prostate cancer undergo a second imaging test . However, there may be under imaging in those at high risk and over imaging in those at low risk. Further studies are needed to identify risk factors for metastasis and form clear imaging guidelines in patients with M0 castration resistant prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e130b,

title = {Serum lipid profile and risk of prostate cancer recurrence: Results from the SEARCH database},

author = {E H Allott and L E Howard and M R Cooperberg and C J Kane and W J Aronson and M K Terris and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/25304929/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2014-2014&from_sort=pubdate&from_size=100&from_pos=3},

doi = {10.1158/1055-9965.EPI-14-0458 },

isbn = {1538-7755},

year  = {2014},

date = {2014-11-01},

journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},

volume = {23},

number = {11},

pages = {2349-2356},

abstract = {BACKGROUND: Evidence for an association between total cholesterol, low- and high-density lipoproteins (LDL and HDL, respectively), triglycerides, and prostate cancer is conflicting. Given that prostate cancer and dyslipidemia affect large proportions of Western society, understanding these associations has public health importance. 



METHODS: We conducted a retrospective cohort analysis of 843 radical prostatectomy (RP) patients who never used statins before surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analysis was used to investigate the association between cholesterol, LDL, HDL, and triglycerides and biochemical recurrence risk. In secondary analysis, we explored these associations in patients with dyslipidemia, defined using National Cholesterol Education Program guidelines. 



RESULTS: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence [HRper 10 mg/dl, 1.03; 95% confidence interval (CI), 1.01-1.05] but associations between total cholesterol, LDL and HDL, and recurrence risk were null. However, among men with dyslipidemia, each 10 mg/dl increase in cholesterol and HDL was associated with 9% increased recurrence risk (HR, 1.09; 95% CI, 1.01-1.17) and 39% reduced recurrence risk (HR, 0.61; 95% CI, 0.41-0.91), respectively. 



CONCLUSIONS: Elevated serum triglycerides were associated with increased risk of prostate cancer recurrence. Cholesterol, LDL, or HDL were not associated with recurrence risk among all men. However, among men with dyslipidemia, elevated cholesterol and HDL levels were associated with increased and decreased risk of recurrence, respectively. IMPACT: These findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e130c,

title = {Postoperative statin use and risk of biochemical recurrence following radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database},

author = {E H Allott and L E Howard and M R Cooperberg and C J Kane and W J Aronson and M K Terris and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/24588774/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2014-2014&from_sort=pubdate&from_size=100&from_pos=4},

doi = {10.1111/bju.12720 },

isbn = {1464-410X},

year  = {2014},

date = {2014-11-01},

journal = {BJU international},

volume = {114},

number = {5},

pages = {661-666},

abstract = {OBJECTIVE: To investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP. 



PATIENTS AND METHODS: We conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men. 



RESULTS: After adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384). 



CONCLUSION: In this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e130d,

title = {The impact of pathologic staging on the long-term oncologic outcomes of patients with clinically high-risk prostate cancer},

author = {M R Abern and M K Terris and W J Aronson and C J Kane and C L Amling and M R Cooperberg and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/24647966/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2014-2014&from_sort=pubdate&from_size=100&from_pos=5},

doi = {10.1002/cncr.28647 },

isbn = {1097-0142},

year  = {2014},

date = {2014-06-01},

journal = {Cancer},

volume = {120},

number = {11},

pages = {1656-1662},

abstract = {BACKGROUND: In the prostate-specific antigen (PSA) screening era, approximately 15% of US men still present with clinically high-risk prostate cancer (PC). However, high-risk PC may be downgraded/downstaged at radical prostatectomy (RP), making additional therapy unnecessary. The authors tested the oncologic outcomes in men with clinically high-risk disease stratified on RP pathology. 



METHODS: A total of 611 men with high-risk PC (PSA level > 20 ng/mL, biopsy Gleason sum [bGS] ≥ 8, or clinical classification of ≥ T3) underwent RP and pelvic lymphadenectomy between 1998 and 2011. Outcomes included biochemical disease recurrence (BCR), receipt of androgen deprivation therapy (ADT), metastases, and PC-specific and overall survival. RP pathology was classified as unfavorable (pathologic Gleason sum ≥ 8, pathologic classification of ≥ T3, or lymph node-positive disease), or favorable (no unfavorable features). Multivariable analyses tested oncologic outcomes stratified by pathologic classification. 



RESULTS: Overall, 527 men had complete pathologic data and were included in the current analysis. Of the cohort, 206 of 527 men (39%) had favorable pathology. This finding was more common in men with only 1 clinical high-risk feature, and a lower body mass index, PSA level, bGS, and percentage positive biopsy cores. Favorable pathology was associated with decreased BCR (hazards ratio [HR], 0.34), metastases (HR, 0.17), and PC death (HR, 0.17). After a median follow-up of 82 months (range, 49 months-131 months), 193 of the 527 men (37%) received ADT, including only 35 of the 206 men with favorable pathology (17%). Unfavorable pathology was associated with early (≤ 5 years) but not late treatment with ADT. 



CONCLUSIONS: In a large cohort of men with high-risk PC who were managed with RP, 39% had favorable pathology and superior oncologic outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1311,

title = {Multi-institutional validation of the CAPRA-S score to predict disease recurrence and mortality after radical prostatectomy},

author = {S Punnen and S J Freedland and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and P R Carroll and M R Cooperberg},

url = {https://pubmed.ncbi.nlm.nih.gov/23587869/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2014-2014&from_sort=pubdate&from_size=100&from_pos=8},

doi = {10.1016/j.eururo.2013.03.058},

isbn = {1873-7560},

year  = {2014},

date = {2014-06-01},

journal = {European urology},

volume = {65},

number = {6},

pages = {1171-1177},

abstract = {BACKGROUND: The University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally. 



OBJECTIVE: To validate CAPRA-S in a large, multi-institutional, external database. 



DESIGN, SETTING, AND PARTICIPANTS: The Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670 men (92%) had complete data to calculate a CAPRA-S score. 



INTERVENTION: RP.



 OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index.



RESULTS AND LIMITATIONS: The mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0-2, 3-5, and 6-10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The c-index for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events. 



CONCLUSIONS: In this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index >0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1313,

title = {Detectable prostate-specific antigen Nadir during androgen-deprivation therapy predicts adverse prostate cancer-specific outcomes: results from the SEARCH database},

author = {C J Keto and W J Aronson and M K Terris and J C Presti and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/23245686/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2014-2014&from_sort=pubdate&from_size=100&from_pos=9},

doi = {10.1016/j.eururo.2012.11.052},

isbn = {1873-7560},

year  = {2014},

date = {2014-03-01},

journal = {European urology},

volume = {65},

number = {3},

pages = {620-627},

abstract = {BACKGROUND: A prostate-specific antigen (PSA) level <0.2 ng/ml 8 mo after starting on androgen-deprivation therapy (ADT) is correlated with better outcomes. However, not all men reach a nadir PSA level within 8 mo. Whether the lowest PSA on ADT-specifically, <0.2 ng/ml-can be used for risk stratification is untested. 



OBJECTIVE: We examined the predictive value of small but detectable PSA nadir values on prostate cancer (PCa)-specific outcomes in men treated with early ADT after radical prostatectomy (RP). 



DESIGN, SETTING, AND PARTICIPANTS: We performed a retrospective review of men treated with ADT after RP before metastases from the SEARCH database. We identified 402 men treated with ADT for elevated PSA following RP, of whom 294 men had complete data. Median follow-up after PSA nadir was 49 mo. All men had a PSA nadir <4 ng/ml; 223 men (76%) had an undetectable nadir. 



INTERVENTION: ADT for an elevated PSA following RP with no radiographic evidence of metastatic disease. 



OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: PSA nadir on ADT was defined as the lowest PSA value during ADT. Proportional hazards models and the C index were used to test the association and predictive accuracy, respectively, between PSA nadir and PCa-specific outcomes. 



RESULTS AND LIMITATIONS: Men with a PSA nadir between 0.01 and 0.2 ng/ml had a greater risk of progression to castration-resistant PCa (CRPC) (hazard ratio [HR]: 5.14; p<0.001), metastases (HR: 3.98; p=0.006), and PCa-specific mortality (PCSM) (HR: 5.33; p=0.003) than men with an undetectable nadir. When data were restricted to men followed with ultrasensitive PSA values (sensitivity of 0.01 ng/ml), the C index of PSA nadir alone for predicting CRPC, metastases, and PCSM was 0.88, 0.91, and 0.96, respectively. 



CONCLUSIONS: A PSA nadir on ADT, even at a very low level, strongly predicts progression to CRPC, metastases, and PCSM. Men with a detectable PSA nadir during ADT should be considered for clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ed02787e4b0a61c4cc92a42,

title = {Predicting bone scan positivity after biochemical recurrence following radical prostatectomy in both hormone-naive men and patients receiving androgen-deprivation therapy: results from the SEARCH database},

author = {D M Moreira and M R Cooperberg and L E Howard and W J Aronson and C J Kane and M K Terris and C L Amling and M Kuchibhatla and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/24418913/},

doi = {10.1038/pcan.2013.59 },

isbn = {1476-5608},

year  = {2014},

date = {2014-03-01},

journal = {Prostate cancer and prostatic diseases},

volume = {17},

number = {1},

pages = {91-96},

abstract = {BACKGROUND: To evaluate the factors associated with positive bone scans after biochemical recurrence (BCR) following radical prostatectomy in both hormone-naive subjects and subjects after androgen-deprivation therapy (ADT). 



METHODS: Retrospective analysis of 380 bone scans of 301 hormone-naive subjects and 214 bone scans of 137 subjects after ADT following BCR from the Shared Equal Access Regional Cancer Hospital database. Generalized estimating equations and local regression plots were used to evaluate bone scan positivity by patients' demographics, pathological features, PSA levels and kinetics. 



