Conference Abstracts

@article{Patel2020,

title = {PD16-10 RACE DOES NOT PREDICT SKELETAL RELATED EVENTS AND ALL-CAUSE MORTALITY IN MEN WITH CASTRATE RESISTANT PROSTATE CANCER},

author = {Devin Patel and Lauren Howard and Christopher L Amling and William Aronson and Zachary Klaassen and Martha Terris and Christopher Kane and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1097/JU.0000000000000859.010},

doi = {https://doi.org/10.1097/JU.0000000000000859.010},

year  = {2020},

date = {2020-04-01},

journal = {Journal of the American Urological Association},

volume = {203},

number = {4},

pages = {e367},

abstract = {INTRODUCTION AND OBJECTIVE:

Owing to its effects on both hematopoiesis and bone structure, metastasis to bone is a major cause of morbidity for patients with advanced prostate cancer. Despite the well-known differences between race, bone health and cancer survivorship, the impact of race on prostate cancer skeletal related events (SRE) remains understudied. Our objective was to study the impact of race on time to SRE and overall survival in men with newly diagnosed bone metastatic castration resistant prostate cancer (mCRPC).



METHODS:

We performed a retrospective study of patients newly diagnosed with bone mCRPC in the year 2000 or later from eight Veterans Affairs Medical Centers. SREs were comprised of pathologic fracture, spinal cord compression, radiation to the bone, or surgery to the bone. Time from bone mCRPC to SRE and overall mortality was estimated by the Kaplan-Meier method. Cox proportional hazards regression models were used to test the association between race, SREs and overall mortality.



RESULTS:

Of the 837 patients with bone mCRPC, 232 (27.7%) were black and 605 (72.3%) were nonblack. At the time of bone mCRPC diagnosis, black patients were more likely to have a higher number of bone metastases than nonblack men (29% vs. 19% with ≥10 bone metastases; p=0.021), have a higher PSA (41.7 vs. 29.2 ng/ml; p=0.005) and a longer time from CRPC to metastasis diagnosis (17.9 vs. 14.3 months; p<0.01). On multivariable analysis, there were no differences in the risk of developing a SRE between black and nonblack patients (HR,0.89; p=0.13). Similarly, there were no differences in overall mortality between black and nonblack men with bone mCRPC (HR, 0.87; p=0.13).



CONCLUSIONS:

We observed no association between racial differences and the development of SREs and overall mortality, indicating that once men have a diagnosis of bone mCRPC, race may not be a prognostic factor. These data suggest that the greatest benefits to understanding racial disparities in prostate cancer would occur if efforts are focused on cancer development and progression in early stage disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Daskivich2020,

title = {PD13-04 LONG-TERM COMPETING RISKS OF MORTALITY AMONG MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY},

author = {Timothy Daskivich and Lauren Howard and Christopher Amling and William Aaronson and Matthew R Cooperberg and Christopher Kane and Zachary Klaassen and Martha Terris and Stephen J Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1097/JU.0000000000000847.04},

doi = {https://doi.org/10.1097/JU.0000000000000847.04},

year  = {2020},

date = {2020-04-01},

journal = {Journal of the American Urological Association},

volume = {203},

number = {4},

pages = {e267},

abstract = {INTRODUCTION AND OBJECTIVE:

Men with biochemical recurrence (BCR) after radical prostatectomy (RP) have little information on long-term competing risks of mortality to inform prognosis and guide treatment decisions. We sought to identify predictors of prostate cancer metastasis and mortality (PCSM) and other-cause mortality (OCM) and to quantify long-term mortality outcomes across these key clinical predictors.



METHODS:

We analyzed 1,225 men with BCR after RP from 2001–2017 in the VA Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable competing risks regression analysis was used to identify predictors of metastasis, PCSM, and OCM and to quantify cumulative incidence of these outcomes over time. Recursive partitioning analysis was used to identify optimum variable cutpoints for prediction of PCSM and OCM.



RESULTS:

Of the 1,225 men in our sample, 243 (20%) died of other causes and 68 (6%) died of prostate cancer over a median follow up of 5.6 years (IQR 2.7, 9.1) after BCR. Multivariable competing risks regression showed that higher preoperative D’Amico tumor risk and PSA-DT at BCR <9 months were significantly associated with both metastasis and PCSM (all p≤0.001); for example, men with PSA-DT at BCR < 9 months had 16% and 9% probability of metastasis and PCSM at 10 years, respectively. Advanced age and worse comorbidity burden were significantly associated with OCM (both p≤0.001); for example, cumulative incidence of 10-year OCM was substantially higher among men 70 years or older with CCI 1 (45%), 2 (40%), or 3+ (49%) compared with those with CCI 0 (20%). RPA identified optimal variable cutpoints for prediction of PCSM—PSA at recurrence (<10 vs. ≥10 ng/ml), D’Amico tumor risk (low/intermediate vs. high), and PSA doubling time (<9 vs. ≥9 months)—with the highest risk subgroup having 10-year PCSM of 21% (Figure). RPA identified optimal variable cutpoints for prediction of OCM—age at BCR (<70 vs. ≥70 years), and CCI at BCR (for those <70, CCI<2 vs. ≥2; for those ≥70, CCI0 vs. ≥1)—with the highest risk subgroup having 10-year OCM of 50% (Figure).



CONCLUSIONS:

Readily available clinical predictors such as PSA and PSA-DT at BCR, preoperative D’Amico tumor risk, age, and CCI can robustly stratify long-term risk of metastasis, PCSM, and OCM in men with BCR after RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kuhlmann2020,

title = {PD62-08 PREDICTED RISK OF PROSTATE CANCER-SPECIFIC MORTALITY ON ACTIVE SURVEILLANCE FOR MEN WITH FAVORABLE INTERMEDIATE RISK PROSTATE CANCER: RESULTS FROM THE SEARCH DATABASE},

author = {Paige K. Kuhlmann and Taofik Oyekunle and Lauren Howard and Zachary Klaassen and Christopher L Amling and William Aronson and Matthew R Cooperberg and Christopher J Kane and Martha K Terris and Stephen J. Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1097/JU.0000000000000979.08},

doi = {https://doi.org/10.1097/JU.0000000000000979.08},

year  = {2020},

date = {2020-04-01},

journal = {Journal of the American Urological Association},

volume = {203},

number = {4},

pages = {e1289},

abstract = {INTRODUCTION AND OBJECTIVE:

Limited data exist to help surgeons decide between active surveillance (AS) vs. treatment for men with favorable intermediate risk (FIR) prostate cancer (PC). Ten-year results from a large randomized controlled trial (ProtecT) including men with low risk and FIR disease on AS versus treatment reported a non-significant 1.7 fold increase in PC-specific mortality (PCSM) for AS, though most men were low risk. To determine the excess risk of PCSM with AS vs. radical prostatectomy (RP), we determined the risk of PCSM in FIR men undergoing RP and estimated the PCSM risk for AS using a range of increased PSCM scenarios ranging from 50% higher to 5-fold higher.



METHODS:

We retrospectively reviewed data from men undergoing RP from 1988-2017 at 8 Veterans Affairs hospitals within the SEARCH Database. Men with FIR PC were identified using the NCCN risk criteria (<50% positive biopsy cores & cT2b-c or grade group (GG) 2 or PSA 10-20). Risk of PCSM at 5, 10, and 15 years after RP was estimated. Using these estimates, PCSM and number needed to harm (NNH) at 5, 10, and 15 years was then estimated for AS using a range of increased risk of PCSM relative to RP ranging from 50% higher to 5-fold higher.



RESULTS:

For the 920 FIR men identified, 5-, 10-, and 15-year survival estimates for PCSM were 99.86%, 99.01%, and 97.63%, respectively. Using these estimates, if the risk of PCSM on AS were 1.5 times greater than RP, for 15 year survival 92 patients would need to be put on AS for 1 excess PC-specific death to occur (1.09% excess risk of PCSM). If the risk of PCSM on AS were 5 times greater than RP, for 15 year survival the NNH would be 12 (8.68% excess risk of PCSM). Tables 1a&b summarize NNH and risk of excess PCSM assuming AS has 1.5, 2, 3, and 5 times the risk of PCSM relative to RP.



CONCLUSIONS:

The risk of death for FIR after RP is very low. Assuming even modest increases PCSM with AS vs. RP, the excess risk of death for AS in FIR is low. 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{Kelkar2020,

title = {MP37-08 THE ASSOCIATION BETWEEN DIABETES AND PROSTATE CANCER-SPECIFIC MORTALITY IS DIFFERENT IN OBESE AND NON-OBESE MEN AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE},

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

url = {https://www.auajournals.org/doi/pdf/10.1097/JU.0000000000000886.08},

doi = {https://doi.org/10.1097/JU.0000000000000886.08},

year  = {2020},

date = {2020-04-01},

journal = {Journal of the American Urological Association},

volume = {203},

number = {4},

pages = {e562-e563},

abstract = {INTRODUCTION AND OBJECTIVE:

We previously reported that in obese men, diabetes increased the risk of metastasis after radical prostatectomy (RP) whereas no such link was seen in non-obese men. Moreover, in diabetics, duration of diabetes was linked with an increased metastasis risk. In this larger study with longer follow-up, we tested associations between diabetes and prostate cancer-specific mortality (PCSM), metastases, and castrate resistant PC (CRPC), and if these associations differed by obesity status.



METHODS:

Men who had undergone RP at six Veterans Affairs Medical Centers between 1988-2017 were analyzed in the SEARCH database. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) using Cox models adjusted for age, race, BMI, pre-RP PSA, surgery year, surgical center, clinical stage, margins status, extracapsular extension, seminal vesicle invasion, lymph node status, and pathological grade group. The associations between diabetes and PCSM, CRPC and metastases were determined in the entire cohort and stratified by obesity (BMI: non-obese <30 kg/m2; obese ≥30 kg/m2). Interactions between obesity and diabetes were evaluated in fully adjusted models.



RESULTS:

Of 4688 men identified, 20% (n=955) were diabetic and 33% (n=1560) were obese at RP. During a median follow-up of 8 years, 102 men had PCSM, 133 had CRPC and 201 had metastases. In adjusted models, in obese men, diabetes was associated with increased PCSM (HR=3.56; 95%CI: 1.69-7.54), CRPC (HR=2.46; 95%CI: 1.28-4.72), and metastases (HR=1.69; 95%CI: 0.99-2.90), although the HR for metastases was not statistically significant. In non-obese men, all associations between diabetes and outcomes were null. The interaction terms for diabetes and obesity were statistically significant for PCSM (p=0.002), CRPC (p=0.004) and metastases (p=0.012).



CONCLUSIONS:

Our findings suggest that following RP, diabetes is a risk factor for PC progression and mortality in obese men, but not non-obese men. If confirmed in future studies, understanding the mechanistic underpinnings for these associations may shed important light on PC tumor biology.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Tablazon2019,

title = {MP34-10 PREDICTORS OF SKELETAL RELATED EVENTS AND OVERALL MORTALITY IN MEN WITH METASTATIC, CASTRATION-RESISTANT PROSTATE CANCER: RESULTS FROM THE SEARCH DATABASE},

author = {Ingrid Lorese Tablazon and Lauren Howard and Amanda De Hoedt and William Aronson and Christopher Kane and Christopher Amling and Matthew Cooperberg and Martha Terris and Stephen Freedland and Stephen Williams },

url = {https://www.auajournals.org/doi/pdf/10.1097/01.JU.0000555900.94072.95},

doi = {https://doi.org/10.1097/01.JU.0000555900.94072.95},

year  = {2019},

date = {2019-04-01},

journal = {Journal of Urology},

volume = {201},

number = {4S},

pages = {499},

abstract = {INTRODUCTION AND OBJECTIVES:

Although skeletal related events (SREs) are linked with reduced quality of life and worse health outcomes, the factors that predict SREs are poorly established. We aimed to identify predictors of SREs and all-cause mortality among men with metastatic, castration-resistant prostate cancer (mCRPC).



METHODS:

We retrospectively reviewed data on 863 men initially diagnosed with non-metastatic CRPC who later developed bone metastasis (mCRPC) at 8 VA centers within SEARCH from 2000-2017. Patients were followed to assess development of SREs (pathological fracture, radiation to the bone, spinal cord compression, and surgery to the bone). We used model selection with Cox models to evaluate predictors of SREs and overall mortality. Candidate covariates included race, age and PSA at metastases, year of metastases, treatment center, biopsy grade group, primary localized treatment, number of bone metastases, bone pain, PSA doubling time, presence of lymph node metastasis or visceral metastasis, months from ADT to CRPC, and months from CRPC to metastasis.



RESULTS:

Median (IQR) age at mCRPC was 76 (69-83) and 28% were black. 362 (43%) men reported bone pain and 44 (5%) had visceral metastasis at time of mCRPC. Of 863 men with bone mCRPC, 287 had an SRE (33%), and 740 (85%) died. 236 of the 287 (83%) who developed an SRE had bone radiation. Bone pain was the strongest predictor of SRE (Hazard Ratio (HR) 3.00, 95% Confidence Interval (CI), 2.27-3.96). Shorter time from CRPC to metastasis (HR 0.91), shorter time from ADT to CRPC (HR 0.94), and presence of visceral metastasis (HR 1.83) were significantly associated with increased SRE. Bone metastases ≥10 (HR 2.18, 95% CI, 1.73-2.75) was the strongest predictor for mortality. Moreover, receiving primary localized treatment (specifically radical prostatectomy vs. no treatment) (HR 0.74), shorter time from ADT to CRPC (HR 0.97), earlier year of metastasis (HR 0.98), older age (HR 1.02), higher PSA at metastasis (HR 1.20), bone pain (HR 1.44), the presence of visceral metastasis (HR 1.72), were significantly associated with increased risk of mortality.



CONCLUSIONS:

Among men with bone mCRPC, bone pain was the strongest predictor for SRE and the number of bone metastases at mCRPC diagnosis was the strongest predictor for all-cause mortality. If validated in future studies, these factors may be used to risk stratify patients. Future studies are needed to investigate the relationship between bone pain and the development of pathological fractures and spinal cord compression.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Zhao2019,

title = {MP34-13 COMBINATION THERAPY WITH RADIUM-223 AND ABIRATERONE OR ENZALUTAMIDE IN A LARGE REAL WORLD COHORT},

author = {Hanson Zhao and Lauren Howard and Amanda De Hoedt and Martha Terris and Christopher Amling and Christopher Kane and Matthew Cooperberg and William Aronson and Thomas Polascik and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1097/01.JU.0000555897.09320.ac},

doi = {https://doi.org/10.1097/01.JU.0000555897.09320.ac},

year  = {2019},

date = {2019-04-01},

journal = {Journal of Urology},

volume = {201},

number = {4S},

pages = {500},

abstract = {INTRODUCTION AND OBJECTIVES:

Combination therapies for metastatic castration resistant prostate cancer (mCRPC) are currently being investigated. Recently, the phase III ERA-223 trial was unblinded due to an increased incidence of deaths and bone fractures in the radium-223 with abiraterone arm compared to the placebo plus abiraterone arm. Using a large, real-world cohort, we aimed to evaluate the risk of all-cause mortality (ACM) and skeletal related events (SRE) among men who received radium-223 with or without abiraterone/enzalutamide.



METHODS:

We reviewed charts of all men with mCRPC in the entire Veterans Affairs (VA) system alive as of January 1st, 2013 who received radium-223. Cox models were used to test the association between concomitant radium-223 use with abiraterone/enzalutamide on ACM and SRE vs. radium-223 alone. Four sensitivity analyses were done: (1) men with 30 days of treatment overlap, (2) men with 60 days of overlap, (3) men who received intermittent radium, defined as less than an average of 0.8 infusions/month, and (4) men stratified by use of denosumab/bisphosphonate at radium-223 start.



RESULTS:

116/318 (37%) men were taking abiraterone or enzalutamide at the same time as radium-223. On univariable and multivariable analysis, there was no significant difference in ACM between men who did and did not receive abiraterone/enzalutamide while on radium-223 (p=0.33). Similarly, there was no difference in time to SRE in men on concomitant abiraterone/enzalutamide (p=0.88). There was no difference in ACM for any of the sensitivity analyses, but there was a trend to increased SRE risk in men who had 30 days of therapy overlap (p=0.051) and men who received radium at regular intervals (p=0.064). There was no association with ACM or SRE after stratifying by use of denosumab /bisphosphonates.



CONCLUSIONS:

Despite the common use of combination therapy, there was no increased ACM risk. There was a trend to increased SRE risk in some subgroups, but this was not significant. Further work needs to evaluate the optimal sequence and timing of combination therapies with a focus on safety profile.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vaculik2019,

title = {MP54-14 TIME TRENDS IN USE OF RADICAL PROSTATECTOMY BY TUMOR RISK AND LIFE EXPECTANCY IN A NATIONAL VA COHORT FROM 2000 TO 2017},

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

url = {https://www.auajournals.org/doi/pdf/10.1097/01.JU.0000556681.16460.b3},

doi = {https://doi.org/10.1097/01.JU.0000556681.16460.b3},

year  = {2019},

date = {2019-04-01},

journal = {Journal of Urology},

volume = {201},

number = {4S},

pages = {789-790},

abstract = {INTRODUCTION AND OBJECTIVES:

Current prostate cancer (PC) treatment guidelines endorse active surveillance (AS) for most men with low-risk PC and select men with favorable intermediate-risk PC among those with ≥10-year life expectancy (LE), while recommending observation (or non-surgical management) for those with <10-year LE. We sought to identify time trends in the use of radical prostatectomy (RP) for non-metastatic PC across subgroups of tumor risk and LE.



METHODS:

We sampled 4,902 men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database treated with radical prostatectomy for non-metastatic PC at 8 Veterans Affairs hospitals between 2000 and 2017. LE was calculated using age and Charlson comorbidity index scores. Stratified linear regression was used to calculate trends in proportion of men treated with RP by D'Amico tumor risk and LE (≥10 vs. <10 years) subgroups.



RESULTS:

Across all men, from 2000 to 2017, the proportion of low-risk tumors treated with RP decreased from 51% to 8% (43% decrease, 95% CI -50% to -37%, p<0.001), while the proportion of intermediate- and high-risk tumors increased from 32% to 60% (28% increase, 95% CI 24% to 32%, p<0.001) and 17% to 33% (16% increase, 95% CI 9% to 23%, p=0.002), respectively. The proportion of favorable intermediate-risk tumors treated with RP decreased from 67% to 40% over the study period (27% decrease, 95% CI -47% to -6%, p=0.01). Among men older than 65 (n=1,398/4,902 (29%)), the proportion treated with RP did not differ over time between those with <10-year LE (44% to 49%, 5% increase, 95% CI -4% to 14%, p=0.2) and those with ≥10-year LE (56% to 51%, 5% decrease, 95% CI -14% to 4%, p=0.2). There was also no statistically significant difference in proportion treated with RP over time between men with <10 vs. ≥10-year LE within any tumor risk subgroup. However, the proportion treated with RP for favorable intermediate-risk disease appeared to decrease less markedly over time in men with <10-year LE compared with ≥10-year LE (9% decrease vs. 44% decrease, p=0.07).



CONCLUSIONS:

While VA urologists now are operating infrequently on low-risk tumors, rates of RP among men with limited LE appear to be stable over time. LE should play a greater role in triage and management of men with indolent PC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Radium-223 treatment patterns in a large real-world population.},

author = {Hanson Hanqing Zhao and Lauren Howard and Amanda Hoedt and Martha K Terris and Christopher L. Amling and Christopher J. Kane and Matthew R. Cooperberg and William J. Aronson and Thomas Polascik and Stephen J. Freedland},

doi = {https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.190},

year  = {2019},

date = {2019-02-01},

urldate = {2019-02-01},

journal = {Journal of Clinical Oncology},

volume = {37},

number = {7},

pages = {190},

abstract = {Background: For men with symptomatic metastatic castration resistant prostate cancer (mCRPC), radium-223 was shown to improve overall survival in the phase III, double blind ALSYMPCA trial. Despite the observed benefits, the application and practice patterns of Radium-223 outside of clinical trials are largely unknown. Here we aim to better characterize the use of radium-223 in a large and heterogeneous real-world population. We identify treatment patterns associated with radium-223 and link these patterns with time to skeletal related event (SRE) and mortality. 

 

Methods: We reviewed charts of all men with diagnosed with mCRPC in the entire Veterans Affairs (VA) system alive as of January 1, 2013 who received radiun-223. We generated Kaplan Meier curves for survival and time to SRE based on treatment patterns. We examined the association between common treatment patterns and mortality and time to SRE with Cox models. 

 Results: We identified 318 men with bone mCRPC who received radium-223. Median age at radium start was 69 ys and median follow up was 25.3 months. Median survival was 11 months. 277 patients died during the study period (87%). 50% (158/318) completed ≤4 injections. There was a significant difference mortality among four consolidated treatment patterns (p=0.005) and but no difference SRE (p=0.10). On univariable and multivariable analysis, men who received AR target + docetaxel + radium-223 had increased mortality vs. men who received AR target + radium-223 (p=0.010 and 0.005, respectively). Multivariable analysis showed that non-black race, bone pain, SRE prior to radium, and higher PSA were all linked with worse mortality. 

 

Conclusions: We described the largest known cohort of men in the real world who received radium-223. We identified common treatment patterns with differing risk for overall mortality. Further prospective studies are needed to better understand whether differences in survival are attributed to worsening disease status requiring more aggressive therapy, lead-time bias, or true differences in treatment efficacy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Racial disparities in radium-223 treatment in a large real-world population.},

author = {Hanson Hanqing Zhao and Lauren Howard and Amanda Hoedt and Martha K Terris and Christopher L. Amling and Christopher J. Kane and Matthew R. Cooperberg and William J. Aronson and Thomas Polascik and Stephen J. Freedland},

doi = {https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.7_suppl.190},

year  = {2019},

date = {2019-02-01},

urldate = {2019-02-01},

journal = {Journal of Clinical Oncology},

volume = {37},

number = {7},

pages = {268},

abstract = { 

Background: Black men with prostate cancer are more likely to have unfavorable tumor characteristics and are at greater risk of prostate cancer mortality. Radium-223 is a FDA approved treatment for metastatic castration-resistant prostate cancer (mCRPC) that showed a survival benefit in the ALSYMPCA trial, where 94% of the participants were Caucasian. We aim to examine treatment patterns and outcomes of radium-223 in a large, heterogeneous population in the real world. 

 

Methods: We reviewed charts of all men with diagnosed with mCRPC in the entire Veterans Affairs (VA) system alive as of January 1st, 2013 who received radium-223. We compared common treatment patterns and characteristics between black and nonblack men. We analyzed predictors of time from radium-223 start to overall survival and time to skeletal related event (SRE) with Cox models. 

 Results: 318 patients with bone mCRPC who received radium-223 were identified. 27% (87/318) were black. Black men were younger (67 vs 70 years},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2018.02.694,

title = {MP21-03 SERUM LIPID PROFILE AT TIME OF ANDROGEN DEPRIVATION THERAPY AND RISK OF CASTRATION-RESISTANT PROSTATE CANCER: RESULTS FROM THE SEARCH DATABASE},

author = {Shweta Dambal and Lauren Howard and Emma Allott and William Aronson and Christopher Kane and Christopher Amling and Matthew Cooperberg and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2018.02.694},

doi = {https://doi.org/10.1016/j.juro.2018.02.694},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Urology},

volume = {199},

number = {4S},

pages = {e262-e263},

abstract = {INTRODUCTION AND OBJECTIVES

We previously showed that elevated serum triglycerides but not cholesterol, LDL or HDL in the year before radical prostatectomy (RP) were associated with increased risk of PSA recurrence. However, as cholesterol is the precursor for androgens and residual androgens are a key driver of castration-resistant prostate cancer (CRPC) after androgen deprivation therapy (ADT), we tested if lipid levels prior to ADT after RP were associated with CRPC risk. We hypothesized elevated cholesterol would increase CRPC risk.



METHODS

After excluding men who received statins prior to ADT, we identified 212 men in the SEARCH database with available serum lipid data within two years prior to ADT after RP. Lipids were treated as continuous and categorized as normal vs. abnormal (≥200 mg/dl for total cholesterol, ≥130 mg/dl for LDL, <40 mg/dl for HDL, ≥150 mg/dl for triglycerides). Cox models were used to test the association between lipids and CRPC risk after ADT. Models were adjusted for PSA at ADT, year of ADT, statin use after ADT as a time dependent covariate, and PSA doubling time at the time of ADT. In a subanalysis, we restricted models to men who never took statins even after ADT.



RESULTS

Median follow-up after ADT was 67 months (IQR 37-109) and 36 men developed CRPC. There were 148 (70%) men with cholesterol <200 and 64 (30%) with cholesterol ≥200 mg/dl. Men with elevated cholesterol had earlier years of surgery, longer follow-up, higher PSA at ADT, lower rate of post-RP radiation, higher rate of statin use after ADT, higher LDL, higher HDL, and higher triglycerides (all p≤0.01). Other disease characteristics were similar between groups. On multivariable analysis, there was no link between any lipid value and CRPC risk (all p>0.3). However, when restricting to men who never took a statin while on ADT, abnormal cholesterol was associated with increased CRPC risk on univariable analysis (HR 3.19, p=0.009). After adjustment, the association was attenuated and no longer significant, but the trend remained (HR 2.61, p=0.054).



CONCLUSIONS

Among men starting ADT who never took statins, high cholesterol was suggestively linked with increased CRPC risk. However, when including men who went on a statin after ADT, cholesterol was no longer linked with CRPC. This suggests that high cholesterol may be linked with CRPC and this excess risk is negated by statin use. Further studies are needed to confirm these findings and if confirmed, then to better understand the optimal timing of statin use to reduce CRPC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2018.02.717,

title = {MP22-06 SALVAGE RADIATION THERAPY FOR RECURRENT PROSTATE CANCER: CAN THE PROGNOSTIC GRADE GROUP SYSTEM INFORM TREATMENT TIMING?},

author = {Kae Jack Tay and Thomas Polascik and Lauren Howard and Joseph Salama and Ariel Schulman and Zinan Chen and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2018.02.717},

doi = {https://doi.org/10.1016/j.juro.2018.02.717},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Urology},

volume = {199},

number = {4S},

pages = {e273-e273},

abstract = {INTRODUCTION AND OBJECTIVES

Prior studies suggest for high-grade prostate cancer, earlier salvage radiotherapy (SRT) leads to improved PSA control, whereas for low-grade disease, PSA values up to 1 do not affect PSA control. We examined the association between pre-SRT PSA and PSA control as a function of the new prognostic grade group (GG) system.



METHODS

Using the SEARCH 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 hormonal therapy. Men were stratified by pre-SRT PSA (0.2-0.49, 0.5-0.99 and ≥1.0ng/ml). Multivariable Cox models were used to test the association between pre-SRT PSA and SRT failure, stratified by GG.



RESULTS

358 men met inclusion criteria and comprised our study cohort. Median post-SRT follow-up was 78 months. 174 (49%) men 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 GG 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 (HR = 2.29, p=0.001). Among GG 3-5, a PSA 0.5-0.99 ng/ml or ≥1.0 ng/mL had a higher recurrence risk (HR = 2.16, p=0.020 and HR = 2.02, p=0.035 respectively) versus PSA 0.2-0.49 ng/ml. The interaction between pre-SRT PSA and GG approached statistical significance (p=0.051).