RESULTS: Among hormone-naive subjects and subjects on ADT, bone scan positivity was seen in 24 (6%) and 65 (30%) subjects, respectively. In hormone-naive subjects, the higher prescan PSA, higher PSA velocity (PSAV) and shorter PSA doubling time (PSADT) were significantly associated with positive scans (P=0.008, P<0.001 and P<0.001, respectively). In subjects after ADT, the prescan PSA, PSAV and PSADT were significantly associated with positive scans (P=0.011, P<0.001 and P=0.002, respectively). Regression plots showed increased scan positivity with increasing PSA levels and shortening PSADT (all P<0.001) for both hormone-naive subjects and subjects after ADT. For a given PSA level and PSADT, subjects on ADT had higher bone scan positivity. 



CONCLUSIONS: In both hormone-naive subjects and subjects after ADT, more aggressive and advanced disease identified by higher PSA levels, higher PSAV and shorter PSADT were associated with higher bone scan positivity. For the same PSA level and PSADT, subjects after ADT had higher bone scan positivity than hormone-naive subjects. Therefore, PSA levels and kinetics may be used as selection criteria for bone scan in these patients.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e130e,

title = {Cigarette smoking is associated with an increased risk of biochemical disease recurrence, metastasis, castration-resistant prostate cancer, and mortality after radical prostatectomy: results from the SEARCH database},

author = {D M Moreira and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and P Boffetta and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/24127391/?from_term=%28Freedland%5BAuthor%5D%29+AND+%28Kane%5BAuthor%5D%29&from_filter=years.2014-2014&from_sort=pubdate&from_size=100&from_pos=7},

doi = {10.1002/cncr.28423 },

isbn = {1097-0142},

year  = {2014},

date = {2014-01-01},

journal = {Cancer},

volume = {120},

number = {2},

pages = {197-204},

abstract = {BACKGROUND: The current study was conducted to analyze the association between cigarette smoking and metastasis (the primary outcome) as well as time to biochemical disease recurrence (BCR), metastasis, castration-resistant prostate cancer (CRPC), and prostate cancer-specific and overall mortality (secondary outcomes) after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital cohort. 



METHODS: A retrospective analysis was performed of 1450 subjects for whom smoking status was available from preoperative notes. Analysis of baseline characteristics by smoking status was performed using the chi-square and rank sum tests. The association between smoking status and time to the event was analyzed using Kaplan-Meier plots, the log-rank test, and Cox and competing risk models. 



RESULTS: A total of 549 men (33%) men were active smokers and 1121 (67%) were nonsmokers at the time of surgery. Current smokers were younger and had a lower body mass index, higher prostate-specific antigen level, and more extracapsular extension and seminal vesicle invasion (all P<.05). A total of 509 patients, 26 patients, 30 patients, 18 patients, and 217 patients, respectively, experienced BCR, metastasis, CRPC, prostate cancer-related death, and any-cause death over a median follow-up of 62 months, 75 months, 61 months, 78 months, and 78 months, respectively. After adjusting for preoperative features, active smoking was found to be associated with an increased risk of BCR (hazards ratio [HR], 1.25; P=.024), metastasis (HR, 2.64; P=.026), CRPC (HR, 2.62; P=.021), and overall mortality (HR, 2.14; P<.001). Similar results were noted after further adjustment for postoperative features, with the exception of BCR (HR, 1.10; P=.335), metastasis (HR, 2.51; P=.044), CRPC (HR, 2.67; P=.015), and death (HR, 2.03; P<.001). 



CONCLUSIONS: Among patients undergoing radical prostatectomy, cigarette smoking was associated with an increased risk of metastasis. In addition, smoking was associated with a higher risk of BCR, CRPC, and overall mortality. If confirmed, these data suggest that smoking is a modifiable risk factor in patients with aggressive prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid24100644,

title = {Metformin does not affect risk of biochemical recurrence following radical prostatectomy: results from the SEARCĦ database},

author = {E H Allott and M R Abern and L Gerber and C J Keto and W J Aronson and M K Terris and C J Kane and C L Amling and M R Cooperberg and P G Moorman and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/24100644/},

doi = {10.1038/pcan.2013.48},

year  = {2013},

date = {2013-12-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {16},

number = {4},

pages = {391--397},

abstract = {Background: While epidemiologic studies suggest that metformin use among diabetics may decrease prostate cancer (PC) incidence, the effect of metformin use on PC outcome is unclear. We investigated the association between pre-operative metformin use, dose and duration of use and biochemical recurrence (BCR) in PC patients with diabetes who underwent radical prostatectomy (RP).



Methods: We conducted a retrospective cohort analysis within the Shared Equal Access Regional Cancer Hospital (SEARCH) database of 371 PC patients with diabetes who underwent RP. Time to BCR between metformin users and non-users, and by metformin dose and duration of use was assessed using multivariable Cox proportional analysis adjusted for demographic, clinical and/or pathologic features. Time to castrate-resistant PC (CRPC), metastases and PC-specific mortality were explored as secondary outcomes using unadjusted analyses.



Results: Of 371 diabetic men, 156 (42%) were using metformin before RP. Metformin use was associated with more recent year of surgery (P<0.0001) but no clinical or pathologic characteristics. After adjustment for year of surgery, clinical and pathologic features, there were no associations between metformin use (hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.61-1.41), high metformin dose (HR 0.96; 95% CI 0.57-1.61) or duration of use (HR 1.00; 95% CI 0.99-1.02) and time to BCR. A total of 14 patients (3.8%) developed CRPC, 10 (2.7%) distant metastases and 8 (2.2%) died from PC. Unadjusted analysis suggested that high metformin dose vs non-use was associated with increased risk of CRPC (HR 5.1; 95% CI 1.6-16.5), metastases (HR 4.8; 95% CI 1.2-18.5) and PC-specific mortality (HR 5.0; 95% CI 1.1-22.5).



Conclusions: Metformin use, dose or duration of use was not associated with BCR in this cohort of diabetic PC patients treated with RP. The suggestion that higher metformin dose was associated with increased risk of CRPC, metastases and PC-specific mortality merits testing in large prospective studies with longer follow-up.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e130f,

title = {Do nomograms designed to predict biochemical recurrence (BCR) do a better job of predicting more clinically relevant prostate cancer outcomes than BCR? A report from the SEARCH database group},

author = {A E Teeter and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/23806388/?from_term=freedland+kane&from_filter=years.2013-2013&from_sort=pubdate&from_size=100&from_pos=3},

doi = {10.1016/j.urology.2012.10.090},

isbn = {1527-9995},

year  = {2013},

date = {2013-07-01},

journal = {Urology},

volume = {82},

number = {1},

pages = {53-58},

abstract = {Objective: To examine the ability of various postoperative nomograms to predict prostate cancer-specific mortality (PCSM) and to validate that they could predict aggressive biochemical recurrence (BCR). Prostate-specific antigen (PSA), grade, and stage are the classic triad used to predict BCR after radical prostatectomy (RP). Multiple nomograms use these to predict risk of BCR. A previous study showed that several nomograms could predict aggressive BCR (prostate-specific antigen doubling time [PSADT] <9 months) more accurately than BCR. However, it remains unknown if they can predict more definitive endpoints, such as PCSM.



Methods: We performed Cox analyses to examine the ability of 4 postoperative nomograms, the Duke Prostate Center (DPC) nomogram, the Kattan postoperative nomogram, the Johns Hopkins Hospital (JHH) nomogram, and the joint Center for Prostate Disease Research(CPDR)/Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) nomogram to predict BCR and PCSM among 1778 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database who underwent RP between 1990 and 2009. We also compared their ability to predict BCR and aggressive BCR in a subset of men. We calculated the c-index for each nomogram to determine its predictive accuracy for estimating actual outcomes.



Results: We found that each nomogram could predict aggressive BCR and PCSM in a statistically significant manner and that they all predicted PCSM more accurately than they predicted BCR (ie, with higher c-index values).



Conclusion: Currently available nomograms used to predict BCR accurately predict PCSM and other more clinically relevant endpoints. Moreover, not only do they significantly predict PCSM, but do so with generally greater accuracy than BCR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1312,

title = {Diabetes predicts metastasis after radical prostatectomy in obese men: results from the SEARCH database},

author = {C Wu and W J Aronson and M K Terris and Presti J C Jr and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/23305170/?from_term=freedland+kane&from_filter=years.2013-2013&from_sort=pubdate&from_size=100&from_pos=6},

doi = {10.1111/j.1464-410X.2012.11687.x },

isbn = {1464-410X},

year  = {2013},

date = {2013-06-01},

journal = {BJU international},

volume = {111},

number = {8},

pages = {310},

abstract = {Objective: To examine the association between diabetes and metastasis risk after radical prostatectomy (RP) and to determine if race or obesity modifies this relationship.



Patients and methods: Patients comprised 2058 US veterans with prostate cancer (PCa) enrolled in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database and treated with RP between 1988 and 2010. The association of diabetes with metastasis risk or secondary treatment rates was examined using Cox proportional hazards, adjusting for preoperative and, separately, clinical and postoperative findings. The effect modification by race (black vs white) and obesity (body mass index [BMI] ≥30 vs <30 kg/m(2) ) was tested via interaction terms.



Results: Men with diabetes had higher BMIs and were more likely to be non-white (all P ≤ 0.001). On multivariable analysis, diabetes was not associated with metastasis risk (P ≥ 0.45), but, among men with diabetes, longer diabetes duration was associated with higher metastasis risk (P ≤ 0.035). When stratified by obesity, diabetes was linked with higher metastasis risk in obese but not in non-obese men (P-interaction ≤ 0.037), but there was no significant interaction with race (P-interaction ≥ 0.56). Diabetes also predicted more aggressive secondary treatment among obese men but less aggressive treatment among non-obese men (hazard ratio 1.39 vs 0.63, P-interaction = 0.006). Where applicable, results were similar for both pre- and postoperative models.