CONCLUSIONS

Our results validate that in men with higher-grade prostate cancer (GG 3-5), SRT should be given earlier (PSA <0.5 ng/ml) while among men with lower-grade disease (GG 1-2), SRT results in equal PSA control up to PSA of 1.0 ng/ml.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2018.02.1103,

title = {MP34-11 OBESITY, RISK OF BIOCHEMICAL RECURRENCE, AND PSADT AFTER RADICAL PROSTATECTOMY: RESULTS FROM THE SEARCH DATABASE},

author = {Brandee Branche and Lauren Howard and Robert Hamilton and William Aronson and Martha Terris and Matthew Cooperberg and Christopher Amling and Christopher Kane and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2018.02.1103},

doi = {https://doi.org/10.1016/j.juro.2018.02.1103},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Urology},

volume = {199},

number = {4S},

pages = {e442-e442},

abstract = {INTRODUCTION AND OBJECTIVES

We previously showed that obesity is associated with increased risk of biochemical recurrence. More recently, we showed obesity is more strongly linked with increased risk of prostate cancer-specific mortality (PCSM) after radical prostatectomy, albeit based on small numbers of deaths. The fact that the link between obesity and PCSM was stronger than with recurrence suggests that either recurrences are more aggressive or obesity predicts poorer responses to salvage therapies such as hormonal therapy. To test the idea that more aggressive recurrences explain the stronger link with PCSM than with recurrence, we examined the association between body mass index (BMI) and aggressive recurrence, as measured by PSA doubling time (PSADT) using the Shared Equal Access Regional Cancer Hospital (SEARCH) database.



METHODS

We examined the association between BMI and biochemical recurrence among 4,123 men treated with radical prostatectomy between 1988 and 2016 within the SEARCH Database using a Cox model. Among men with a biochemical recurrence, PSADT was compared across BMI categories using linear regression. Models were adjusted for age, race, PSA, biopsy Gleason score, clinical stage, year, and surgical center.



RESULTS

Overall, 922 men (23%) were normal weight (BMI <25 kg/m2), 1863 (45%) were overweight (BMI 25-29.9 kg/m2), 968 (23%) were obese (BMI 30-34.9 kg/m2), and 370 (9%) were moderately or severely obese (BMI =35 kg/m2). After adjustment for multiple clinical characteristics, higher BMI was significantly associated with higher risk of biochemical recurrence (p=0.008). However, among men with a biochemical recurrence, 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=0.27).



CONCLUSIONS

We confirmed that men with higher BMI were more likely to have biochemical recurrence. However, we also found no link between BMI and PSADT at the time of recurrence. Given the known stronger association between obesity and increased risk of PCSM after radical prostatectomy versus recurrence in general, our data suggest that the strength of the association with PCSM is not due to more aggressive recurrences among obese men. Future studies are needed in regards to obesity and response to salvage therapies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2018.02.1644,

title = {MP51-13 THE IMPACT OF COMORBIDITY AND AGE ON TIMING OF ANDROGEN DEPRIVATION THERAPY IN MEN WITH BIOCHEMICAL RECURRENCE AFTER RADICAL PROSTATECTOMY},

author = {Ariel Moradzadeh and Lauren Howard and William Aronson and Martha Terris and Matthew Cooperberg and Christopher Amling and Christopher Kane and Stephen Freedland and Timothy Daskivich},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2018.02.1644},

doi = {https://doi.org/10.1016/j.juro.2018.02.1644},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Urology},

volume = {199},

number = {4S},

pages = {e690-e690},

abstract = {INTRODUCTION AND OBJECTIVES

Androgen deprivation therapy (ADT) is the standard of care for men with biochemical recurrence (BCR) following definitive treatment for prostate cancer. While ADT has been shown to induce significant PSA regression, it is associated with increased risk of morbidity. While there are no established criteria for timing of ADT, some argue ADT should be delayed in older and/or sicker men to avoid treatment-related morbidity. We determined the impact of comorbidity and age on timing of ADT after BCR in a cohort of men undergoing radical prostatectomy (RP).



METHODS

We analyzed 611 men with BCR after RP treated with ADT from the Shared Equal Access Regional Cancer Hospital (SEARCH) database, which includes men undergoing RP at 6 VA Medical Centers. We ascertained age at ADT (<60, 60-64, 65-69, 70-74, >75) and Deyo-Charlson comorbidity index (CCI) scores (0, 1, 2, 3+) using claims data within 12 months of BCR. Multivariable logistic regression was used to determine how these features varied between men on timing of ADT (early (PSA<2.5) or delayed (PSA≥2.5). All models were adjusted for tumor risk factors (clinical stage, surgical margins, PSA at BCR, and PSA doubling time at BCR).



RESULTS

In multivariable analysis, age was a strong predictor of delayed ADT, while comorbidity was only a weak predictor. Compared with men aged <60 years, those aged 65-69 (OR 2.7, 95% CI 1.4-5.2), 70-74 (OR 3.7, 95% CI 1.8-7.7), and >75 (OR 7.5, 95% CI 3.6-15.8) had significantly higher odds of delayed ADT (p<0.001). In contrast, compared with men with CCI scores of 0, those with CCI 1 (OR 0.8, 95% CI 0.4-1.6) and CCI 2 (OR 1.6, 95% CI 0.8-3.2) did not have significantly increased odds of delayed ADT, while those with CCI 3+ (OR 1.9, 95% CI 1.1-3.3) had mildly increased odds (p=0.01). When treating PSA at ADT as a continuous variable, similar results were seen in multivariable linear regression. Results persisted in subgroups of men who received salvage radiation therapy and those who did not.



CONCLUSIONS

Among men with BCR after RP, age was more consistently and linearly associated with delayed ADT than comorbidity, which was only associated with delayed ADT in a subset of the sickest patients. Given the potentially life-threatening side effects of ADT in men with poor health status, comorbidity should play a more prominent role in triaging early vs. delayed ADT in men with BCR after RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2018.02.2907,

title = {MP87-07 STATIN USE IS ASSOCIATED WITH IMPROVED PROSTATE CANCER-SPECIFIC OUTCOMES IN WHITE BUT NOT BLACK MEN INITIATING ANDROGEN DEPRIVATION THERAPY},

author = {Emma Allott and Lauren Howard and William Aronson and Martha Terris and Christopher Kane and Christopher Amling and Matthew Cooperberg and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2018.02.2907},

doi = {https://doi.org/10.1016/j.juro.2018.02.2907},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Urology},

volume = {199},

number = {4S},

pages = {e1189-e1190},

abstract = {INTRODUCTION AND OBJECTIVES

Statins have been linked with lower risk of advanced prostate cancer (PC), reduced risk of recurrence and decreased PC-specific mortality. However, most studies were conducted in white men, and very few examined the effect of statin use on outcomes after androgen deprivation therapy (ADT). We examined the association between statin use and PC-specific outcomes in men initiating ADT in the minority-enriched SEARCH database, overall and stratified by race.



METHODS

We identified 570 PC patients (42% black) initiating ADT for disease recurrence after radical prostatectomy in SEARCH. Statin use prior to ADT, metastasis, castrate-resistant PC (CRPC), PC-specific mortality (PCSM) and all-cause mortality (ACM) data were abstracted from electronic medical records. We used Cox proportional hazards analysis to examine associations between statin use prior to ADT and risk of metastasis, CRPC, PCSM and ACM, adjusting for demographic, clinical and pathologic characteristics, overall and stratified by race.



RESULTS

Of 570 men, 308 (54%) were statin users prior to ADT initiation. Median follow-up among men who did not experience any event was 60 months (IQR 34-112). Statin users were older at ADT (65 vs. 63; p=0.004) and had a higher body mass index (p<0.001), but pathologic tumor characteristics did not vary significantly by statin use (all p>0.08). Overall, statin use was not associated with risk of metastasis, CRPC, PCSM, or ACM on either univariable or multivariable analysis (all p>0.2). However, univariable analysis in white men revealed significant inverse associations between statin use and risk of metastasis (HR 0.57; p=0.037), CRPC (HR 0.58; p=0.048) and PCSM (HR 0.46; p=0.04), with no significant associations in black men (p-interaction=0.008, 0.019, and 0.075, respectively). Adjusting for pathologic characteristics did not affect the direction or magnitude of these findings but reduced our power to detect significant associations.



CONCLUSIONS

We found statin use was associated with improved outcomes in PC patients undergoing ADT, but only among white men. Future research is needed to validate these findings and to explore biologic and non-biologic mechanisms that may contribute to the role of cholesterol and statins in PC as well as racial differences in these associations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2018.02.616,

title = {PD10-06 THE IMPACT OF PRIOR LOCAL THERAPY ON OVERALL SURVIVAL IN MEN WITH METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: RESULTS FROM SEARCH},

author = {Devin Patel and Shalini Jha and Lauren Howard and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Brian Chapin and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2018.02.616},

doi = {https://doi.org/10.1016/j.juro.2018.02.616},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Urology},

volume = {199},

number = {4S},

pages = {e229-e230},

abstract = {INTRODUCTION AND OBJECTIVES

In recent years, there has been growing interest in the role of prior local therapy on the outcomes of men with metastatic prostate cancer. Previous work showing this potential benefit of local therapy has not included men with metastatic castration-resistant prostate cancer (mCRPC). Our objective was to study the impact of previous local treatment with radical prostatectomy (RP) ± radiation (XRT) or XRT alone on overall survival (OS) and prostate cancer-specific survival (CSS) in men with newly diagnosed mCRPC.



METHODS

We performed a retrospective study of patients newly diagnosed with mCRPC 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 the 729 patients with mCRPC, 284 (39%) underwent no local treatment, 176 (24%) underwent RP ± XRT and 269 (37%) underwent XRT alone. On multivariable analysis, men with prior RP ± XRT had improved OS (HR, 0.71; p=0.005) and CSS (HR, 0.55; p<0.001) compared to men with no prior local therapy. This decreased risk of OS (HR, 0.89; p=0.219) and CSS (HR, 0.87; p=0.170) was not seen in men with prior XRT alone. After further adjusting for comorbidity with Charlson Comorbidity Index, patients with prior local therapy with RP ± XRT still had reduced OS (HR, 0.70; p=0.003) while this was not seen in patients who received prior XRT alone (HR, 0.88, p=0.185).



CONCLUSIONS

Independent of patient and disease related factors, including comorbidity, men with mCRPC who had undergone prior RP had improved OS and CSS when compared to men with no prior local therapy. The finding of improved survival in men newly diagnosed with mCRPC who had undergone prior RP is consistent with previous reports in men newly diagnosed with metastatic castration-sensitive disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2018.02.796,

title = {PD14-10 VALIDITY OF THE NATIONAL DEATH INDEX TO ACCURATELY CODE THE DATE OF DEATH AND DEATHS FROM PROSTATE CANCER, IN MEN HAVING UNDERGONE PROSTATECTOMY},

author = {Drew Moghanaki and Lauren Howard and Amanda De Hoedt and William Aronson and Christopher Kane and Christopher Amling and Matthew Cooperberg and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2018.02.796},

doi = {https://doi.org/10.1016/j.juro.2018.02.796},

year  = {2018},

date = {2018-01-01},

journal = {Journal of Urology},

volume = {199},

number = {4S},

pages = {e308-e309},

abstract = {INTRODUCTION AND OBJECTIVES

Concerns exist with the National Death Index (NDI) to accurately code the date and cause of death in men with prostate cancer. Meanwhile, datasets that entail a manual review of entire medical records provide more accurate assessments. This includes the SEARCH database which maintains records on over 5,000 prostatectomy patients whose electronic records are available within the Veterans Affairs (VA) healthcare system.



METHODS

The SEARCH database was queried for vital status up through 2012. Causes for death were coded as "prostate cancer" (PC) whenever there was progressive metastatic PC following hormonal therapy without another obvious cause of death, "other" whenever PC could be ruled out, and "unknown" whenever information was incomplete. The cause of death in the NDI was queried based on ICD-9 codes.



RESULTS

Vital status, death date, and cause of death for subjects in SEARCH were reconciled with the NDI. There were 1,327 and 1,093 patients coded as deceased in SEARCH and NDI, respectively. All deceased patients in the NDI were coded as dead in SEARCH, while 219 deaths in SEARCH were listed alive in the NDI, of which 164 were prior to 1998 (see Figure). For patients with concordant death status, 94% had an exact match for death date, 97% within one day, 99% within a week, and 100% within 31 days. NDI and SEARCH were concordant on 644 deaths from other causes and 92 PC deaths. Of the 104 patients coded in SEARCH as dead from PC, the NDI coded 77% accurately, with 11% as non-PC, and 12% as alive. Of the 139 patients coded in the NDI as dead from PC, SEARCH confirmed 66% to be accurate, with 34% as non-PC, and 0% as alive. Dropping patients with an unknown cause of death in either source, the positive predictive value for PC death in NDI was 72% and negative predictive value was 98%.



CONCLUSIONS

The NDI provides an accurate assessment of vital status, particularly after the late 1990's. It provides robust information on the date of death, when vital status is captured accurately. NDI had reasonable concordance with a high negative predictive value for PC death. However, a third of patients coded in the NDI as having died from PC actually died from other causes. This may reflect biased assignment on death certificates for decedents who have a prior history of PC and/or who have undergone a prostatectomy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.634,

title = {MP20-02 NOVEL RISK STRATIFICATION GROUPING USING STANDARD CLINICAL AND BIOPSY INFORMATION FOR PATIENTS UNDERGOING RADICAL PROSTATECTOMY: RESULTS FROM SEARCH},

author = {Zachary Zumsteg and Zinan Chen and Lauren Howard and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Daniel Spratt and Howard Sandler and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.634},

doi = {https://doi.org/10.1016/j.juro.2017.02.634},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e239-e239},

abstract = {INTRODUCTION AND OBJECTIVES

Prostate cancer is a heterogeneous disease, and risk stratification systems have been proposed to guide treatment decisions and inform patient prognosis. However, significant heterogeneity remains, especially among those with high risk disease, and thus improved stratification is needed.



METHODS

Data on 3335 men, including 605 high risk, undergoing radical prostatectomy without adjuvant treatment were collected in the SEARCH database. Patients were grouped into five categories: low risk (biopsy Gleason 2-6, T1a-T2a, and PSA <10ng/ml), favorable intermediate risk (FIR), unfavorable intermediate risk (UIR), standard high risk (SHR), very high risk (VHR). Intermediate risk patients by NCCN guidelines (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml) were UIR if they had biopsy Gleason 4+3, ≥50% positive biopsy cores, or multiple intermediate-risk factors (T2b or T2c, biopsy Gleason 7, or PSA 10-20ng/ml), and FIR otherwise. High risk patients by NCCN guidelines (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml) were VHR if they had primary Gleason 5, >50% positive biopsy cores, T3b-T4 or multiple high-risk factors (biopsy Gleason score 8-10, T3-T4, or PSA ≥20ng/ml), and SHR otherwise. Cox models were used to test the association between risk group and time to biochemical recurrence (BCR) and distant metastases (DM). Competing risks was used to test the association between risk group and prostate cancer-specific mortality (PCSM). Models were adjusted for age, race, year, and surgical center.