Conclusions: Diabetes was not associated with metastasis risk overall. Stratification by obesity yielded significant differences, with diabetes linked to a fourfold higher metastasis risk in obese men, despite predicting more aggressive secondary treatment. Longer diabetes duration was also associated with increased metastasis risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1314,

title = {Delayed radical prostatectomy for intermediate-risk prostate cancer is associated with biochemical recurrence: possible implications for active surveillance from the SEARCH database},

author = {M R Abern and W J Aronson and M K Terris and C J Kane and Presti J C Jr and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/22996686/?from_term=freedland+kane&from_filter=years.2013-2013&from_sort=pubdate&from_size=100&from_pos=7},

doi = {10.1002/pros.22582 },

isbn = {1097-0045},

year  = {2013},

date = {2013-03-01},

journal = {The Prostate},

volume = {73},

number = {4},

pages = {409-417},

abstract = {Introduction: Active surveillance (AS) is increasingly accepted as appropriate management for low-risk prostate cancer (PC) patients. It is unknown whether delaying radical prostatectomy (RP) is associated with increased risk of biochemical recurrence (BCR) for men with intermediate-risk PC.



Methods: We performed a retrospective analysis of 1,561 low and intermediate-risk men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database treated with RP between 1988 and 2011. Patients were stratified by interval between diagnosis and RP (≤ 3, 3-6, 6-9, or >9 months) and by risk using the D'Amico classification. Cox proportional hazard models were used to analyze BCR. Logistic regression was used to analyze positive surgical margins (PSM), extracapsular extension (ECE), and pathologic upgrading.



Results: Overall, 813 (52%) men were low-risk, and 748 (48%) intermediate-risk. Median follow-up among men without recurrence was 52.9 months, during which 437 men (38.9%) recurred. For low-risk men, RP delays were unrelated to BCR, ECE, PSM, or upgrading (all P > 0.05). For intermediate-risk men, however, delays >9 months were significantly related to BCR (HR: 2.10, P = 0.01) and PSM (OR: 4.08, P < 0.01). Delays >9 months were associated with BCR in subsets of intermediate-risk men with biopsy Gleason score ≤ 3 + 4 (HR: 2.51, P < 0.01), PSA ≤ 6 (HR: 2.82, P = 0.06), and low tumor volume (HR: 2.59, P = 0.06).



Conclusions: For low-risk men, delayed RP did not significantly affect outcome. For men with intermediate-risk disease, delays >9 months predicted greater BCR and PSM risk. If confirmed in future studies, this suggests delayed RP for intermediate-risk PC may compromise outcomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1310,

title = {High serum folate is associated with reduced biochemical recurrence after radical prostatectomy: results from the SEARCH Database},

author = {D M Moreira and L L Bañez and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/23849564/?from_term=freedland+kane&from_filter=years.2013-2013&from_sort=pubdate&from_size=100&from_pos=4},

doi = {10.1590/S1677-5538.IBJU.2013.03.03 },

isbn = {1677-6119},

year  = {2013},

date = {2013-01-01},

journal = {International braz j urol : official journal of the Brazilian Society of Urology},

volume = {39},

number = {3},

pages = {312-8; discussion 319},

abstract = {Introduction: To analyze the association between serum levels of folate and risk of biochemical recurrence after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.



Materials and methods: Retrospective analysis of 135 subjects from the SEARCH database treated between 1991-2009 with available preoperative serum folate levels. Patients' characteristics at the time of the surgery were analyzed with ranksum and linear regression. Uni- and multivariable analyses of folate levels (log-transformed) and time to biochemical recurrence were performed with Cox proportional hazards.



Results: The median preoperative folate level was 11.6 ng/mL (reference = 1.5-20.0 ng/mL). Folate levels were significantly lower among African-American men than Caucasians (P = 0.003). In univariable analysis, higher folate levels were associated with more recent year of surgery (P < 0.001) and lower preoperative PSA (P = 0.003). In univariable analysis, there was a trend towards lower risk of biochemical recurrence among men with high folate levels (HR = 0.61, 95 %CI = 0.37-1.03, P = 0.064). After adjustments for patients characteristics' and pre- and post-operative clinical and pathological findings, higher serum levels of folate were independently associated with lower risk for biochemical recurrence (HR = 0.42, 95 %CI = 0.20-0.89, P = 0.023).



Conclusion: In a cohort of men undergoing radical prostatectomy at several VAs across the country, higher serum folate levels were associated with lower PSA and lower risk for biochemical failure. While the source of the folate in the serum in this study is unknown (i.e. diet vs. supplement), these findings, if confirmed, suggest a potential role of folic acid supplementation or increased consumption of folate rich foods to reduce the risk of recurrence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1315,

title = {Obesity, prostate-specific antigen nadir, and biochemical recurrence after radical prostatectomy: biology or technique? Results from the SEARCH database},

author = {T Ho and L Gerber and W J Aronson and M K Terris and J C Presti and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/22921964/?from_term=freedland+kane&from_filter=years.2012-2012&from_sort=pubdate&from_size=100&from_pos=3},

doi = {10.1016/j.eururo.2012.08.015},

isbn = {1873-7560},

year  = {2012},

date = {2012-11-01},

journal = {European urology},

volume = {62},

number = {5},

pages = {910-916},

abstract = {Background: Obesity is associated with an increased risk of biochemical recurrence (BCR) after radical prostatectomy (RP). It is unclear whether this is due to technical challenges related to operating on obese men or other biologic factors.



Objective: To examine whether obesity predicts higher prostate-specific antigen (PSA) nadir (as a measure of residual PSA-producing tissue) after RP and if this accounts for the greater BCR risk in obese men.



Design, setting, and participants: A retrospective analysis of 1038 RP patients from 2001 to 2010 in the multicenter US Veterans Administration-based Shared Equal Access Regional Cancer Hospital database with median follow-up of 41 mo.



Intervention: All patients underwent RP.



Outcome measurements and statistical analysis: We evaluated the relationship between body mass index (BMI) and ultrasensitive PSA nadir within 6 mo after RP. Adjusted proportional hazards models were used to examine the association between BMI and BCR with and without PSA nadir.



Results and limitations: Mean BMI was 28.5 kg/m2. Higher BMI was associated with higher PSA nadir on both univariable (p=0.001) and multivariable analyses (p<0.001). Increased BMI was associated with increased BCR risk (hazard ratio [HR]: 1.06; p=0.007). Adjusting for PSA nadir slightly attenuated, but did not eliminate, this association (HR: 1.04, p=0.043). When stratified by PSA nadir, obesity only significantly predicted BCR in men with an undetectable nadir (p=0.006). Unfortunately, other clinically relevant end points such as metastasis or mortality were not available.



Conclusions: Obese men are more likely to have a higher PSA nadir, suggesting that either more advanced disease or technical issues confound an ideal operation. However, even after adjusting for the increased PSA nadir, obesity remained predictive of BCR, suggesting that tumors in obese men are growing faster. This provides further support for the idea that obesity is biologically associated with prostate cancer progression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1318,

title = {Effect of race and socioeconomic status on surgical margins and biochemical outcomes in an equal-access health care setting: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database},

author = {D I Chu and D M Moreira and L Gerber and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/22415377/?from_term=freedland+kane&from_filter=years.2012-2012&from_sort=pubdate&from_size=100&from_pos=6},

doi = {10.1002/cncr.27456 },

isbn = {1097-0142},

year  = {2012},

date = {2012-10-01},

journal = {Cancer},

volume = {118},

number = {20},

pages = {4999-5007},

abstract = {Background: The impact of race and socioeconomic status (SES) in prostate cancer (CaP) outcomes has been well-studied, but controversy remains. The associations of race/SES with intermediate CaP outcomes, including positive surgical margin (PSM) and biochemical recurrence (BCR), were explored in an equal-access setting.



Methods: Data were retrospectively collected from 2502 men in the Shared Equal Access Regional Cancer Hospitals (SEARCH) database who underwent radical prostatectomy from 1989 to 2010. SES (income, education, employment, and poverty) was estimated from linkage of home ZIP code to census data. Logistic regression with adjustment for pre- and postoperative covariates estimated risk for associations between race/SES and pathologic outcomes. Cox proportional hazards models estimated risk for associations between race/SES and time to BCR.



Results: Black men were more likely to have lower SES than white men (P < .001). On multivariate analysis, race was not associated with PSM, but higher SES was associated with less PSM and fewer Gleason sum ≥ 7 pathologic tumors when SES was assessed by education, employment, or poverty (P trend ≤ .051) and income, employment, or poverty (P trend ≤ 0.059), respectively. Crude Cox models showed black men had higher BCR risk (hazards ratio = 1.20, 95% confidence interval = 1.05-1.38, P = .009) that persisted after adjustment for covariates including SES (hazards ratio ≥ 1.18, P ≤ .040). Higher SES measured by income and poverty were associated with less BCR, but only for black men (P trend ≤ .048).



Conclusions: Even in an equal-access setting, higher SES predicted lower PSM risk, and race persisted in predicting BCR despite adjustment for SES. Low SES black patients may be at greatest risk for postprostatectomy BCR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1319,

title = {Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database},

author = {C J Keto and W J Aronson and M K Terris and J C Presti and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/22094083/?from_term=freedland+kane&from_filter=years.2012-2012&from_sort=pubdate&from_size=100&from_pos=7},

doi = {10.1111/j.1464-410X.2011.10754.x },

isbn = {1464-410X},

year  = {2012},

date = {2012-08-01},

journal = {BJU international},

volume = {110},

number = {4},

pages = {492-498},

abstract = {Study Type - Prognosis (cohort series). Level of Evidence 2a. What's known on the subject? and What does the study add? The incidence and prevalence of obesity in the USA and Europe is increasing. Higher body mass index is associated with a lower risk of overall prostate cancer diagnosis but also with an increased risk of high grade prostate cancer. Obese men undergoing primary therapy with radical prostatectomy or external beam radiation are more likely to experience a biochemical recurrence after treatment compared with normal weight men. Finally, obesity is associated with increased prostate-cancer-specific mortality. We hypothesized that obese men on androgen deprivation therapy may be at increased risk for prostate cancer progression. Previous studies have shown that obese men have lower levels of testosterone compared with normal weight men. Additionally, one previous study found that obese men have higher levels of testosterone on androgen deprivation therapy. Men with higher levels of testosterone on androgen deprivation therapy are at increased risk of prostate cancer progression. We found that men with higher body mass index were at increased risk of progression to castration-resistant prostate cancer, development of metastases and prostate-cancer-specific mortality. When we adjusted for various clinicopathological characteristics, obese men were at increased risk of progression to castration-resistant prostate cancer and development of metastases. The results of our study help generate hypotheses for further study regarding the mechanisms between obesity and aggressive prostate cancer.