RESULTS

Median follow-up was 78 mo. Men with VHR disease had increased risk of BCR (p<0.001), DM (P=0.004), and PCSM (P=0.011) in comparison to SHR, but there were no differences in BCR, DM, or PCSM between SHR and UIR patients (p>0.4). FIR men had increased risk of BCR (HR 1.34, p=0.006) and DM (HR 2.42, p=0.035) compared to low risk men, but there was no difference in PCSM (p=0.17). Therefore, we propose a novel risk grouping: Group 1 (low risk), Group 2 (FIR), Group 3 (UIR and SHR), and Group 4 (VHR). These groups have markedly different outcomes, with 10 year DM rates of 0.7%, 2.8%, 6.9%, and 16.3% (p<0.001) for Groups 1-4 respectively, and 10 year PCSM of 0.3%, 1.9%, 3.3%, and 10.9% (P<0.001). The c-index of this grouping was 0.80 for DM vs. 0.76 for D'Amico risk groups.



CONCLUSIONS

Patients classified as VHR have 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{doi:10.1016/j.juro.2017.02.651,

title = {MP20-19 WHAT ARE THE BEST CUT-POINTS FOR PSA DOUBLING TIME IN MEN WITH NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER?},

author = {Lauren Howard and Daniel Moreira and Amanda De Hoedt and William Aronson and Christopher Kane and Christopher Amling and Matthew Cooperberg and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.651},

doi = {https://doi.org/10.1016/j.juro.2017.02.651},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e246-e247},

abstract = {INTRODUCTION AND OBJECTIVES

Prostate-specific antigen doubling time (PSADT) is a useful marker for assessing disease aggressiveness at multiple stages of prostate cancer. However, in men with non-metastatic castration resistant prostate cancer (M0 CRPC), there are no commonly used PSADT cut-points for risk stratification. We examined whether PSADT correlates with metastases, all-cause mortality (ACM), and prostate cancer-specific mortality (PCSM) and identified PSADT cut-points that can be used clinically for risk stratification in men with M0 CRPC.



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 development of metastasis, ACM, and PCSM. To identify cut-points, we categorized PSADT into groups of every 3 months (<3, 3-5.9, 6-8.9, 9-11.9, 12-14.9, 15-17.9, 18-20.9, 21-23.9, 24-119.9, 120) and then combined groups with similar hazard ratios. We tested the association between PSADT cut-points and each outcome using Cox models and compared survival using Kaplan-Meier estimates.



RESULTS

Median age was 77 months (IQR: 70-83) and 160 (36%) men were black. Median PSADT was 13.3 months (IQR: 6.4-94.3) and median follow-up was 28.3 months (IQR: 14.7-49.1). As a continuous variable, PSADT was associated with metastases, ACM, and PCSM (HR 1.40-1.68, all p<0.001). We identified the PSADT cut-points <3, 3-8.9, 9-14.9, ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM, and PCSM (all p<0.001). Men with a PSADT <3 months had a median 9 months to metastases, 16 months to PCSM, and 15 months to ACM. In contrast, men with a PSADT ≥15 months, had a median time to metastases of 50 months, 67 months to PCSM, and 46 months to ACM.



CONCLUSIONS

We found PSADT 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 are reasonable PSADT cut-points for risk stratification in men with M0 CRPC. These cut-points can be used for selecting high-risk men for clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.1469,

title = {MP47-09 TIMING OF PSA NADIR AFTER RADICAL PROSTATECTOMY AND RISK OF BIOCHEMICAL RECURRENCE: DOES IT MATTER? RESULTS FROM THE SEARCH DATABASE},

author = {Stephanie L Skove and Lauren E Howard and Jean-Alfred Thomas and William J Aronson and Martha K Terris and Matthew R Cooperberg and Christopher J Kane and Christopher L Amling and Daniel M Moreira and Stephen J Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.1469},

doi = {https://doi.org/10.1016/j.juro.2017.02.1469},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e631-e631},

abstract = {INTRODUCTION AND OBJECTIVES

Determining the risk of disease recurrence after radical prostatectomy (RP) is useful in early risk stratification. PSA nadir after RP is a strong predictor of biochemical recurrence (BCR). However, the time to nadir (TTN) has not been studied in the post-RP setting. We analyzed the association between PSA nadir level and TTN with BCR risk after RP among patients in the Shared Equal Access Research Cancer Hospital (SEARCH) Database.



METHODS

Using SEARCH, we identified men who either had an undetectable PSA (0 ng/ml) within 1-3 months after RP, or a detectable PSA within 1-3 months after RP and a follow-up PSA within 3-6 months after RP (n=1882). Men with a BCR or secondary treatment within 6 months of RP were excluded. Nadir was the lowest PSA within 1-6 months. We divided patients into 4 nadir groups: undetectable nadir and TTN 3-6 months (n=139), undetectable nadir and TTN 1-2.9 months (n=1290), detectable nadir and TTN 3-6 months (n=146), and detectable nadir and TTN 1-2.9 months (n=307). A Cox model was used to test the association between nadir group and risk of BCR. Time zero for all groups was 6 months after RP. The model was adjusted for race, BMI, age, year, surgical center, pre-RP PSA, Gleason score, and pathological features.



RESULTS

During a median follow-up of 65 months (IQR 29-111), 480/1882 (26%) men had a BCR. Among men with an undetectable PSA nadir and TTN 3-6 months, median time to first PSA was 1.6 months (IQR 1.3-2.1 months) after RP and median initial PSA was 0.02 (IQR 0.01-0.03). Among men with a detectable PSA at 1-3 months, 48% had a lower follow-up PSA 3-6 months after RP which was undetectable in 23% and lower but still detectable in 25%. Men with an undetectable PSA nadir and TTN 1-2.9 months had similar risk of BCR to men with an undetectable PSA nadir and TTN 3-6 months (HR 0.90, p=0.63). However, those with detectable nadir had increased risk of BCR (TTN 3-6 months: HR 2.01, p=0.009; TTN 1-2.99 months: HR 3.83, p<0.001), and those with shorter TTN (1-2.99 months) had higher risk of BCR than men with longer TTN (3-6 months) (p<0.001).



CONCLUSIONS

Among men undergoing RP with an undetectable PSA nadir, there was no association between TTN and risk of BCR. However, a shorter TTN was associated with an increased risk of BCR in men with detectable nadir. Intriguingly, nearly half of the men with a detectable PSA in first 3 months after RP had a lower follow-up PSA between 3 and 6 months after RP. This is contrary to common thinking that the first PSA after surgery is the nadir.



},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.214,

title = {PD03-08 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 = {Colette Whitney and Lauren Howard and Stephen Freedland and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Timothy Daskivich},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.214},

doi = {https://doi.org/10.1016/j.juro.2017.02.214},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e59-e60},

abstract = {INTRODUCTION AND OBJECTIVES

Given the protracted course of prostate cancer (PC) progression, competing risks of mortality is a key consideration in determining prognosis and treatment in all stages of the disease. We sought to examine the impact of age, Charlson Comorbidity Index (CCI), and PSA doubling time (PSADT) on all-cause mortality (ACM), prostate cancer-specific mortality (PCSM), and other-cause mortality (OCM) in a nationally representative sample of men with non-metastatic castration-resistant PC (M0/Mx CRPC).



METHODS

We analyzed 1,238 men diagnosed with M0/Mx CRPC in 2000 or later from 8 Veterans Affairs hospitals in the SEARCH database. CCI and PSADT were calculated at the time of M0/MX CRPC diagnosis, and cause of death was defined as PCSM or OCM. Men were divided into subgroups based on age (<70, 70-79, and ≥80), CCI (0, 1, 2, and 3+), and PSADT (<9 months, ≥9 months). Multivariable Cox proportional hazards analysis and competing risks regression analysis were used to determine the relative impact of age, CCI, and PSADT on ACM, PCSM, and OCM. Models were adjusted for race, year of diagnosis, site, biopsy Gleason score, PSA at CRPC, primary treatment, months from androgen deprivation to CRPC, and PSA velocity.



RESULTS

Men in our sample were generally older (<70, n=344; 70-79, n=418; ≥80, n=476), and the majority had CCI ≥2 (n=701). Competing risk regression analysis revealed that the risk of PCSM was appreciable for all subgroups, particularly among those with PSADT<9mos. However, the hazard of OCM was substantially higher for older, sicker men with high PSADT (Figure 1). For example, among men aged ≥80, those with CCI ≥3 and PSADT≥9 mos, cumulative incidence of PCSM/OCM at 5 years was 20%/50% compared with 30%/19% for CCI 0 and PSADT<9mos. Multivariable analysis showed that higher comorbidity burden predicted higher hazard of OCM across all ages; among those with CCI ≥3 (vs. 0), hazard ratios for OCM were 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 <70, 70-79, and ≥80, respectively.



CONCLUSIONS

Among men with M0/Mx CRPC, age, comorbidity, and PSADT are predictive of cause of death. Understanding the competing risks of PCSM and OCM is a critical consideration when counseling patients regarding prognosis and treatment of advanced PC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.216,

title = {PD03-10 VALIDATION OF THE 2015 PROSTATE CANCER PROGNOSTIC GRADE GROUPS FOR PREDICTING LONG-TERM ONCOLOGIC OUTCOMES IN A SHARED EQUAL ACCESS HEALTH SYSTEM.},

author = {Ariel Schulman and Lauren Howard and Kae Jack Tay and Rajan Gupta and Efrat Tsivian and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Stephen Freedland and Thomas Polascik},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.216},

doi = {https://doi.org/10.1016/j.juro.2017.02.216},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e60-e61},

abstract = {INTRODUCTION AND OBJECTIVES

The 2015 prostate cancer grading system was introduced to simplify pathologic stratification. We examine the performance of the Prognostic Grade Groups (PGG) in the Shared Equal Access Regional Cancer Hospital (SEARCH) database with respect to long term prostate cancer outcomes and whether associations vary by race within an equal access healthcare system.



METHODS

We performed a retrospective review of men undergoing radical prostatectomy at one of six Veterans Affairs hospitals between 1988 and 2015. We identified 4,325 men with available data. The prognostic ability of PGG for multiple long term clinical endpoints was examined using Cox models. Interactions between PGG and race were tested.



RESULTS

The cohort consisted of PGG 1 through 5, respectively: 2,077(48%), 1,171(27%), 521(12%), 409(10%), 147(3%). 1,596(38%) were African American. Median follow up was 86(IQR: 45 to 135) months. Higher PGG was associated with higher stage, older age, more recent year of surgery and surgical center (p<0.02). African American men had a lower PGG distribution (p=0.028). Higher PGG was associated with increased risk of all clinical endpoints on univariable and multivariable regression including biochemical recurrence (BCR), adjuvant therapy, castrate resistant prostate cancer (CRPC) [Figure 1, left], metastases, prostate cancer specific mortality (PCSM) and overall survival (OS) [Figure 1, right] (all p<0.001).We found no significant interactions with race in predicting any of the measured outcomes. (BCR: p=0.78, adjuvant therapy: p=0.60, CRPC: p=0.91, metastases: p=0.61, PCSM: p=0.83, OS: p=0.21).



CONCLUSIONS

The 2015 Prognostic Grade Groups predicted multiple long term clinical endpoints after prostatectomy in a large, multiracial cohort of men. The predictive value for survival endpoints was similar in Caucasian and African American men.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.574,

title = {PD10-11 ANALYSIS OF THE PREDICTIVE UTILITY OF PROGNOSTIC GRADE GROUPS (PGG) FOR PREDICTING PERIOPERATIVE ONCOLOGIC OUTCOMES OF RADICAL PROSTATECTOMY IN THE SHARED EQUAL ACCESS REGIONAL CANCER HOSPITAL (SEARCH) DATABASE},

author = {Ariel Schulman and Lauren Howard and Kae Jack Tay and Rajan Gupta and Efrat Tsivian and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Stephen Freedland and Thomas Polascik},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.574},

doi = {https://doi.org/10.1016/j.juro.2017.02.574},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e204-e204},

abstract = {INTRODUCTION AND OBJECTIVES

In 2015, Prognostic Grade Groups (PGG) 1 through 5 were introduced to reclassify Gleason pathology reporting. We studied the performance of the Prognostic Grade Groups (PGG) in the Shared Equal Access Regional Cancer Hospital (SEARCH) database for predicting perioperative oncologic outcomes within a multiracial equal access healthcare system.



METHODS

We reviewed records of men who underwent radical prostatectomy at one of six Veterans Affairs hospitals between 1988 and 2015. 4,200 men with available data were included. The predictive utility of biopsy PGG for multiple perioperative clinical endpoints was examined using logistic regression models. Interactions between PGG and race were tested.



RESULTS

The cohort consisted of PGG 1 through 5, respectively: 1,989(47%), 1,142(27%), 515(12%), 402(10%), 152(4%). 1,569(38%) were African American(AA). Higher biopsy PGG was associated with higher stage, older age, higher preoperative PSA and more positive biopsy cores (p≤0.012). Higher PGG was associated with higher risk of extracapsular extension(ECE), seminal vesicle invasion(SVI), positive surgical margins(PSM) and lymph node involvement(LNI) and lower likelihood of achieving PSA nadir <0.01 after surgery (all p<0.001). Lower PGG was more likely to be upgraded at surgery (p=<0.001). [Table 1 outlines risks associated with each PGG group.] AA men had decreased risk of upgrading (p=0.001). None of the other endpoints varied by race(p>0.1).