Objective: • To investigate whether obesity predicts poor outcomes in men starting androgen deprivation therapy (ADT) before metastasis, since previous studies found worse outcomes after surgery and radiation for obese men.



Methods: • A retrospective review was carried out of 287 men in the SEARCH database treated with radical prostatectomy between 1988 and 2009. • Body mass index (BMI) was categorized to <25, 25-29.9 and ≥ 30 kg/m2. • Proportional hazards models were used to test the association between BMI and time to castration-resistant prostate cancer (PC), metastases and PC-specific mortality adjusting for demographic and clinicopathological data.



Results: • During a median 73-month follow-up after radical prostatectomy, 403 men (14%) received early ADT. • Among 287 men with complete data, median BMI was 28.3 kg/m2. • Median follow-up from the start of ADT was 52 months during which 44 men developed castration-resistant PC, 34 developed metastases and 24 died from PC. • In multivariate analysis, higher BMI was associated with a trend for greater risk of progression to castration-resistant PC (P= 0.063), a more than threefold increased risk of developing metastases (P= 0.027) and a trend toward worse PC-specific mortality (P= 0.119). • Prognostic biomarkers did not differ between BMI groups.



Conclusions: • Among men treated with early ADT, our results suggest that obese men may have increased risk of PC progression. • These data support the general hypothesis that obesity is associated with aggressive PC, although validation of these findings and further study of the mechanisms linking obesity and poor PC outcomes are required.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1316,

title = {Are repeat prostate biopsies safe? A cohort analysis from the SEARCH database},

author = {R P Kopp and S P Stroup and F R Schroeck and S J Freedland and F Millard and M K Terris and W J Aronson and Presti J C Jr and C L Amling and C J Kane},

url = {https://pubmed.ncbi.nlm.nih.gov/22498218/?from_term=freedland+kane&from_filter=years.2012-2012&from_sort=pubdate&from_size=100&from_pos=4},

doi = {10.1016/j.juro.2012.01.083 },

isbn = {1527-3792},

year  = {2012},

date = {2012-06-01},

journal = {The Journal of urology},

volume = {187},

number = {6},

pages = {2056-2060},

abstract = {Purpose: Patients question whether multiple biopsy sessions cause worse prostate cancer outcomes. Therefore, we investigated whether there is an association between the number of prior biopsy sessions and biochemical recurrence after radical prostatectomy.



Materials and methods: Men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database who underwent radical prostatectomy between 1988 and 2010 after a known number of prior biopsies were included in the analysis. Number of biopsy sessions (range 1 to 8) was examined as a continuous and categorical (1, 2 and 3 to 8) variable. Biochemical recurrence was defined as a prostate specific antigen greater than 0.2 ng/ml, 2 values at 0.2 ng/ml or secondary treatment for an increased prostate specific antigen. The association between number of prior biopsy sessions and biochemical recurrence was analyzed using the Cox proportional hazards model. Kaplan-Meier estimates of freedom from biochemical recurrence were compared among the groups.



Results: Of the 2,739 men in the SEARCH database who met the inclusion criteria 2,251 (82%) had only 1 biopsy, 365(13%) had 2 biopsies and 123 (5%) had 3 or more biopsies. More biopsy sessions were associated with higher prostate specific antigen (p<0.001), greater prostate weight (p<0.001), lower biopsy Gleason sum (p=0.01) and more organ confined (pT2) disease (p=0.017). The Cox proportional hazards model demonstrated no association between number of biopsy sessions as a continuous or categorical variable and biochemical recurrence. Kaplan-Meier estimates of freedom from biochemical recurrence were similar across biopsy groups (log rank p=0.211).



Conclusions: Multiple biopsy sessions are not associated with an increased risk of biochemical recurrence in men undergoing radical prostatectomy. Multiple biopsy sessions appear to select for a low risk cohort.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e1317,

title = {Does salvage radiation therapy change the biology of recurrent prostate cancer based on PSA doubling times? Results from the SEARCH database},

author = {R L Muller and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/22446345/?from_term=freedland+kane&from_filter=years.2012-2012&from_sort=pubdate&from_size=100&from_pos=5},

doi = {10.1016/j.urology.2012.01.034 },

isbn = {1527-9995},

year  = {2012},

date = {2012-05-01},

journal = {Urology},

volume = {79},

number = {5},

pages = {1105-1110},

abstract = {Objective: To investigate whether salvage radiation therapy (SRT) may promote prostate cancer (PCa) transformation to more aggressive phenotypes. To accomplish that, we identified men who underwent SRT after radical prostatectomy for PCa and failed SRT. PSA doubling time (PSADT) was used as a surrogate endpoint for cancer aggressiveness. We compared PSADT calculated before start of SRT and after SRT failure.



Methods: Of 287 men in the SEARCH database since 1988 who underwent SRT, we detected 78 with SRT failure defined as PSA ≥ 0.2 ng/mL above the post-SRT nadir. Of these, 39 had PSADT available before and after SRT, which was compared using Wilcoxon's paired test with men serving as their own controls. We tested predictors of PSADT change using multivariable logistic regression.



Results: There were no differences in PSADT before and after SRT (10.2 vs 12.6 months; P = .46). However, in some individual cases, large changes were observed. Only seminal vesicle invasion showed a trend towards an association with a shorter post-SRT PSADT relative to the pre-SRT PSADT (P = .13).



Conclusion: Overall, the PSADT after and before SRT were statistically identical, suggesting that after SRT failure, PCa does not emerge with more aggressive biological features. Further studies are needed to identify predictors and the clinical relevance of individual PSADT changes noted in our study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid21894174,

title = {Preoperative weight change and risk of adverse outcome following radical prostatectomy: results from the Shared Equal Access Regional Cancer Ħospital database},

author = {B M Whitley and D M Moreira and J A Thomas and W J Aronson and M K Terris and J C Presti and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/21894174/?from_sort=pubdate&from_size=100&from_term=SEARCH+Database+Study+Group%5BCorporate+Author%5D&from_pos=3},

doi = {10.1038/pcan.2011.42},

year  = {2011},

date = {2011-12-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {14},

number = {4},

pages = {361--366},

abstract = {BACKGROUND: We examined the relationship between weight change in the year before radical prostatectomy (RP) and biochemical recurrence (BCR) and adverse pathology.



METHODS: We abstracted data from 359 men undergoing RP in the SEARCH (Shared Equal Access Regional Cancer Hospital) database between 2001-2007. Logistic regression and Cox proportional hazards models were used to test the association between weight change in the year before surgery and adverse pathology and BCR, respectively.



RESULTS: In all, 152 (42%) men gained weight, 193 (54%) lost weight and 14 (4%) had the same weight. Among weight gainers, median gain was 2.4 kg and among weight losers, median loss was 2.7 kg. As a continuous variable, weight change was not associated with adverse pathology or BCR (all P>0.05). In secondary analysis, on multivariate analysis, men gaining ≥ 2.5 kg were at higher BCR risk (hazards ratio=1.65, 95% confidence interval (CI): 1.03-2.64, P=0.04) while weight loss ≥ 2.5 kg was not associated with BCR (hazards ratio=0.83, 95% CI: 0.54-1.29, P=0.41).



CONCLUSIONS: As a continuous variable, weight change was not associated with outcome. In secondary hypothesis-generating analyses, weight gain ≥ 2.5 kg in the year before surgery, regardless of final body mass index, was associated with increased BCR following RP. If validated, these data suggest weight gain ≥ 2.5 kg may promote prostate cancer progression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e131d,

title = {A natural history of weight change in men with prostate cancer on androgen-deprivation therapy (ADT): results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database},

author = {H S Kim and D M Moreira and M R Smith and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/20860651/?from_term=freedland+kane&from_filter=years.2011-2011&from_sort=pubdate&from_size=100&from_pos=4},

doi = {10.1111/j.1464-410X.2010.09679.x },

isbn = {1464-410X},

year  = {2011},

date = {2011-03-01},

journal = {BJU international},

volume = {107},

number = {6},

pages = {924-928},

abstract = {Objectives: • To better understand the natural history of weight change with androgen-deprivation therapy (ADT), we investigated the effect of ADT on body weight among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. • Men undergoing ADT lose lean muscle but gain fat mass, contributing to an overall gain in weight.



Patients and methods: • We identified 132 men in SEARCH who received ADT after radical prostatectomy. • 'Weight change' was defined as the difference in weight before starting ADT (6 months before ADT) and the on-ADT weight (between 6 and 18 months after starting ADT). • In a subanalysis, baseline characteristics of weight-gainers and -losers were analysed using univariate and multivariate analysis to test association with weight change.



Results: • In all, 92 men (70%) gained weight, and 40 (30%) either lost or maintained a stable weight. • On average, weight on ADT was 2.2 kg higher than the weight before ADT, with the mean change for weight-gainers and -losers being +4.2 kg and -2.4 kg, respectively. • This compared with no significant weight change in the year before starting ADT (paired t-test, change -0.7 kg, P= 0.19) or in the second year on ADT (paired t-test, change -0.5 kg, P= 0.46) for 84 men in whom these additional weight values were recorded. • There was no significant association between any of the features examined and weight change on univariate and multivariate analysis.



Conclusion: • In this longitudinal study, ADT was accompanied by significant weight gain (+2.2 kg). This change occurred primarily in the first year of therapy, with men neither losing nor gaining additional weight thereafter.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea399e4b07076c88e131a,

title = {Does PSADT after radical prostatectomy correlate with overall survival?--a report from the SEARCH database group},

author = {A E Teeter and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/21145094/?from_term=freedland+kane&from_filter=years.2011-2011&from_sort=pubdate&from_size=100&from_pos=3},

doi = {10.1016/j.urology.2010.04.071 },

isbn = {1527-9995},

year  = {2011},

date = {2011-01-01},

journal = {Urology},

volume = {77},

number = {1},

pages = {149-153},

abstract = {Objectives: To examine the correlation between the prostate-specific antigen doubling time (PSADT) and overall survival (OS) and among men in the SEARCH database (an older, racially diverse cohort undergoing RP at multiple Veterans Affairs medical centers). Previous studies largely performed at tertiary care centers with relatively young, racially homogenous cohorts found a short PSADT on recurrence after RP portended a poor prognosis.



Methods: We performed a Cox proportional hazards analysis to examine the correlation between postrecurrence PSADT and the interval from recurrence to OS and prostate cancer-specific mortality among 345 men in the SEARCH database who had undergone RP from 1988 to 2008. We examined the PSADT as a categorical variable using the clinically significant cutpoints of <3, 3-8.9, 9-14.9, and ≥15 months.



Results: A PSADT of <3 months (hazard ratio 5.48, P = .002) was associated with poorer OS than a PSADT of ≥15 months. A trend was seen toward worse OS for the men with a PSADT of 3-8.9 months (hazard ratio 1.70, P = .07). PSADTs of <3 months (P < .001) and 3-8.9 months (P = .004) were associated with an increased risk of prostate cancer-specific mortality.



Conclusions: In an older, racially diverse cohort, recurrence with a PSADT of <9 months was associated with worse all-cause mortality. The results of the present study have validated previous findings that PSADT is a useful tool for identifying men at increased risk of all-cause mortality early in their disease course.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e131c,

title = {Postoperative prostate-specific antigen nadir improves accuracy for predicting biochemical recurrence after radical prostatectomy: Results from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center databases},

author = {D M Moreira and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and L L Sun and J W Moul and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/20880361/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=3},

doi = {10.1111/j.1442-2042.2010.02631.x },

isbn = {1442-2042},

year  = {2010},

date = {2010-11-01},

journal = {International journal of urology : official journal of the Japanese Urological Association},

volume = {17},

number = {11},

pages = {914-922},

abstract = {Objectives: We previously showed that prostate-specific antigen (PSA) nadir after radical prostatectomy (RP) significantly predicts biochemical recurrence (BCR). Herein, we sought to explore the effect of including PSA nadir into commonly used models on their accuracy to predict BCR after RP.



Methods: This was a retrospective analysis of 943 and 1792 subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Cancer (DPC) databases, respectively. The discrimination accuracy for BCR of seven previously published models was assessed using concordance index and compared with and without adding PSA nadir level in SEARCH. Using data from SEARCH, we developed a new nomogram incorporating PSA nadir to other known predictors (preoperative PSA, pathological Gleason score, PSA nadir level, surgical findings, prostate weight, body mass index and race) of BCR and externally validated it in the DPC.



Results: In SEARCH, the mean concordance index across all seven nomograms was 0.687. After the inclusion of PSA nadir, the concordance index increased by nearly 7% (mean=0.753). The concordance index of the new nomogram in SEARCH was 0.779 (bias-corrected=0.767), which was 5% better than the next best model. In DPC, the new nomogram yielded a concordance index of 0.778.



Conclusion: The addition of postoperative PSA nadir to commonly used nomograms increased their accuracies by nearly 7%. Based upon this, we developed and externally validated a new nomogram, which was well calibrated and highly accurate, and is a potentially valuable tool for patients and physicians to predict BCR after RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1320,

title = {Association of cigarette smoking with interval to biochemical recurrence after radical prostatectomy: results from the SEARCH database},

author = {D M Moreira and J A Antonelli and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/20381838/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=7},

doi = {10.1016/j.urology.2010.01.066 },

isbn = {1527-9995},

year  = {2010},

date = {2010-11-01},

journal = {Urology},

volume = {76},

number = {5},

pages = {1218-1223},

abstract = {Objectives: To analyze the association between cigarette smoking and biochemical recurrence (BCR) after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.



Methods: We performed a retrospective analysis of 1267 subjects from the SEARCH cohort treated from 1998 to 2008 with smoking status available from the preoperative notes. A comparison of the baseline patient and disease characteristics between the current smokers and nonsmokers (past and never smokers combined) was performed using the chi-square and rank sum tests. The univariate and multivariate associations between smoking status and BCR-free survival were analyzed using Kaplan-Meier plots, the log-rank test, and Cox proportional hazard models.



Results: Of the 1267 patients, 408 (32%) were active smokers and 859 (68%) were nonsmokers at surgery. The current smokers were younger (P < .001), more likely to be black (P < .001), and had a lower body mass index (P < .001), a greater percentage of positive biopsy cores (P = .039), a greater preoperative prostate-specific antigen level (P = .003), more extracapsular extension (P = .003) and seminal vesicle invasion (P = .029), and lower prostate volumes (P = .002). On univariate analysis, smokers had a risk of BCR similar to that of nonsmokers (hazard ratio 1.19, P = .129). On multivariate analysis, smoking was associated with an increased risk of BCR when adjusted for body mass index only (hazard ratio 1.37, P = .008). However, after adjustment for multiple preoperative characteristics, the association was attenuated and no longer statistically significant (hazard ratio 1.12, P = .325). After additional adjustment for postoperative features, such as tumor grade and stage, smoking was unrelated to the risk of BCR (hazard ratio 0.91, P = .502).



Conclusions: Among patients undergoing radical prostatectomy in the SEARCH cohort, cigarette smoking was associated with slightly more advanced disease but a similar risk of BCR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e131b,

title = {Glycemic control and prostate cancer progression: results from the SEARCH database},

author = {H S Kim and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/20687228/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=2},

doi = {10.1002/pros.21189 },

isbn = {1097-0045},

year  = {2010},

date = {2010-10-01},

journal = {The Prostate},

volume = {70},

number = {14},

pages = {1540-1546},

abstract = {Purpose: Several studies have examined the association between diabetes mellitus (DM) and prostate cancer (PCa) risk and progression, however nearly all of these studies have compared diabetic versus non-diabetic men. We sought to investigate the role of glycemic control, as measured by HbA1c, on PCa aggressiveness and prognosis in men with DM and PCa from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.



Methods: We identified 247 men in SEARCH with DM and a recorded HbA1c value within the 12 months prior to radical prostatectomy between 1988 and 2009. We divided these men into tertiles by HbA1c level. The associations between HbA1c tertiles and risk of adverse pathology and biochemical recurrence were tested using multivariate logistic regression and Cox proportional hazards models, respectively.



Results: Median HbA1c level was 6.9. On multivariate analysis, HbA1c tertiles were predictive of pathological Gleason score (P-trend = 0.001). Relative to the first tertile, men in the second (OR 4.68, P = 0.003) and third tertile (OR 6.60, P < 0.001) were more likely to have Gleason score > or = 4 + 3. HbA1c tertiles were not associated with margin status, node status, extracapsular extension or seminal vesicle invasion (all P-trend > 0.2). In the multivariate Cox proportional hazards model, increasing HbA1c tertiles were not significantly related to risk of biochemical recurrence (P-trend = 0.56).



Conclusion: Men with higher HbA1c levels presented with more biologically aggressive prostate tumors at radical prostatectomy. Although risk of recurrence was unrelated to HbA1c levels, further studies are needed to better explore the importance of glycemic control on long-term outcomes in diabetic men with PCa.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e131f,

title = {Outcomes after radical prostatectomy among men who are candidates for active surveillance: results from the SEARCH database},

author = {C J Kane and R Im and C L Amling and Presti J C Jr and W J Aronson and M K Terris and S J Freedland and SEARCH Database Study Group},

url = {https://pubmed.ncbi.nlm.nih.gov/20394969/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=6},

doi = {10.1016/j.urology.2009.12.073 },

isbn = {1527-9995},

year  = {2010},

date = {2010-09-01},

journal = {Urology},

volume = {76},

number = {3},

pages = {695-700},

abstract = {Objective: We sought to evaluate outcomes after radical prostatectomy among men with low-risk prostate cancer who would be candidates for active surveillance.



Methods: Using the Shared Equal Access Regional Cancer Hospital (SEARCH) database of men treated with radical prostatectomy at multiple equal-access medical centers between 1988 and 2007, 398 of 2062 men (19%) met our criteria for potential active surveillance: clinical stage T1c or T2a, prostate-specific antigen (PSA) <10 ng/mL, Gleason sum ≤6, and no more than 1 or 2 positive cores on at least a sextant biopsy. We examined the risk of adverse pathology, biochemical progression, and PSA doubling time (PSADT) at the time of recurrence. We used a Cox proportional hazards model to determine the significant predictors of PSA progression.



Results: Of the men with low-risk prostate cancer, 85% had organ-confined disease, only 2% had seminal vesicle invasion, and no patient had lymph node metastasis. The 5- and 10 year PSA-free survival rates were 81% (95% CI: 76-86%) and 66% (95% CI: 54-76%). On multivariate analysis, older age (P = .005), Agent Orange exposure (P = .02), and obesity (P = .03) were all significantly associated with biochemical failure. Mean and median PSADT among men who experienced recurrence were 37 and 20 months. Only 3 patients experienced recurrence with PSADT < 9 months.



Conclusions: Most men with low-risk prostate cancer treated with radical prostatectomy experience long-term PSA control. Those who did experience recurrence often did so with a long PSADT. Consistent with prior SEARCH database reports, older age, Agent Orange exposure, and obesity increased the risk of recurrence.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e131e,

title = {Statin medication use and the risk of biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database},

author = {R J Hamilton and L L Banez and W J Aronson and M K Terris and E A Platz and C J Kane and Presti J C Jr and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/20586112/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=5},

doi = {10.1002/cncr.25308 },

isbn = {0008-543X},

year  = {2010},

date = {2010-07-01},

journal = {Cancer},

volume = {116},

number = {14},

pages = {3389-3398},

abstract = {Background: Although controversial, evidence suggests statins may reduce the risk of advanced prostate cancer (PC), and recently statin use was associated with prostate-specific antigen (PSA) reductions among men without PC. The authors sought to examine the association between statin use and PSA recurrence after radical prostatectomy (RP).



Methods: The authors examined 1319 men treated with RP from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database. Time to PSA recurrence was compared between users and nonusers of statin at surgery using Cox proportional hazards models adjusted for multiple clinical and pathological features.