CONCLUSIONS

Prostate Prognostic Grade Groups predicted multiple perioperative oncologic endpoints after prostatectomy in a large, multiracial cohort of men. In this cohort, African American men had lower rates of pathologic upgrading at surgery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.1086,

title = {PD24-09 IN MEN WITH CASTRATION-RESISTANT PROSTATE CANCER VISCERAL METASTASES PREDICTS SHORTER OVERALL SURVIVAL: WHAT PREDICTS VISCERAL METASTASES? RESULTS FROM THE SEARCH DATABASE},

author = {Colette Whitney and Lauren Howard and Edwin Posadas and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.1086},

doi = {https://doi.org/10.1016/j.juro.2017.02.1086},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e455-e455},

abstract = {INTRODUCTION AND OBJECTIVES

Although visceral metastases (VM) are widely recognized to portend worse prognoses compared to bone and lymph metastases in prostate cancer, currently little is known about what predicts VM and the extent to which men with VM do worse, particularly at the time of initial diagnosis of metastatic castration-resistant prostate cancer (mCRPC). Our study aimed to determine whether men with VM at initial mCRPC diagnosis have worse overall survival and identify predictors of VM.



METHODS

We analyzed 494 men diagnosed with CRPC post-1999 and no known metastases from five Veterans Affairs hospitals of the SEARCH database who later developed metastases. Radiology scans (bone scan, MRI, CT scan, X-ray) within 30 days of initial metastasis diagnosis were reviewed to collect information on bone, visceral, and lymph node metastases. We analyzed the 236 men who had a CT scan performed. Predictors of VM and overall survival were evaluated using logistic regression and Cox models, respectively. Variables included age, year, race, treatment center, biopsy Gleason, primary localized treatment, metastases in lymph nodes, PSA, PSA doubling time, time from androgen deprivation therapy to CRPC, and time from CRPC to metastases.



RESULTS

Of the 236 mCRPC patients, 38 (16%) had VM. Regarding VM, 19 (50%), 8 (21%), and 16 (42%) patients had metastases in the liver, lungs, and other locations, respectively. VM was a predictor of overall survival on crude analysis (HR=1.88, 95% 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, PSA, and time from CRPC to metastases were significant in predicting overall survival (all p<0.05). None of the variables tested were associated with having VM (all p>0.09).



CONCLUSIONS

Neither demographic, tumor, nor PSA-kinetic characteristics were predictive of having VM, but VM predicted worse overall survival. There are currently no known clinical predictors of VM; however, since patients with VM have worse overall survival, there remains a need for further research to determine what predicts VM. Efforts targeted at identifying novel biomarkers for VM have the potential to have the greatest impact for those suffering from this particular disease state.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.1747,

title = {PD40-07 DOES EARLY PSADT (EPSADT) AFTER RADICAL PROSTATECTOMY, CALCULATED PRIOR TO PSA RECURRENCE, CORRELATE WITH PROSTATE CANCER (PC) OUTCOMES? RESULTS FROM THE SEARCH DATABASE},

author = {Anna Teeter and Kagan Griffin and Lauren Howard and William Aronson and Martha Terris and Christopher Kane and Christopher Amling and Matthew Cooperberg and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.1747},

doi = {https://doi.org/10.1016/j.juro.2017.02.1747},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e752-e752},

abstract = {INTRODUCTION AND OBJECTIVES

A short PSA doubling time (PSADT), calculated using PSA values ≥0.2 ng/ml, after biochemical recurrence (BCR) post radical prostatectomy (RP) portends a poor prognosis. We tested if ePSADT, calculated from the first detectable PSA after RP and including all values up to and including the first BCR value, predicts castration-resistant PC (CRPC), metastases, all-cause mortality (ACM) and PC-specific mortality (PCSM).



METHODS

Cox proportional hazards were used to test the association between ePSADT and CRPC, metastases, ACM, and PCSM in 674 men in the SEARCH database who underwent RP between 1988-2015 and later recurred. Men had to have at least 2 PSA values separated by at least 3 months to calculate ePSADT. Men who started salvage therapy within this time were censored and did not have ePSADT calculated. Thus, all PSA values used were prior to subsequent therapy. ePSADT was examined as a log-transformed continuous and categorical variable.



RESULTS

During a median 69-month follow-up (IQR 35-117) after BCR, 43 developed CRPC, 59 metastases, 236 all-cause deaths, and 30 PC-specific deaths. After adjusting for multiple clinicopathological variables, log-transformed ePSADT was not associated with any outcome. However, when ePSADT was categorized as ≥15, 9-14.9, 3-8.9, and <3 months, those with ePSADT <3 months were at increased risk of CRPC (HR 6.20, p=0.004), metastases (HR 5.26, p=0.002), PCSM (HR 5.06, p=0.017), and ACM (HR 1.63, p=0.070) vs. ePSADT ≥15 months, though the association with ACM was not significant. Similarly, ePSADT 3-9 months increased risk of CRPC (HR 3.56, p=0.015), metastases (HR 1.92, p=0.13), PCSM (HR 3.17, p=0.044), and ACM (HR 1.67, p=0.006) vs. ePSADT ≥15 months, though the association with metastases was not significant. See figure for CRPC risk by ePSADT.



CONCLUSIONS

Shorter ePSADT, particularly ePSADT <9 months, calculated using PSA values before and up to BCR, is associated with increased risk of CRPC, metastases, PCSM, and ACM among men with BCR after RP. ePSADT allows for risk-stratification at the time of BCR and before PSADT is calculable allowing these men to receive early aggressive secondary treatment and/or be enrolled on clinical trials.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2017.02.1752,

title = {PD40-12 DO SICKER PEOPLE HAVE WORSE PROSTATE CANCER-SPECIFIC OUTCOMES AFTER RADICAL PROSTATECTOMY? RESULTS FROM SEARCH},

author = {Anna Teeter and Xizi Sun and Lauren Howard and William Aronson and Christopher Kane and Christopher Amling and Matthew Cooperberg and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2017.02.1752},

doi = {https://doi.org/10.1016/j.juro.2017.02.1752},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Urology},

volume = {197},

number = {4S},

pages = {e754-e754},

abstract = {INTRODUCTION AND OBJECTIVES

Previous studies showed that higher Charlson comorbidity index increased the risk of overall mortality after radical prostatectomy. However, the relationship between comorbidities and prostate cancer-specific outcomes is less well established. While Charlson comorbidity index is a good measurement of health status, it is difficult to capture in retrospective data. Thus, we tested whether a man's overall health status, as reflected by the ASA (American Society of Anesthesiology) score, at the time of radical prostatectomy was associated with more distant prostate cancer-specific outcomes, such as biochemical recurrence (BCR), metastasis, and prostate cancer-specific mortality (PCSM).



METHODS

Data were retrospectively collected on 3102 men who underwent RP between 1992 and 2015 at six Veterans Affairs hospitals in the SEARCH database. Cox proportional hazards analysis was used to test the association between ASA score and BCR, metastasis, all-cause mortality, and PCSM. Models were adjusted for age, race, year of surgery, surgical center, BMI, PSA, biopsy Gleason score, and clinical stage. As 98% of men had a ASA score of 2 or 3, we categorized ASA score as 1-2 vs. 3-4.



RESULTS

There were 1419 (46%) men with ASA score 1-2 and 1683 (54%) men with ASA score 3-4. Men with ASA score 3-4 were older (mean 62 vs. 61), had more recent year of surgery (median 2009 vs. 2007), higher BMI (median 28.6 vs. 27.8), and higher biopsy Gleason score, versus men with ASA score 1-2 (all p<0.001). Men in the higher ASA group had an increased risk of all-cause mortality compared to men in the lower ASA grouping (HR 1.59, p<0.001). There was no increased risk of BCR (p=0.23), metastasis (p=0.22), or PCSM (p=0.83).



CONCLUSIONS

We found that men who underwent radical prostatectomy for prostate cancer with worse baseline health, as reflected by a higher ASA score (3-4 vs. 1-2), had a higher risk of all-cause mortality but did not have higher risk of the adverse prostate-cancer specific outcomes of BCR, metastasis, or death from prostate cancer. Whether similar results would be obtained if a more granular measure of comorbidity had been used remains to be tested.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2016.02.2305,

title = {MP09-18 BIOPSY-DETECTED GLEASON PATTERN 5 IS A PARTICULARLY STRONG PREOPERATIVE PREDICTOR OF RECURRENCE, METASTASIS, AND MORTALITY IN MEN WITH HIGH-RISK PROSTATE CANCER},

author = {Sean Stroup and Daniel Moreira and Zinan Chen and Lauren Howard and Martha Terris and William Aronson and Matthew Cooperberg and Christopher Amling and Christopher Kane and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2016.02.2305},

doi = {https://doi.org/10.1016/j.juro.2016.02.2305},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Urology},

volume = {195},

number = {4S},

pages = {e100-e101},

abstract = {INTRODUCTION AND OBJECTIVES

We sought to evaluate the relative risk of biochemical recurrence and risk of death from prostate cancer contributed by biopsy Gleason pattern 5 among high-risk men with Gleason 8 - 10 disease in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.



METHODS

Men with biopsy Gleason sum 8 - 10 prostate cancer treated with radical prostatectomy were evaluated. The cohort was divided: Gleason 4+4 vs. those with any pattern 5 (i.e., Gleason 3+5, 4+5, 5+3, 5+4, and 5+5). Biochemical recurrence was defined as PSA >0.2ng/mL, 2 values at 0.2ng/mL, or secondary treatment for an elevated PSA. Predictors of PSA recurrence, metastasis free survival, prostate cancer specific survival, and overall survival were analyzed using Kaplan-Meier, log-rank test and Cox proportional hazards model.



RESULTS

We identified 633 high-risk men in the SEARCH database who met criteria for inclusion. Of these, 394 (62%) had Gleason 4+4, and 239 (38%) had Gleason pattern 5 on biopsy. Baseline characteristics were not significantly different between groups aside from year of surgery in Gleason 4+4 vs. any Gleason 5, respectively (median 2008 vs. 2010, p = 0.017). On multivariable analysis, relative to Gleason 4+4, high-risk men with Gleason pattern 5 had a no differences in the risk of biochemical recurrence (HR=1.23; 95%CI=0.97-1.57; P=0.092), but a significantly greater risk of developing metastasis (HR=1.93; 95%CI=1.08-3.45, p=0.026), and a significantly greater risk of prostate cancer specific mortality (HR=2.01; 95%CI=1.02-3.94; p=0.043) and overall mortality (HR=1.41; 95%CI=0.99-2.00; p=0.056) (Figure 1).



CONCLUSIONS

Among men with high-risk prostate cancer identified by biopsy Gleason grading, those with any Gleason pattern 5 vs. 4+4 are at the highest risk of progression. Presence of any Gleason 5 on biopsy is associated with a two-fold greater risk of metastasis and death from prostate cancer and negatively impacts overall survival.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2016.02.447,

title = {MP50-13 VALIDATION OF A BONE SCAN POSITIVITY RISK TABLE IN NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER},

author = {Daniel Moreira and Lauren Howard and Brian Hanyok and Vishnu Kadiyala and Jameson Kuang and Colette Whitney and Floyd Wilks and Christopher Kane and Martha Terris and Christopher Amling and Matthew Cooperberg and William Aronson and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2016.02.447},

doi = {https://doi.org/10.1016/j.juro.2016.02.447},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Urology},

volume = {195},

number = {4S},

pages = {e677-e677},

abstract = {INTRODUCTION AND OBJECTIVES

The most common means to detect prostate cancer metastases remain a bone scan. However, most bone scans are negative. Previously, we developed a table to predict the risk of a positive bone scan based upon prostate-specific antigen (PSA) and PSA doubling time (PSADT) at the time of bone scan imaging. Herein, we tested the external validity of this table to predict bone scan positivity using data from a separate cohort of men diagnosed with M0/Mx castrate-resistant prostate cancer (CRPC) within the VA system.



METHODS

We retrospectively analyzed 429 bone scans of 281 CRPC patients with no known prior 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 prior 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 PSA (HR 2.13, 95%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 <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.



CONCLUSIONS

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{doi:10.1016/j.juro.2016.02.2013,

title = {MP79-15 RADICAL PROSTATECTOMY AND THE EFFECT OF CLOSE SURGICAL MARGINS: ANALYSIS FROM THE SEARCH DATABASE},

author = {Sean Stroup and Zinan Chen and Lauren Howard and Stephen Freedland and Daniel Moreira and Martha Terris and William Aronson and Matthew Cooperberg and Christopher Amling and Christopher Kane},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2016.02.2013},

doi = {https://doi.org/10.1016/j.juro.2016.02.2013},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Urology},

volume = {195},

number = {4S},

pages = {e1040-e1040},

abstract = {INTRODUCTION AND OBJECTIVES

Positive surgical margins after radical prostatectomy are a significant predictor for biochemical failure. Close surgical margins however represent a diagnostic challenge for surgeons. We sought to evaluate the biochemical recurrence patterns among men with radical prostatectomy specimens having negative, positive, and close surgical margins from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.



METHODS

Men undergoing radical prostatectomy between 1988 and 2015 with known final pathologic margin status were evaluated. The cohort was divided into 3 groups based on margin status; negative, positive, and close. Close margins were defined by distance of tumor ≤1mm from the surgical margin or by pathologic description from reports. Biochemical recurrence was defined as PSA >0.2ng/ml, 2 values at 0.2ng/ml, or secondary treatment for an elevated PSA. Predictors of PSA recurrence and prostate cancer specific death were analyzed using Cox-proportional hazard models.



RESULTS

Of 5,416 men in the SEARCH database, 4,224 (78%) men met criteria for inclusion in the analysis. Of these, 2,016 (48%) had negative margins, 1,851 (44%) had positive margins, and 357 (8%) had close margins. On multivariable analysis, relative to negative margins, men with close margins had a higher risk of biochemical recurrence (HR=1.57, 95%CI=1.41-2.10, P<0.001). However, this risk was lower than that or men with a positive margin (HR=2.16, 95%CI=1.91-2.44, P<0.001). However, both close (p=0.25) and positive margins (p=0.95) were unrelated to disease-specific survival.



CONCLUSIONS

Close but negative margins are associated with an intermediate risk of BCR - greater than negative margins, but less than men with positive margins. However, consistent with prior studies from our group, all margin categories were unrelated to disease-specific survival. Close or positive margins, in the absence of other high-risk features, do not increase the risk of death and should not be used alone to make adjuvant therapy decisions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2016.02.392,

title = {PD28-05 FACTORS PREDICTING SKELETAL-RELATED EVENTS IN PATIENTS WITH BONE METASTATIC CASTRATION-RESISTANT PROSTATE CANCER},

author = {Zachary Klaassen and Lauren Howard and Amanda de Hoedt and Christopher L Amling and William J Aronson and Matthew R Cooperberg and Christopher J Kane and Martha K Terris and Stephen J Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2016.02.392},

doi = {https://doi.org/10.1016/j.juro.2016.02.392},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Urology},

volume = {195},

number = {4S},

pages = {e656-e656},

abstract = {INTRODUCTION AND OBJECTIVES

Bone metastases frequently cause skeletal related events (SRE) in patients with metastatic castration-resistant prostate cancer (CRPC). However, there is a paucity of data identifying which factors are associated with SRE for patients with bone metastatic CRPC (mCRPC). Thus, the objective of this study was to assess predictors of SRE using characteristics commonly available in the medical chart at the time of bone mCRPC diagnosis.



METHODS

Data from 459 patients diagnosed with non-metastatic CRPC from 2000-2013 were identified from the San Diego, CA and Durham, NC Veteran Affairs Medical Centers. Among these men, 233 (51%) developed bone metastases during follow-up and were included in the study cohort. First occurrence of an SRE (pathologic fracture, spinal cord compression, radiation to bone, or surgery to bone) was abstracted from the medical records. The potential predictors for SRE included age, year of mCRPC diagnosis, race, treatment center, biopsy Gleason score, primary localized treatment, PSA at metastasis, PSA doubling time (PSADT), months from androgen deprivation therapy to CRPC, months from CRPC to metastasis, number of bone metastases, and bone pain. Univariable hazard ratios (HR) were estimated for each predictor using Cox proportional hazards, and forward selection with alpha=0.2 was used to select the strongest predictors of time to SRE. The area under the curve (AUC) of the final multivariable model was calculated to assess its accuracy.



RESULTS

The median age at diagnosis of bone mCRPC was 75 years (IQR: 68-81), and there were 80 (34%) black patients and 153 (66%) non-black patients. During follow-up (median 11.2 months, IQR: 4.9-22.1 months), 88 patients (38%) had a SRE. On univariable analysis, earlier year of metastasis (HR 0.91, p=0.005), PSADT ≥9 vs. <9 months (HR 0.50, p=0.011), and bone pain (HR 3.34, p<0.001) were all associated with increased SRE risk. Among men with vs. without bone pain, 54% vs. 28% developed an SRE. On multivariable analysis, earlier year of metastasis (HR 0.93, p=0.028), biopsy Gleason score of 7 vs. ≤6 (HR 1.74, p=0.041), radiation as primary localized treatment vs. none (HR 2.33, p<0.001), and bone pain (HR 3.64, p<0.001) were associated with increased SRE risk. The AUC of this model was 0.744.



CONCLUSIONS

Bone pain was the strongest predictor of SRE in this study of men with bone mCRPC. Importantly, patients at high-risk of an SRE can be identified and these men should be treated with a bone-targeted agent to prevent SREs.



},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2016.02.1755,

title = {PD42-03 PATHOLOGIC AND BIOCHEMICAL OUTCOMES AMONG AFRICAN-AMERICAN AND CAUCASIAN MEN WITH LOW-RISK PROSTATE CANCER IN THE SEARCH DATABASE: IMPLICATIONS FOR ACTIVE SURVEILLANCE CANDIDACY},

author = {Michael Leapman and Stephen Freedland and William Aaronson and Christopher Kane and Martha Terris and Kelly Walker and Christopher Amling and Peter Carroll and Matthew Cooperberg},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2016.02.1755},

doi = {https://doi.org/10.1016/j.juro.2016.02.1755},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Urology},

volume = {195},

number = {4S},

pages = {e987-e988},

abstract = {INTRODUCTION AND OBJECTIVES

Racial disparities in the incidence and risk profile of prostate cancer (PCa) at diagnosis among African-American (AA) men are well reported, however it remains unclear whether AA race is independently associated with adverse pathological findings among men with clinical low risk disease.



METHODS

We conducted a retrospective analysis among 895 men with clinical low risk (Gleason 3+3, clinical stage ≤T2a, PSA≤10 ng/mL) PCa treated with radical prostatectomy within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. We evaluated baseline clinical and demographic characteristics stratified by AA or Caucasian race. Associations between AA versus Caucasian race with pathologic Gleason upgrade (≥3+4), major upgrade (≥4+3), upstage (pT3a or higher), positive margin status and biochemical recurrence were examined using chi-square, logistic regression, log-rank, and Cox proportional hazards analyses.



RESULTS

We identified 355 AA and 540 Caucasian men with low-risk tumors within the SEARCH cohort followed for a median of 6.3 years (IQR 3.8-8.9). AA men were younger (mean 59.5vs. 62.0 years, p<0.001), and had higher median PSA (5.5 vs. 5.1, p<0.001). Following adjustment for relevant covariates, AA race was not significantly associated with pathological upgrade (OR 1.34, 95% CI 0.94-1.91, p=0.111), major upgrade (OR 0.56, 95% CI 0.30-1.05, p=0.070), upstaging (OR 1.11, 95% CI 0.67-1.84, p=0.683), or positive surgical margins (OR 1.05, 95% CI 0.73-1.49, p=0.806). The 5-year recurrence-free survival rates were 73.4% and 78.4% for AA and Caucasian men, respectively (log-rank p=0.178). In a Cox proportional hazards analysis model, AA race was not significantly associated with BCR (HR 1.11, 95% CI 0.81-1.50, p=0.521).



CONCLUSIONS

In a cohort of low-risk men treated with prostatectomy within an equal access health system with a high representation of AA men, no significant differences were observed in the rates of pathologic upgrading, upstaging or biochemical recurrence. These data support continued use of AS in AA. Upgrading and upstaging remain concerning possibilities for all men regardless of race.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2016.02.1780,

title = {PD43-02 ARE WE OPERATING ON WHO WE SHOULD? THE CHANGING CHARACTERISTICS OF RADICAL PROSTATECTOMY PATIENTS: RESULTS FROM THE SHARED EQUAL ACCESS REGIONAL CANCER HOSPITAL (SEARCH) DATABASE},

author = {Kathleen McGinley and Lauren Howard and Zinan Chen and William Aronson and Martha Terris and Christopher Kane and Christopher Amling and Matthew Cooperberg and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2016.02.1780},

doi = {https://doi.org/10.1016/j.juro.2016.02.1780},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Urology},

volume = {195},

number = {4S},

pages = {e993-e993},

abstract = {INTRODUCTION AND OBJECTIVES

The overtreatment of low-risk prostate cancer has many adverse effects including creating harm for our patients and contributing to prostate cancer screening guidelines arguing the harms of screening outweigh the benefits. While a growing body of literature suggests increasing rates of active surveillance among men with low-risk prostate cancer, an understanding of the characteristics of men undergoing radical prostatectomy over time is lacking. We examined demographic and clinical characteristics of men undergoing radical prostatectomy in a multi-center equal access setting.



METHODS

We used the SEARCH database to identify men who had a radical prostatectomy from 1994-2015 with complete data. We compared median age, race, median PSA, clinical stage, biopsy Gleason score, and AUA risk category of men undergoing radical prostatectomy between 1994-1999, 2000-2005, 2006-2011, 2012-2013, and 2014-2015 using Kruskal-Wallis and chi-square tests.



RESULTS

4208 men met inclusion criteria: 611 from 1994-1999, 1238 from 2000-2005, 1512 from 2006-2011, 554 from 2012-2013, and 293 from 2014-2015. Over time, black men comprised a greater percentage of those undergoing radical prostatectomy (35% in 1994-1999 vs. 43% in 2014-2015; p<0.001). We identified downward migrations in median PSA values (7.9 ng/mL in 1994-1999 vs. 6.3 ng/mL in 2014-2015; p<0.001) and clinical stage (47% T1c in 1994-1999 vs. 67% in 2014-2015; p<0.001). Biopsy Gleason scores among men undergoing radical prostatectomy increased over time, with a marked transition in the past several years (70% biopsy Gleason 2-6 in 1994-1999 vs. 17% in 2014-2015; 8% biopsy Gleason 8-10 in 1994-1999 vs. 27% in 2014-2015; p<0.001). By AUA risk category, fewer men with low-risk disease (42% in 1994-1999 vs. 13% in 2014-2015) received a radical prostatectomy over time, while increasing numbers of men with intermediate- (34% in 1994-1999 vs. 54% in 2014-2015) and high-risk (24% in 1994-1999 vs. 33% in 2014-2015; p<0.001) disease received a radical prostatectomy.



CONCLUSIONS

Within our dataset, <15% of radical prostatectomies were performed for low-risk disease in the past 2 years. Indeed, radical prostatectomy is increasingly being performed in men with intermediate- and high-risk prostate cancer and uncommonly for men with low-risk disease. This finding suggests decreasing rates of surgical overtreatment of low-risk prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Utilization and impact of surgical technique on the performance of pelvic lymph node dissection at radical prostatectomy: Results from the SEARCH database.},

author = {Kathleen F. McGinley and Xizi Sun and Lauren E. Howard and William J. Aronson and Martha K. Terris and Christopher J. Kane and Christopher L. Amling and Matthew R. Cooperberg and Stephen J. Freedland},

doi = {https://ascopubs.org/doi/abs/10.1200/jco.2015.33.7_suppl.73},

year  = {2015},

date = {2015-03-01},

urldate = {2015-03-01},

journal = {Journal of Clinical Oncology},

volume = {33},

number = {7},

pages = {73},

abstract = {Background: Performance of a pelvic lymph node dissection (PLND) with radical prostatectomy (RP) is critical for staging and treatment of high-risk prostate cancer (PC). Conversely, performance of a PLND in low-risk PC contributes to morbidity with minimal benefit. Robot-assisted laparoscopic RP (RARP) is associated with decreased PLND use. We evaluated PLND use over time, stratified by PC risk group and surgical technique. 

 

Methods: We used SEARCH to identify men who had open RP (ORP) or RARP from 2006-2013 with complete data. Univariable logistic regression was used to test the association between age, race, BMI, number of positive cores, AUA risk group, year, center, and surgical technique on PLND use. Multivariable logistic analysis was used to examine surgical technique and PLND performance stratified by AUA risk-group. Spearman correlation was used to examine temporal changes in PLND utilization stratified by risk-group and surgical technique. 

 Results: 1,439 men met inclusion criteria. Of these, 66% had a PLND. On univariable analysis, age, year, number of positive cores, AUA risk group, center, and surgical technique were significantly associated with PLND performance (all p<0.02). On multivariable analysis, when adjusted for age, race, BMI, number of positive cores, year, and center, RARP was associated with a 89% decreased use of PLND in the low-risk group, 85% decreased in intermediate risk, and 86% decreased in high risk men (all p≤0.002). Over time, PLND was increasingly used with RARP in low-risk patients (p=0.022); a trend of increased PLND performance with RARP in high risk men was noted (p=0.077) reaching ~85% in 2012-2013 vs. ~95% in ORP. For ORP, PLND use did not significantly change over time except a trend of fewer PLND in low-risk men which decreased to ~35% (p=0.064) in 2012-2013. 

 

Conclusions: Regardless of risk group, PLND is markedly less likely to be performed when a RARP is done. While improved over time, PLND remains over-utilized in low-risk men and under-utilized in high risk men regardless of surgical technique.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.874,

title = {MP14-12 OBESE CASTRATION-RESISTANT PROSTATE CANCER PATIENTS MAY BE AT A LOWER RISK OF METASTASIS AND ALL-CAUSE MORTALITY: RESULTS FROM THE SEARCH DATABASE},

author = {Adriana C Vidal and Lauren E Howard and Christopher J Kane and Martha K Terris and William J Aronson and Matthew R Cooperberg and Christopher L Amling and Stephen J Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.874},

doi = {https://doi.org/10.1016/j.juro.2015.02.874},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e155-e155},

abstract = {INTRODUCTION AND OBJECTIVES: At a population level obesity is associated with prostate cancer mortality; however some studies also showed a higher BMI can be protective against worse long-term prostate cancer outcomes among men with metastatic castration-resistant prostate cancer (CRPC). We investigated the effect of obesity on prostate cancer progression to metastasis and all-cause mortality exclusively among non-metastatic CRPC patients.



METHODS: We analyzed data from 420 documented M0 CRPC patients from SEARCH regardless of primary treatment modality. Our exposure, body mass index (BMI) was calculated from height and weight abstracted from the medical records at the time of but prior to CRPC diagnosis and categorized as normal weight (<25 kg/m2), overweight (25–29.9kg/m2), and obese (≥30kg/m2). Cox models were used to test associations between obesity and progression to metastasis and all-cause mortality, accounting for age at CRPC, race, year of CRPC diagnosis, treatment center, primary prostate cancer treatment, biopsy Gleason score, and PSA at CRPC.



RESULTS: Overall, 99 (24%) men had normal weight, 161 (38%) were overweight, and 160 (38%) were obese. In both unadjusted and adjusted analyses, a higher BMI was significantly associated with reduced risk of metastasis (crude HR=0.97, p=0.024; adjusted HR=0.95, p<0.001) and all-cause mortality (crude HR=0.98, p=0.028; adjusted HR=0.97, p=0.014). Likewise, when BMI was treated as a categorical variable in adjusted models, obesity was statistically significantly associated with reduced risk of developing metastases (crude HR=0.57, p=0.002) and of all-cause mortality (HR=0.63, p=0.004) when compared to normal weight. In unadjusted models, obesity was associated with lower risk of all-cause mortality (HR=0.70, p=0.018), but not with metastases (HR=0.74, p=0.078).