Results: In total, 236 (18%) men were taking statins at RP. Median follow-up was 24 months for statin users and 38 for nonusers. Statin users were older (P<.001) and underwent RP more recently (P<.001). Statin users were diagnosed at lower clinical stages (P=.009) and with lower PSA levels (P=.04). However, statin users tended to have higher biopsy Gleason scores (P=.002). After adjusting for multiple clinical and pathological factors, statin use was associated with a 30% lower risk of PSA recurrence (hazard ratio "HR", 0.70; 95% confidence interval "CI", 0.50-0.97; P=.03), which was dose dependent (relative to no statin use; dose equivalent<simvastatin 20 mg: HR, 1.08; 95% CI, 0.66-1.73; P=.78; dose equivalent=simvastatin 20 mg: HR, 0.57; 95% CI, 0.32-1.00; P=.05; dose equivalent>simvastatin 20 mg: HR, 0.50; 95% CI, 0.27-0.93; P=.03).



Conclusions: In this cohort of men undergoing RP, statin use was associated with a dose-dependent reduction in the risk of biochemical recurrence. If confirmed in other studies, these findings suggest statins may slow PC progression after RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1323,

title = {Re-calibration and external validation of an existing nomogram to predict aggressive recurrences after radical prostatectomy},

author = {F R Schroeck and M W Kattan and J W Moul and W J Aronson and Presti J C Jr and M K Terris and C J Kane and C L Amling and L Sun and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19912203/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=11},

doi = {10.1111/j.1464-410X.2009.09060.x },

isbn = {1464-410X},

year  = {2010},

date = {2010-06-01},

journal = {BJU international},

volume = {105},

number = {12},

pages = {1654-1659},

abstract = {Objective: To re-calibrate the previously published Duke Prostate Center (DPC) nomogram for the prediction of biochemical recurrence (BCR) after radical prostatectomy (RP) to not only predict overall BCR but also the clinically more relevant endpoint of an aggressive recurrence (i.e. a BCR with a postoperative PSA doubling time (PSADT) of <9 months).



Patients and methods: Using the established point-scale system based upon the previously published DPC nomogram, we re-calibrated this point system to predict not just BCR, but also aggressive BCR within 2599 men treated with RP from the DPC database. PSADT was computed on all patients meeting the recurrence definition who had a minimum of two PSA values, separated by at least 3 months, and < or =2 years after recurrence. External validation was performed using data from 1695 men treated with RP within the Shared Equal Access Regional Cancer Hospital (SEARCH) database by calculating the concordance index c and by plotting calibration curves.



Results: The median follow-up for patients with no BCR was 56 and 47 months for DPC and SEARCH, respectively. In the DPC modelling cohort and the SEARCH validation cohort, 645 (25%) and 557 (33%) men had BCR, while 83 (3.2%) and 71 (4.2%) patients had an aggressive recurrence. In external validation, predictive accuracy for an aggressive BCR was high (c = 0.83) and the nomogram showed good calibration.



Conclusions: We re-calibrated an existing nomogram to not only predict overall BCR after RP but also aggressive recurrence after RP. Our new tool can provide valuable information for patient counselling and patient selection for adjuvant therapy trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1324,

title = {Definition and preoperative predictors of persistently elevated prostate-specific antigen after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database},

author = {D M Moreira and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19912191/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=12},

doi = {10.1111/j.1464-410X.2009.09016.x [doi]},

isbn = {1464-410X},

year  = {2010},

date = {2010-06-01},

journal = {BJU international},

volume = {105},

number = {11},

pages = {1541-1547},

abstract = {Objectives: To define a level of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) that equates with high-risk for disease progression, and to identify preoperative predictors of PSA persistence among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.



Patients and methods: A total of 901 men treated with RP between 2001 and 2008 were separated into groups based upon PSA nadir within 6 months after RP. We explored the association between nadir groups and time to biochemical recurrence (BCR) using multivariate Cox proportional hazards and determined the preoperative predictors of PSA persistence using logistic regression.



Results: Relative to men with undetectable PSA levels, those with a PSA nadir of 0.03 (hazard ratio [HR] 3.88, P < 0.001), 0.04 (HR 4.87, P < 0.001), 0.05-0.09 (HR 12.69, P < 0.001), 0.1-0.19 (HR 13.17, P < 0.001), and 0.2 ng/mL (HR 13.23, P < 0.001) were at increased risk of BCR while men with a nadir of 0.01 (HR 1.36, P = 0.400) and 0.02 (HR 1.64, P = 0.180) were not. Using the PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, 230 men (26%) had persistence. The independent preoperative predictors of PSA persistence were higher body mass index (BMI, P = 0.002), pathological Gleason score (relative to 2-6: 4 + 3-10, P = 0.001) and preoperative PSA level (P < 0.001).



Conclusions: Men with a PSA nadir > or = 0.03 ng/mL after RP were at higher risk for BCR. Using a PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, persistence was predicted by known factors associated with aggressive disease (tumour grade, PSA level and BMI). Validation of the present definition in different populations using later end-points remains necessary to assess its prognostic usefulness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid20195294,

title = {Ŧhe influence of hepatic function on prostate cancer outcomes after radical prostatectomy},

author = {L L Ba?ez and R M Loftis and S J Freedland and J C Presti and W J Aronson and C L Amling and C J Kane and M K Terris},

url = {https://pubmed.ncbi.nlm.nih.gov/20195294/?from_term=FREEDLAND+KANE&from_sort=pubdate&from_size=100&from_pos=86},

doi = {10.1038/pcan.2010.3},

year  = {2010},

date = {2010-06-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {13},

number = {2},

pages = {173--177},

abstract = {Prostate growth is dependent on circulating androgens, which can be influenced by hepatic function. Liver disease has been suggested to influence prostate cancer (CaP) incidence. However, the effect of hepatic function on CaP outcomes has not been investigated. A total of 1181 patients who underwent radical prostatectomy (RP) between 1988 and 2008 at four Veterans Affairs hospitals that comprise the Shared Equal Access Regional Cancer Hospital database and had available liver function test (LFT) data were included in the study. Independent associations of LFTs with unfavorable pathological features and biochemical recurrence were determined using logistic and Cox regression analyses. Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) levels were elevated in 8.2 and 4.4% of patients, respectively. After controlling for CaP features, logistic regression revealed a significant association between SGOT levels and pathological Gleason sum > or =7(4+3) cancer (odds ratio=2.12; 95% confidence interval=1.11-4.05; P=0.02). Mild hepatic dysfunction was significantly associated with adverse CaP grade, but was not significantly associated with other adverse pathological features or biochemical recurrence in a cohort of men undergoing RP. The effect of moderate-to-severe liver disease on disease outcomes in CaP patients managed non-surgically remains to be investigated.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid19918263,

title = {Ŧhe effect of race on the discriminatory accuracy of models to predict biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Ħospital and Đuke Prostate Center databases},

author = {D M Moreira and J C Presti and W J Aronson and M K Terris and C J Kane and C L Amling and L L Sun and J W Moul and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19918263/?from_term=FREEDLAND+KANE&from_sort=pubdate&from_size=100&from_pos=88},

doi = {10.1038/pcan.2009.48},

year  = {2010},

date = {2010-03-01},

journal = {Prostate Cancer Prostatic Dis.},

volume = {13},

number = {1},

pages = {87--93},

abstract = {To evaluate whether race modifies the accuracy of nomograms to predict biochemical recurrence (BCR) after radical prostatectomy among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) and Duke Prostate Center (DPC) databases. Retrospective analysis of 1721 and 4511 subjects from the SEARCH and DPC cohorts, respectively. The discrimination accuracy for BCR of seven previously published predictive models was assessed using concordance index and compared between African-American men (AAM) and Caucasian men (CM). AAM represented 44% of SEARCH and 14% of DPC. In both cohorts, AAM were more likely to experience BCR than CM (P<0.01). In SEARCH, the mean concordance index across all seven models was lower in AAM (0.678) than CM (0.715), though the mean difference between CM and AAM was modest (0.037; range 0.015-0.062). In DPC the overall mean concordance index for BCR across all seven nomograms was 0.686. In contrast to SEARCH, the mean concordance index in DPC was higher in AAM (0.717) than CM (0.681), though the mean differences between CM and AAM was modest (-0.036; range -0.078 to -0.004). Across all seven models for predicting BCR, the discriminatory accuracy was better among CM in SEARCH and better among AAM in DPC. The mean difference in discriminatory accuracy of all seven nomograms between AAM and CM was approximately 3-4%. This indicates that currently used predictive models have similar performances among CM and AAM. Therefore, nomograms represent a valid and accurate method to predict BCR regardless of race.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1325,

title = {Freedom from a detectable ultrasensitive prostate-specific antigen at two years after radical prostatectomy predicts a favorable clinical outcome: analysis of the SEARCH database},

author = {S L Chang and S J Freedland and M K Terris and W J Aronson and C J Kane and C L Amling and Presti J C Jr},

url = {https://pubmed.ncbi.nlm.nih.gov/19819536/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=13},

doi = {10.1016/j.urology.2009.06.089 },

isbn = {1527-9995},

year  = {2010},

date = {2010-02-01},

journal = {Urology},

volume = {75},

number = {2},

pages = {439-444},

abstract = {Objectives: To assess the utility of kinetics for ultrasensitive prostate-specific antigen (uPSA) assays to identify men who are at risk of developing high-risk recurrent prostate cancer [prostate-specific antigen doubling time (PSADT) < 9 months] after radical prostatectomy. Previous studies demonstrate that a PSADT < 9 months after radical prostatectomy is associated with prostate cancer-specific mortality. Conventionally, PSADT has been calculated after biochemical failure (PSA > or = 2 0.2 ng/mL).



Methods: A review of the Shared Equal Access Regional Cancer Hospital database from 1988-2008 was performed to identify men with biochemical failure after radical prostatectomy and > or = 2 uPSA values before failure (PSA > or = 2 0.2 ng/mL) as well as > or = 2 2 values after failure to calculate PSADT. These patients were stratified into low-risk (PSADT > or = 2 9 months) and high-risk (PSADT < 9 months) cohorts. The following uPSA kinetics were analyzed for their ability to predict low- and high-risk cohorts: time to first detectable uPSA, time from uPSA to biochemical failure, uPSA velocity, uPSADT, uPSA exponential rise, and uPSA fluctuations.