CONCLUSIONS: Among exclusively M0 CRPC patients, obesity is protective against disease progression and overall survival. Whether these results reflect lower BMI is due to cancer cachexia and serves as surrogate of more aggressive disease or whether obesity is biological protective for prostate cancer progression in late-stage disease is unclear. However, if confirmed in other studies, these findings have clinical implications suggesting obesity is associated with slower disease progression and better survival in men with M0 CRPC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.160,

title = {MP4-17 PATHOLOGIC GLEASON 8-10: DO ALL MEN DO POORLY? RESULTS FROM THE SEARCH DATABASE},

author = {Sean Fischer and Ross Simon and Lauren Howard and William Aronson and Martha Terris and Christopher Kane and Christopher Amling and Matt Cooperberg and Stephen Freedland and Adriana Vidal},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.160},

doi = {https://doi.org/10.1016/j.juro.2015.02.160},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e33-e33},

abstract = {INTRODUCTION AND OBJECTIVES: Pathologic Gleason 8–10 is associated with high risk of biochemical recurrence (BCR). However, whether there are subsets of men with Gleason 8–10 who have particularly high or low BCR risk is unknown. We examined predictors for early BCR (2-years) after radical prostatectomy (RP), among patients with pathological Gleason 8–10.



METHODS: We identified 459 patients treated with RP with pathologic Gleason 8–10 in the SEARCH database. Patients were stratified into 5 groups based on pathological characteristics – Group 1: men with negative surgical margins and no extracapsular extension (-SM/-ECE), Group 2 (+SM/-ECE), Group 3 (-SM/+ECE), Group 4 (+SM/+ECE), and Group 5: men with seminal vesicle invasion (+SVI). BCR was defined as a single PSA greater than 0.2 ng/ml, 2 values of 0.2 ng/ml, or secondary treatment for an elevated postoperative PSA. Cox proportional hazard models were used to compare early BCR (2-years post-RP) among groups and a log-rank test was used to assess the difference between survival curves by group.



RESULTS: At 2-years post-RP, patients in Group 5 (+SVI) had the highest BCR risk (66%) whereas men in Group 1 (-SM/-ECE) had the lowest risk (14%, p<0.001). No significant difference in recurrence among groups 2 to 4 (∼50% recurrence, log-rank, p=0.28) was found. On multivariable analysis after adjusting for PSA, age, pathological Gleason sum, and clinical stage; Group 5 had the highest recurrence risk, Groups 2–4 were at intermediate-risk with no differences among the groups, and Group 1 had the lowest risk of recurrence.



CONCLUSIONS: In patients with high grade (Gleason 8–10) prostate cancer after RP, the presence of surgical margins, extracapsular extension, both surgical margins and extracapsular extension, and seminal vesicle invasion are all associated with an increased risk of early BCR. While patients with seminal vesicle invasion are at the highest risk of recurrence, the presence of any of these pathological features among patients with Gleason 8–10 may warrant adjuvant radiation. On the contrary, men with organ-confined margin negative disease have a very low risk of early BCR despite Gleason 8–10 disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.1695,

title = {MP53-01 THE RELATIONSHIP OF OBESITY, PATHOLOGIC GLEASON GRADE AND PROSTATE CANCER TUMOR VOLUME AT THE TIME OF RADICAL PROSTATECTOMY—RESULTS FROM THE SEARCH DATABASE},

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

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.1695},

doi = {https://doi.org/10.1016/j.juro.2015.02.1695},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e635-e635},

abstract = {INTRODUCTION AND OBJECTIVES

Obesity has been associated with increased risk of prostate specific antigen (PSA) recurrence after radical prostatectomy (RP) and increased risk of prostate cancer (PCa) death. Whether poorer outcomes are entirely secondary to surgical technical challenges associated with obesity resulting in increased risk of positive margins, or due to an underlying aggressive PCa biology has not been completed elucidated. Thus, the objective of this study was to assess the relationship of obesity and objective measures of disease aggressiveness such as pathologic Gleason score and tumor volume (TV) in a multi−center, equal access cohort of patients.



METHODS

We retrospectively analyzed 3721 men from the SEARCH database who underwent RP from 1990 to 2013. Body mass index (BMI) groups were defined as: normal weight (<25kg/m2), overweight (25 to <30kg/m2), mildly obese (30 to <35kg/m2) and moderately + severely obese (≥35kg/m2). The association between BMI and pathologic Gleason sum (≥7 vs ≤6) was examined using logistic regression, adjusted for age, race, surgery year, PSA, and pathologic features. Logistic regression was also used to assess the association between BMI and other pathologic features (positive margins, extracapsular extension and seminal vesicle invasion), adjusted for age, race, surgery year, PSA, and biopsy Gleason. Adjusted mean and 95% confidence intervals of TV stratified by BMI were calculated from linear regression models.



RESULTS

There were 845 (23%) normal weight, 1,686 (45%) overweight, 869 (23%) mildly obese, and 321 (9%) moderately + severely obese patients. Patients with increasing BMI had a lower median serum PSA (p<0.001), and worse biopsy (p=0.001) and pathologic (p=0.02) Gleason disease. There was no difference in median TV (p=0.55) between the BMI groups on adjusted analysis. Moderately + severely obese patients (OR 1.47, 95%CI 1.06−2.05, p=0.02) were more likely to have pathologic Gleason ≥7 disease compared to normal weight patients (p−trend 0.02). BMI was not associated with positive margins (p−trend 0.07), extracapsular extension (p−trend 0.32), or seminal vesicle invasion (p−trend 0.22). After adjusting for baseline differences, we found that as BMI increased, adjusted mean TV increased (p−trend 0.02).



CONCLUSIONS

In this study of men undergoing RP at multiple equal access centers, obesity was associated with higher grade Gleason score and larger tumors. These results suggest that all else being equal, obese men may have biologically more aggressive tumors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.1696,

title = {MP53-02 IS CLINICAL STAGE T2C PROSTATE CANCER INTERMEDIATE OR HIGH-RISK DISEASE?},

author = {Zachary Klaassen and Abhay A Singh and Lauren E Howard and Zhaoyong Feng and Bruce Trock and Martha K Terris and William J Aronson and Matthew R Cooperberg and Christopher L Amling and Christopher J Kane and Alan Partin and Misop Han and Stephen J Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.1696},

doi = {https://doi.org/10.1016/j.juro.2015.02.1696},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e635-e635},

abstract = {INTRODUCTION AND OBJECTIVES

Clinical stage T2c (cT2c) is an indeterminate factor in the algorithm for prostate cancer (PC) risk stratification. According to D'Amico risk grouping and AUA guidelines, cT2c is high-risk, whereas NCCN and EAU classify cT2c as intermediate-risk. The objective of the study was to assess whether cT2c tumors, without other associated high-risk factors (cT2c not otherwise specified (cT2c-nos)), behave as intermediate or high-risk by analyzing biochemical recurrence (BCR) after radical prostatectomy (RP).



METHODS

We retrospectively analyzed 2,759 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. Comparisons in time to BCR between cT2c-nos and intermediate-risk, and high-risk patients were performed using log-rank test and Cox proportional analyses.



RESULTS

A total of 99 men (4%) from SEARCH and 202 (2%) from JHH were cT2c-nos. Patients with cT2c-nos had similar BCR risk as intermediate-risk (SEARCH p=0.27; JHH p=0.23), but significantly lower BCR risk vs. high-risk men (SEARCH p<0.001; JHH p<0.001). When specifically compared to intermediate and high-risk patients, and after adjusting for year and center, cT2c-nos patients had outcomes comparable to intermediate-risk (SEARCH p=0.44; JHH p=0.53), but significantly better than high-risk patients (SEARCH p=0.001; JHH p<0.001).



CONCLUSIONS

BCR risk for patients with cT2c disease without other high-risk features was comparable to men with intermediate-risk and significantly better than men with high-risk PC. These findings suggest men with cT2c PC should be offered treatment options for intermediate-risk PC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.1706,

title = {MP53-12 LONG TERM ONCOLOGICAL OUTCOMES OF APICAL POSITIVE SURGICAL MARGINS AT RADICAL PROSTATECTOMY IN THE SHARED EQUAL ACCESS REGIONAL CANCER HOSPITAL (SEARCH) COHORT},

author = {Harpreet Wadhwa and Martha Terris and William Aronson and Christopher Kane and Christopher Amling and Matthew Cooperberg and Stephen Freedland and Michael Abern},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.1706},

doi = {https://doi.org/10.1016/j.juro.2015.02.1706},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e640-e640},

abstract = {INTRODUCTION AND OBJECTIVES

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



METHODS

The SEARCH database was used to identify 2,625 men with prostate cancer (PCa) managed with RP and pelvic lymphadenectomy with complete pathologic grade and stage data. Men with positive lymph nodes were excluded. Margin status was categorized as negative, apex only, or other positive. Multivariable Cox regression models adjusted for pathologic stage and Gleason sum were developed to test the relationship between margin status and long-term oncologic outcomes (biochemical recurrence [BCR], metastases, PCa death).



RESULTS

In the final cohort 35.5% had PSM (6.0% apex only and 29.5% PSM at other locations) while 64.5% had negative surgical margins. At 78 months of median follow-up 891 men (33.9%) had BCR, 109 men (4.15%) developed metastases, and 64 men (2.44%) died of PCa. Univariable analysis showed that compared to negative margins, apex only PSM was associated with BCR (HR 1.52; 95% CI, 1.15-2.01), but not metastases or PCa death, while PSM at other locations were associated with increased likelihood for BCR (HR, 2.9; 95% CI, 2.53-3.32), metastases (HR 1.6; 95% CI, 1.11-2.43) and death (HR 1.9; 95% CI, 1.14-3.15). On multivariable analysis, apex only (HR 1.46; 95% CI, 1.11-1.93) and other positive margins (HR 2.1; 95% CI, 0.41-0.91) were associated with BCR but margin status was not associated with metastases or PCa death.



CONCLUSIONS

In multivariate analysis of large cohort of men undergoing RP, those with PSM at the prostatic apex were less likely to suffer BCR, metastases, or PCa death compared to those with PSM at other locations. When adjusted for pathologic stage and grade, however, PSM at any location were associated with BCR but not long term oncologic outcomes. These data suggest that men with apex only PSM may not be ideal candidates for adjuvant therapy after RP.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.2214,

title = {MP60-12 DOES LARGER TUMOR VOLUME EXPLAIN THE HIGHER PROSTATE SPECIFIC ANTIGEN LEVELS IN BLACK MEN WITH PROSTATE CANCER —RESULTS FROM THE SEARCH DATABASE},

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

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.2214},

doi = {https://doi.org/10.1016/j.juro.2015.02.2214},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e742-e742},

abstract = {INTRODUCTION AND OBJECTIVES

Multiple population-based studies have shown that black men have higher PSA values. Additionally, PSA is associated with larger prostate size and larger tumor size. We previously showed that the racial differences in PSA values are not explained by differences in prostate weight. An alternative explanation for higher PSA values among black men with prostate cancer may be increased tumor volume (TV). Thus, we assessed whether larger TV in black men explains the higher PSA levels in black versus white men with prostate cancer.



METHODS

We retrospectively analyzed 2099 men from the SEARCH database who underwent radical prostatectomy from 1990 to 2013. The associations between race and the outcome variables of TV and preoperative PSA values were examined using linear regression. We adjusted for center, age, surgery year, pathologic Gleason sum, positive margins, extracapsular extension, seminal vesicle invasion, and lymph node metastasis. Adjusted median and interquartile range of TV and PSA were calculated by back-transforming the predicted logarithmic values from the linear regression models.



RESULTS

There were 1236 (59%) white men and 863 (41%) black men. Black men were younger at surgery (60.3 vs. 63.1 years, p<0.001) had a higher preoperative PSA value (6.9 vs. 6.1 ng/mL, p<0.001), and more often had positive margins (48 vs. 38%, p<0.001) and seminal vesicle invasion (14 vs. 11%, p=0.03). White patients had worse clinical stage disease (p<0.001) and greater median TV (6.3 vs. 5.4 gm, p=0.004). After adjusting for demographics and cancer-specific characteristics, white men had a greater adjusted median TV (5.7 vs. 4.7 gm, p=0.02). However, when also adjusted for PSA, there was no racial difference in adjusted median TV (p=0.53). After adjusting for demographic and cancer-specific characteristics, black men had a higher median preoperative PSA compared to white men (7.5 vs. 6.1 ng/mL, p<0.001). To assess whether this difference was due to TV, we repeated the analysis of PSA but also adjusted for TV and again there was a significant difference in median preoperative PSA with black men having a 21% higher median preoperative PSA versus white men (7.4 vs. 6.1 ng/mL, p<0.001).



CONCLUSIONS

In this study of men undergoing radical prostatectomy at multiple equal access medical centers, TV did not explain the higher PSA levels in black versus white men. These results suggest that black men may have an inherent genetic profile that predisposes to higher PSA values regardless of demographic and clinicopathologic factors.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.534,

title = {MP82-15 DOES EARLY ANDROGEN DEPRIVATION THERAPY AFTER BIOCHEMICAL RECURRENCE FOLLOWING RADICAL PROSTATECTOMY INCREASE OVERALL SURVIVAL? RESULTS FROM SEARCH},

author = {Stephen Freedland and Lauren Howard and Christopher Amling and Matthew Cooperberg and Christopher Kane and Martha Terris and William Aronson},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.534},

doi = {https://doi.org/10.1016/j.juro.2015.02.534},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e1043-e1043},

abstract = {INTRODUCTION AND OBJECTIVES

Androgen deprivation therapy (ADT) is standard therapy for men with metastatic disease (mets) – whether they present with mets or mets develop after failed curative treatment. In the PSA era, a rising PSA is the first sign of recurrence after treatment and ADT is most often today begun prior to mets. Whether earlier initiation of ADT has a survival benefit remains hotly debated. We examined the relationship between early ADT and overall survival in men who had a biochemical recurrence (BCR) after radical prostatectomy (RP).



METHODS

We retrospectively analyzed data on 1,053 patients from 6 VA hospitals in the SEARCH database who had a BCR after RP between 1988 and 2013. Early ADT was defined as receiving ADT when PSA ≤5 ng/mL. Thus, the reference group contained patients who never received ADT or received late ADT (PSA >5 ng/mL). Cox models were used to test the association between early ADT and time from BCR to overall survival. Models were adjusted for age, race, surgical center, year of surgery, PSA, pathological Gleason score, time from surgery to recurrence, pathological features, and radiation therapy. In sensitivity analyses, we redefined early ADT as pre-ADT PSA ≤10 ng/mL or ≤20 ng/mL and also compared results for patients who did not receive ADT until time of mets.