Results: The analysis included 89 low- and 26 high-risk men. Time to first detectable uPSA was inversely associated with the high-risk cohort (OR 0.96, 95% CI 0.92-0.99, P = .02) and characterized by a high sensitivity and negative predictive value at a threshold of 2 years after surgery. Other measures of uPSA kinetics showed no association with PSADT.



Conclusions: Time to first detectable uPSA identifies men with low-risk recurrence prostate cancer. Patients with an undetectable uPSA 2 years after surgery are unlikely to develop PSADT < 9 months after biochemical failure.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1327,

title = {Estimated blood loss as a predictor of PSA recurrence after radical prostatectomy: results from the SEARCH database},

author = {J C Lloyd and L L Bañez and W J Aronson and M K Terris and Presti J C Jr and C L Amling and C J Kane and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19709073/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=14},

doi = {10.1111/j.1464-410X.2009.08792.x },

isbn = {1464-410X},

year  = {2010},

date = {2010-02-01},

journal = {BJU international},

volume = {105},

number = {3},

pages = {347-351},

abstract = {Objective: To clarify the relationship between estimated blood loss (EBL) and biochemical recurrence, assessed by prostate-specific antigen (PSA) level, as blood loss is a long-standing concern associated with radical prostatectomy (RP), and no studies to date have examined the association between blood loss and cancer control.



Patients and methods: In all, 1077 patients were identified in the Shared Equal-Access Regional Cancer Hospital database who underwent retropubic RP (between 1998 and 2008) and had EBL and follow-up data available. We examined the relationship between EBL and recurrence using multivariate Cox regression analyses.



Results: Increased EBL was correlated with PSA recurrence in a multivariate-adjusted model (P = 0.01). When analysed by 500-mL EBL categories, those with an EBL of <1500 mL had a similar risk of recurrence. However, the risk of PSA recurrence tended to increase for an EBL of 1500-3499 mL, before decreasing again for patients with an EBL of > or =3500 mL. Men with an EBL of 2500-3499 mL had more than twice the risk of recurrence than men with an EBL of <1500 mL (P = 0.02). EBL was not associated with adverse tumour stage, grade or margin status.



Conclusions: There was a significant correlation between EBL at the time of RP and biochemical recurrence. We hypothesized that this association might be due to transfusion-related immunosuppression, excessive blood obscuring the operative field, EBL being a marker of aggressive disease, or EBL being a marker of poor surgical technique. However, our data did not completely fit any one of these hypotheses, and thus the ultimate cause for the increased risk of recurrence remains unclear and requires further study.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1321,

title = {Diabetes and outcomes after radical prostatectomy: are results affected by obesity and race? Results from the shared equal-access regional cancer hospital database},

author = {J Jayachandran and W J Aronson and M K Terris and Presti J C Jr and C L Amling and C J Kane and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/20056618/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=9},

doi = {10.1158/1055-9965.EPI-09-0777 },

isbn = {1538-7755},

year  = {2010},

date = {2010-01-01},

journal = {Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology},

volume = {19},

number = {1},

pages = {9-17},

abstract = {Background: Diabetes is associated with lower prostate cancer risk. The association of diabetes with prostate cancer outcomes is less clear. We examined the association between diabetes and outcomes after radical prostatectomy and tested whether associations varied by race and/or obesity.



Materials and methods: This study is a retrospective analysis of 1,262 men treated with radical prostatectomy between 1988 and 2008 within the Shared Equal-Access Regional Cancer Hospital database. We examined the multivariate association between diabetes at surgery and adverse pathology, biochemical recurrence (BCR), and prostate-specific antigen doubling time at recurrence using logistic, proportional hazards, and linear regression, respectively. Data were examined as a whole and stratified by race and obesity.



Results: Diabetes was more prevalent among black (22% versus 15%, P < 0.001) and more obese men (P < 0.001). Diabetes was associated with higher tumor grade (odds ratio, 1.73; P = 0.002), seminal vesicle invasion (odds ratio, 1.73; P = 0.04), but not BCR (P = 0.67) or PSADT at recurrence (P = 0.12). In the secondary analysis, among white obese men, diabetes was associated with 2.5-fold increased BCR risk (P = 0.002) and a trend toward shorter PSADT, whereas among all other men (nonobese white men and black men), diabetes was associated with 23% lower recurrence risk (P = 0.09) and longer PSADT (P = 0.04).



Conclusion: In a radical prostatectomy cohort, diabetes was not associated with BCR. In the secondary analysis, diabetes was associated with more aggressive disease in obese white men and less aggressive disease for all other subsets. If externally validated, these findings suggest that among men with prostate cancer, the association between diabetes and prostate cancer aggressiveness may vary by race and obesity.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e132a,

title = {Predictors of secondary treatment following biochemical recurrence after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital database},

author = {D M Moreira and L L Bañez and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19522861/?from_term=freedland+kane&from_filter=years.2010-2010&from_sort=pubdate&from_size=100&from_pos=15},

doi = {10.1111/j.1464-410X.2009.08684.x },

isbn = {1464-410X},

year  = {2010},

date = {2010-01-01},

journal = {BJU international},

volume = {105},

number = {1},

pages = {28-33},

abstract = {Objective: To investigate the predictors of secondary treatment for recurrent prostate cancer after radical prostatectomy (RP) among subjects from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.



Patients and methods: We used Kaplan-Meier curves and Cox proportional hazard models to identify factors associated with time to secondary treatment and type of secondary treatment received among 697 men who developed biochemical recurrence (BCR) after RP.



Results: During a median follow-up of 45 months after BCR, 357 men received salvage treatment. The 1-, 3-, and 5-year risk of receiving any salvage treatment was 29% (95% confidence interval (CI) 26-33%), 48% (95%CI 44-52%), and 53% (95%CI 49-57%), respectively. In multivariate analysis, more recent year of recurrence, centre, shorter disease-free interval, and pathological high-grade disease (Gleason 8-10) predicted increased risk of salvage treatment (all P < 0.01). Predictors of specifically receiving radiotherapy were shorter disease-free interval, centre, and more recent year of BCR (all P < 0.001). Predictors of specifically receiving hormonal therapy were shorter disease-free interval, more recent year of BCR, centre, high Gleason score, and higher tumour stage (all P < 0.05). In a subset analysis of men with available prostate-specific antigen doubling time (PSADT) data, shorter PSADT predicted receipt of any salvage treatment as well as radiation and hormonal therapy separately. CONCLUSIONS; Among men who recur after RP, salvage treatment was associated with disease severity, centre and year of BCR; patient-specific factors (race, body mass index and age) were not predictive of secondary treatment. Although patients are being treated more aggressively in contemporary years, the affect on long-term survival is unknown.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1328,

title = {Does early prostate-specific antigen doubling time (ePSADT) after radical prostatectomy, calculated using PSA values from the first detectable until the first recurrence value, correlate with standard PSADT? A report from the Shared Equal Access Regional Cancer Hospital Database Group},

author = {A E Teeter and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19549124/?from_term=freedland+kane&from_filter=years.2009-2009&from_sort=pubdate&from_size=100&from_pos=8},

doi = {10.1111/j.1464-410X.2009.08680.x },

isbn = {1464-410X},

year  = {2009},

date = {2009-12-01},

journal = {BJU international},

volume = {104},

number = {11},

pages = {1604-1609},

abstract = {Objective: To determine if prostate-specific antigen doubling time (PSADT), calculated from the first detectable PSA level after radical prostatectomy (RP) to the first PSA level of >or=0.2 ng/mL (early PSADT or ePSADT), correlated with 'standard' PSADT (henceforth PSADT) calculated using values >or=0.2 ng/mL, as a short PSADT following biochemical recurrence (BCR) after RP portends a poor prognosis and poor response to salvage treatment but this is based upon PSADT calculated using PSA values of >or=0.2 ng/mL.



Patients and methods: We used Spearman's correlation to determine the correlation between ePSADT and PSADT among 157 men in the Shared Equal Access Regional Cancer Hospital database who underwent RP between 1988 and 2005 and had a calculable ePSADT and PSADT. We systematically examined ePSADT thresholds and their positive and negative predictive values (PPV and NPV, respectively), to predict aggressive recurrences (PSADT of <9 months).



Results: ePSADT was significantly, though poorly, correlated with PSADT (r = 0.30, P < 0.001). ePSADT more accurately predicted PSADT among men with a long ePSADT. Of men with an ePSADT of >or=20 or >or=15 months, the NPV for an aggressive recurrence was 98% and 93%, respectively. However, among men with an ePSADT of <3 months, the PPV for aggressive recurrence was only 39%.



Conclusions: Although ePSADT and PSADT were significantly related, the overall correlation was poor. This was highlighted by the finding that only 39% of men with the shortest ePSADT (<3 months) had a PSADT of <9 months. However, a long ePSADT correlated well with a long PSADT and is thus useful in identifying men at low risk for prostate cancer-specific mortality very early in their BCR.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1322,

title = {Obesity as a predictor of adverse outcome across black and white race: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database},

author = {J Jayachandran and L L Bañez and W J Aronson and M K Terris and Presti J C Jr and C L Amling and C J Kane and S J Freedland and SEARCH Database Study Group},

url = {https://pubmed.ncbi.nlm.nih.gov/19670453/?from_term=freedland+kane&from_filter=years.2009-2009&from_sort=pubdate&from_size=100&from_pos=2},

doi = {10.1002/cncr.24571 },

isbn = {0008-543X},

year  = {2009},

date = {2009-11-01},

journal = {Cancer},

volume = {115},

number = {22},

pages = {5263-5271},

abstract = {Background: Across multiple studies, obesity has been associated with an increased risk of higher grade disease and prostate-specific antigen (PSA) recurrence after radical prostatectomy (RP). Whether these associations vary by race is unknown. In the current study, the authors examined the association between obesity and outcome after RP stratified by race.



Methods: A retrospective analysis was performed on 1415 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) database who underwent RP between 1989 and 2008. The association between increased body mass index (BMI) and adverse pathology and biochemical recurrence was examined using multivariate logistic regression and Cox models, respectively. Data were examined stratified by race.



Results: After adjusting for preoperative clinical characteristics, higher BMI was associated with higher tumor grade (P = .008) and positive surgical margins (P < .001) in white men, and similar but statistically nonsignificant trends were observed in black men. No significant interaction was noted between race and BMI for associations with adverse pathology (P(interaction)> or =.12). After adjusting for preoperative clinical characteristics, higher BMI was associated with an increased risk of recurrence in both white men (P = .001) and black men (P = .03). After further adjusting for pathologic variables, higher BMI was associated with significantly increased risk of recurrence in white men (P = .002) and black men (P = .01). No significant interactions were observed between race and BMI for predicting biochemical progression adjusting either for preoperative factors (P(interaction) = .35) or for preoperative and pathologic features (P(interaction) = .47).



Conclusions: Obesity was associated with a greater risk of recurrence among both black men and white men. Obesity did not appear to be more or less influential in 1 race than another but, rather, was identified as a risk factor for aggressive cancer regardless of race.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1326,

title = {Natural history of persistently elevated prostate specific antigen after radical prostatectomy: results from the SEARCH database},

author = {D M Moreira and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19758614/?from_term=freedland+kane&from_filter=years.2009-2009&from_sort=pubdate&from_size=100&from_pos=6},

doi = {10.1016/j.juro.2009.07.022 },

isbn = {1527-3792},

year  = {2009},

date = {2009-11-01},

journal = {The Journal of Urology},

volume = {182},

number = {5},

pages = {2250-2255},

abstract = {Purpose: We examined natural history, predictors of biochemical recurrence and all cause mortality in patients with persistently elevated prostate specific antigen after radical prostatectomy in the Shared Equal Access Regional Cancer Hospital cohort.



Materials and methods: We reviewed data on 1,156 men treated with radical prostatectomy after 1997. Prostate specific antigen persistence was defined as failure to achieve prostate specific antigen less than 0.03 ng/ml within 6 months postoperatively. Disease-free and overall survival was compared between men with and without persistence using the log rank test. Predictors of biochemical recurrence and all cause death were analyzed using the Cox model.



Results: A total of 291 men (25%) had persistence, which was associated with increased biochemical recurrence and all cause death (p <0.001 and 0.041, respectively). In patients with persistence 1 and 5-year biochemical recurrence-free survival was 68% and 36%, significantly lower than 95% and 72%, respectively, in men without persistence. Ten-year overall survival in patients with vs without persistence was 63% vs 80%. In men with persistence independent predictors of prostate specific antigen recurrence were higher prostate specific antigen nadir (HR 2.19, p <0.001), positive surgical margins (HR 1.75, p = 0.022) and high pathological Gleason score (8-10 vs 2-6 HR 2.40, p = 0.026). Independent predictors of overall mortality were a higher prostate specific antigen nadir (HR 1.46, p = 0.013) and seminal vesicle invasion (HR 3.15, p = 0.047).



Conclusions: Prostate specific antigen persistence is associated with increased biochemical recurrence and overall mortality. In men with persistence the prostate specific antigen nadir is an independent predictor of recurrence and mortality. Thus, prostate specific antigen persistence and nadir are important tools for early postoperative risk stratification.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e132b,

title = {Validation of a nomogram to predict disease progression following salvage radiotherapy after radical prostatectomy: results from the SEARCH database},

author = {D M Moreira and J Jayachandran and Presti J C Jr and W J Aronson and M K Terris and C J Kane and C L Amling and A J Stephenson and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19466946/?from_term=freedland+kane&from_filter=years.2009-2009&from_sort=pubdate&from_size=100&from_pos=11},

doi = {10.1111/j.1464-410X.2009.08623.x },

isbn = {1464-410X},

year  = {2009},

date = {2009-11-01},

journal = {BJU international},

volume = {104},

number = {10},

pages = {1452-1456},

abstract = {Objective: To externally validate the nomogram published by Stephenson et al. (termed the 'Stephenson nomogram') to predict disease progression after salvage radiotherapy (SRT) among patients with prostate cancer from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.



Patients and methods: We analysed data from 102 men treated with SRT for prostate-specific antigen (PSA) failure after prostatectomy, of whom 30 (29%) developed disease progression after SRT during a median follow-up of 50 months. The predicted 6-year progression-free survival (PFS) was compared to the actuarial PFS using calibration plots. The accuracy of the nomogram to risk-stratify men for progression was assessed by the concordance index.



Results: The median PSA and PSA doubling time before SRT was 0.6 ng/mL and 10.3 months, respectively. The 6-year actuarial disease-free progression after SRT was 57% (95% confidence interval 42-69%). The overall concordance index of the Stephenson nomogram was 0.65. The nomogram predicted failure more accurately at the extremes of risk (lowest and highest) but in intermediate groups, the accuracy was less precise. Of the 11 variables used in the nomogram, only negative margins and high PSA level before SRT were significantly associated with increased disease progression.



Conclusion: The Stephenson nomogram is an important tool to predict disease progression after SRT following radical prostatectomy. It adequately predicted progression in SEARCH with reasonable accuracy. Also, in SEARCH, disease progression was predicted by similar disease characteristics. However, the overall modest performance of the model in our validation cohort indicates there is still room for improvement in predictive models for disease progression after SRT.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e1329,

title = {Body mass index and prostate specific antigen as predictors of adverse pathology and biochemical recurrence after prostatectomy},

author = {L L Bañez and L Sun and B J Trock and M Han and A W Partin and W J Aronson and M K Terris and Presti J C Jr and C J Kane and C L Amling and J W Moul and S J Freedland},

url = {https://pubmed.ncbi.nlm.nih.gov/19524974/?from_term=freedland+kane&from_filter=years.2009-2009&from_sort=pubdate&from_size=100&from_pos=9},

doi = {10.1016/j.juro.2009.04.007 },

isbn = {1527-3792},

year  = {2009},

date = {2009-08-01},

journal = {The Journal of urology},

volume = {182},

number = {2},

pages = {491-8},

abstract = {Purpose: Preoperative prostate specific antigen is widely used to predict unfavorable pathological features and biochemical relapse after radical prostatectomy. Recent reports that hemodilution may be responsible for lower prostate specific antigen in obese men led to concerns that prostate specific antigen may be less effective for prognosticating in men with increased body mass index. We determined whether the clinical usefulness of prostate specific antigen is negatively impacted by obesity by examining its operating characteristics and predictive accuracy as a function of body mass index.



Materials and methods: We performed a multicenter retrospective analysis of the records of 11,705 men who underwent radical prostatectomy from 1988 to 2007 from Veterans Affairs hospitals of the Shared Equal Access Regional Cancer Hospital Database, the Duke Prostate Center and Johns Hopkins Hospital. ROC curve analysis, the concordance index and the test for interaction were used to compare the ability of prostate specific antigen to predict unfavorable tumor characteristics and biochemical recurrence across body mass index categories.



Results: There were no significant differences in the area under ROC curves across increasing body mass index categories for prostate specific antigen to predict pathological Gleason sum (7 or greater, 7 [4 + 3] or greater, or 8 or greater), positive surgical margins, extracapsular extension or seminal vesicle invasion in all 3 cohorts. There was no significant difference in prostate specific antigen accuracy to predict biochemical failure across increasing body mass index categories.



Conclusions: In 3 cohorts of men treated with radical prostatectomy the ability of preoperative prostate specific antigen to predict adverse pathological features and posttreatment biochemical recurrence is not significantly affected by obesity. However, adjusting for obesity related hemodilution may still be required to properly interpret prostate specific antigen results in men with increased body mass index.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{RefWorks:doc:5ecea39ae4b07076c88e132d,

title = {Exposure to Agent Orange is a significant predictor of prostate-specific antigen (PSA)-based recurrence and a rapid PSA doubling time after radical prostatectomy},

author = {S R Shah and S J Freedland and W J Aronson and C J Kane and Presti J C Jr and C L Amling and M K Terris},

url = {https://pubmed.ncbi.nlm.nih.gov/19298411/?from_term=freedland+kane&from_filter=years.2009-2009&from_sort=pubdate&from_size=100&from_pos=13},

doi = {10.1111/j.1464-410X.2009.08405.x },

isbn = {1464-410X},

year  = {2009},

date = {2009-05-01},

journal = {BJU international},

volume = {103},

number = {9},

pages = {1168-1172},

abstract = {Objective: To investigate and report the clinicopathological characteristics and outcomes after radical prostatectomy (RP) in patients with prostate cancer and previous exposure to Agent Orange (AO), particularly in relationship to race.



Patients and methods: In 1495 veterans who had undergone RP the clinicopathological characteristics, biochemical progression rates, and prostate-specific antigen (PSA) doubling time (DT) after recurrence between AO-exposed and unexposed men were compared using logistic and linear regression and Cox proportional hazards analyses, and stratified by race.



Results: The 206 (14%) men with AO exposure were more likely to be black (P = 0.001), younger (P < 0.001), treated more recently (P < 0.001), have a higher body mass index (P = 0.001), have clinical stage T1 disease (P < 0.001), and have lower preoperative PSA levels (P = 0.001). After adjusting for several clinical characteristics, AO exposure was not significantly related to adverse pathological features but was significantly associated with biochemical progression risk (relative risk 1.55, 95% confidence interval 1.15-2.09, P = 0.004) and shorter PSADT (P < 0.001) after recurrence (8.2 vs 18.6 months). When stratified by race, these associations were present and similar in both races, with no significant interaction between race and AO exposure for predicting biochemical recurrence or mean adjusted PSADT (P interaction >0.20).



Conclusions: Patients with AO exposure and treated with RP were more likely to be black, present with lower risk features, have an increased risk of biochemical progression, and shorter PSADT after recurrence. When stratified by race, the association between AO exposure and poor outcomes was present in both races. These findings suggest that among selected men who choose RP, AO exposure might be associated with more aggressive prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}