RESULTS

Median follow-up after recurrence was 4.8 years. 219 patients (21%) had early ADT and 834 did not. On univariable analysis, early ADT was associated with decreased risk of death (HR 0.74, p=0.010). After adjusting for imbalances between the two groups, early ADT remained associated with decreased risk of death (HR 0.72, p=0.021). When early ADT was redefined as pre-ADT PSA ≤10 ng/mL, this association remained on multivariable analysis (HR 0.79, p=0.045). However, when early ADT was defined as pre-ADT PSA ≤20 ng/mL, the association between early ADT and overall survival was no longer significant (HR 0.83, p=0.107). ADT did not show a statistically significant survival benefit among those who received ADT at time of mets (HR 0.74, p=0.152).



CONCLUSIONS

We found an overall survival benefit for men with BCR after RP if ADT was initiated before PSA reaches 10 ng/mL, and this benefit was stronger when ADT was initiated before PSA reaches 5 ng/mL. While the survival benefits of ADT must be weighed against long-term side effects, our data support treating with ADT before the time of mets in order to increase overall survival. Further studies are warranted to support these findings.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.1953,

title = {MP87-08 IS COMPUTERIZED TOMOGRAPHY A NECESSARY PART OF A PROSTATE CANCER METASTATIC WORKUP? RESULTS FROM SEARCH},

author = {Brian Hanyok and Lauren Howard and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/10.1016/j.juro.2015.02.1953},

doi = {https://doi.org/10.1016/j.juro.2015.02.1953},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e1087-e1087},

abstract = {INTRODUCTION AND OBJECTIVES

With bone being the most common site for prostate cancer (PC) metastases, the bone scan plays a central role in a metastatic workup. Recently, awareness has grown of the different biology and outcomes associated with soft tissue metastases, which has led to the integration of computerized tomography (CT) into the workup for advanced disease. Also, some new PC drugs are contraindicated in men with soft tissue metastases, providing further impetus to screen with CT. Currently, few data exist regarding the frequency of CT use and the prevalence of soft tissue metastases detected by CT during a metastatic workup for PC.



METHODS

We analyzed 204 men from two VA centers of the SEARCH database with non-metastatic castration-resistant prostate cancer (M0 CRPC) from 2000-2013 who later had metastases detected by a bone scan or CT. Data were collected on any follow-up bone scan or CT within 30 days of the initial metastasis diagnosis. Imaging tests were classified as positive or negative for bone metastases or soft tissue metastases. Characteristics were compared between those who received a bone scan vs. those who received a bone scan and CT using chi-square and rank sum as appropriate. Men who had a CT only were excluded due to small numbers (n=25). A logistic model to predict soft tissue metastases was fit among those who received both a bone scan and CT. Predictors included age, year, race, treatment center, PSA, PSA doubling time (PSADT), and time from CRPC to metastasis diagnosis. This model was then used to predict the number of missed soft tissue metastases among those who only received a bone scan.



RESULTS

Compared to men who had both a bone scan and CT (n=88), men who had only a bone scan (n=116) were older, had earlier year of metastases, and were more likely to be from VA center 2 (all p<0.03). There were no differences in race, PSA, PSADT, or time from CRPC to metastases. Of those who received a bone scan and CT, 59 (67%) had bone metastases only and 29 (33%) had soft tissue metastases or both bone and soft tissue. Our model predicted that 20 (17%) of the men who only had a bone scan would have had soft tissue metastases had they gotten a CT with their bone scan.



CONCLUSIONS

Our model suggests that foregoing a CT scan during metastatic workup leads to underdiagnosis of soft tissue metastases in a notable number of men, potentially leading to insufficient or unsuitable medical care. If CT scans were performed in all men with M0 CRPC at the time of metastatic disease, our data suggest nearly 1 in 4 would have soft tissue metastasis, arguing that CT scan should be routinely used for metastatic evaluation of men with M0 CRPC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.1954,

title = {MP87-09 WHEN IS AN EQUIVOCAL BONE SCAN NOT REALLY EQUIVOCAL? RESULTS FROM SEARCH},

author = {Brian Hanyok and Lauren Howard and Christopher Amling and William Aronson and Matthew Cooperberg and Christopher Kane and Martha Terris and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.1954},

doi = {https://doi.org/10.1016/j.juro.2015.02.1954},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e1087-e1087},

abstract = {INTRODUCTION AND OBJECTIVES

Often, bone scans are equivocal: neither definitive for metastases nor definitively normal. As few studies describe the likelihood of a positive follow-up imaging test after an equivocal bone scan, no guidelines exist on when to conduct repeat imaging after an equivocal scan. Thus, we examined outcomes and predictors of follow-up imaging results after an equivocal bone scan in men with non-metastatic castration-resistant prostate cancer (M0 CRPC).



METHODS

We collected data on men from two VA hospitals in the SEARCH database that had an equivocal bone scan after diagnosis of M0 CRPC from 2000-2013. The equivocal bone scan was rated as “low-risk equivocal” if the radiology report identified prostate cancer (PC) metastases as possible but unlikely or if the scan was labelled abnormal with no further elaboration, and “high-risk equivocal” if PC metastases were deemed most likely out of two or more possible diagnoses. Charts were reviewed to find all follow-up imaging (bone scan, CT, MRI, and/or X-ray) pertaining to the equivocal lesions within 3 months of the equivocal scan. Outcome was determined from the worst interpretation of all follow-up imaging tests. Logistic regression was used to test predictors of an equivocal scan being proven positive within 3 months.



RESULTS

Of 459 men who underwent imaging, 58 (13%) had an equivocal bone scan. Follow-up imaging tests among the 58 men included 4 bone scans, 5 MRIs, 4 CTs, and 17 X-rays. Of 51 men who had a low-risk equivocal bone scan, 18 (35%) had follow-up imaging of which 3 (17%) were positive. In contrast, of 7 men with a high-risk equivocal bone scan, 6 (86%) had follow-up imaging of which 3 (50%) were positive. There was no association between positive follow-up imaging and PSA (p=0.52) or PSA doubling time (p=0.88). High-risk equivocal scan was associated with increased risk of positive follow-up imaging, though this did not reach statistical significance (HR 12.0, p=0.06).



CONCLUSIONS

We found equivocal bone scans were later deemed positive in only 25% of M0 CRPC patients who receive follow-up imaging tests within 3 months. For low-risk equivocal men, <20% had a positive follow-up imaging test, while 50% of high-risk men had a positive follow-up imaging test. While numbers are small and require confirmation, if validated, these findings suggest follow-up imaging tests for men with low-risk equivocal scans can be delayed while high-risk equivocal scans should receive immediate follow-up imaging.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.2121,

title = {PD32-10 POSITIVE SURGICAL MARGINS IN RADICAL PROSTATECTOMY PATIENTS DO NOT PREDICT LONG-TERM ONCOLOGICAL OUTCOMES: RESULTS FROM SEARCH},

author = {Prabhakar Mithal and Lauren Howard and William Aronson and Martha Terris and Matthew Cooperberg and Christopher Kane and Christopher Amling and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.2121},

doi = {https://doi.org/10.1016/j.juro.2015.02.2121},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e708-e708},

abstract = {INTRODUCTION AND OBJECTIVES

Positive surgical margins (PSMs) at radical prostatectomy (RP) are often used as indication for adjuvant therapy as PSMs are associated with biochemical recurrence (BCR). However, the impact of PSMs on metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM) are unclear. We assessed whether PSMs predict long-term outcomes after RP.



METHODS

Retrospective study of 4,051 men in SEARCH treated by RP from 1988-2013. Proportional hazard models were used to estimate hazard ratios of PSMs in predicting BCR, CRPC, metastases, and PCSM. To determine if PSMs were more predictive of these outcomes in certain patients, analyses were stratified by pathological Gleason score, stage, and pre-operative PSA.



RESULTS

Median follow-up was 6.6 years (IQR 3.2-10.6) and 1,127 patients had over 10 years of follow-up. During this time, 1,302 (32%) men experienced BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died of PC. 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, margins were associated with increased risk of only BCR (HR 1.98, p<0.001), and not CRPC, metastases, or PCSM (HR ≤1.20, p>0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA, and when patients who underwent adjuvant therapy 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 should not be used as an indication for adjuvant treatment.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.2243,

title = {PD34-07 CAN GLEASON 7 PROSTATE CANCER EVER BE LOW-RISK? RESULTS FROM THE SHARED EQUAL ACCESS REGIONAL CANCER HOSPITAL (SEARCH) DATABASE},

author = {Kathleen McGinley and Xizi Sun and Lauren Howard and William Aronson and Martha Terris and Christopher Kane and Christopher Amling and Matthew Cooperberg and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.2243},

doi = {https://doi.org/10.1016/j.juro.2015.02.2243},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e757-e757},

abstract = {INTRODUCTION AND OBJECTIVES

Overtreatment of low-risk prostate cancer (PC) is a major issue. Increasing use of active surveillance (AS) will ease this burden. Limited data are available on including men with intermediate risk PC (i.e. Gleason 7) into AS protocols. We examined if a subset of men with Gleason 7 (3+4) PC could be reasonable AS candidates.



METHODS

We used the SEARCH Database to identify men who had radical prostatectomy from 2001-13 with >8 cores on biopsy and complete data. We compared men who had low-risk disease (cT1c/T2a; biopsy Gleason ≤6; PSA ≤10 ng/mL) vs. men who had low-risk features (cT1c/T2a; PSA ≤10 ng/mL) with the exception of biopsy Gleason 7 (3+4). Logistic regression models were used to test the association between biopsy Gleason 3+4 vs. ≤6 and pathological features. Biochemical recurrence (BCR) was examined using multivariable Cox hazards analysis adjusted for clinical and demographic features. To examine if there was a subset of men with low-volume Gleason 7 who would have comparable outcomes to low-risk men, we repeated all analyses limiting the percent positive cores to ≤ 33% and number of positive cores to ≤ 4, ≤ 3, or ≤ 2.



RESULTS

874 men met inclusion criteria: 497 had low-risk PC and 377 had Gleason 7 low-risk PC. The Gleason 7 low-risk men had increased risk of pathological Gleason ≥4+3 (p<0.001), positive margins (p=0.079), extracapsular extension (p<0.001), and seminal vesicle invasion (p<0.001) on univariable analysis. Men in the Gleason 7 low-risk group had significantly higher BCR risk (HR 1.67, p=0.003). Analyses were repeated using increasingly strict definitions of low-volume PC. With the exception of higher pathological Gleason score (p<0.001), at ≤3 positive cores, there were no differences in adverse pathological features between groups (all p>0.1). Among men with ≤3 positive cores who met the other low-risk criteria (cT1c/T2a; PSA ≤10 ng/mL), BCR risk was similar in men with Gleason 6 or Gleason 7 (3+4) PC (HR 1.30; p=0.347).



CONCLUSIONS

Among men with PSA ≤10 ng/mL and stage cT1c/T2a, those with Gleason 7 (3+4) PC in ≤3 positive cores have similar rates of adverse pathology and BCR as men with Gleason ≤6 PC. If confirmed, this finding may expand inclusion criteria of AS protocols to reduce PC overtreatment.



},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2015.02.2432,

title = {PD38-11 ADVERSE PATHOLOGY YET UNDETECTABLE ULTRASENSITIVE PSA: IS ADJUVANT RADIATION REALLY NECESSARY?},

author = {Ross Simon and Lauren Howard and Stephen Freedland and William Aronson and Martha Terris and Christopher Kane and Christopher Amling and Matthew Cooperberg and Adriana Vidal},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2015.02.2432},

doi = {https://doi.org/10.1016/j.juro.2015.02.2432},

year  = {2015},

date = {2015-01-01},

journal = {Journal of Urology},

volume = {193},

number = {4S},

pages = {e829-e829},

abstract = {INTRODUCTION AND OBJECTIVES

Men with adverse pathology (positive margins, extraprostatic extension, and seminal vesicle invasion) are at increased risk of biochemical recurrence (BCR) after radical prostatectomy (RP) and are candidates for adjuvant radiation based on the AUA/ASTRO guideline. In contrast, men with an undetectable ultrasensitive PSA (<0.01) after RP have lower rates of BCR when compared to patients with detectable PSA, or undetectable PSA defined by a less-sensitive assay. As such, we assessed BCR outcomes among men with a mismatch; adverse pathology but an undetectable ultrasensitive post-RP PSA, to determine risk factors associated with BCR and to identify suitable candidates for adjuvant radiation.



METHODS

We evaluated 411 patients treated with RP from 2001 to 2013 from the SEARCH database who had an undetectable ultrasensitive post-RP PSA (<0.01) with positive margins, extraprostatic extension, and/or seminal vesicle invasion. Men treated with androgen deprivation or radiation therapy were excluded. BCR was defined as a single PSA >0.2ng/ml, 2 concentrations at 0.2ng/mL, or secondary treatment for elevated PSA. Multivariable Cox regression analyses were utilized to test the relationship between pathologic characteristics and early BCR (within 3-years of RP) as these patients were more likely to die from prostate cancer compared to patients who recurred after 3 years.



RESULTS

Among patients with adverse pathology and undetectable ultrasensitive post-RP PSA, only pathologic Gleason 7 (4+3), Gleason ≥8, and seminal vesicle invasion were independent predictors of BCR (HR 2.21, p=0.019; HR 3.53, p<0.001; and HR 2.94, p=0.001). However, in terms of 3-year BCR, men with Gleason 7 (4+3) did not have statistically different rates of BCR when compared to men with Gleason 6 (20% vs. 11.4 %, p=0.074). On the contrary, men with Gleason ≥8 (with positive margins or extraprostatic extension) or seminal vesicle invasion (19% of the cohort) defined a group with higher rates of 3-year BCR when compared to patients without those characteristics (50.4% vs. 11.9%, p<0.001).



CONCLUSIONS

Among men with adverse pathology but with an undetectable ultrasensitive post-operative PSA (<0.01), the benefits of adjuvant radiation are likely limited, except for a small group of men with Gleason 8-10 (with positive margins or extracapsular extension) or seminal vesicle invasion who are at high-risk of early BCR and subsequent death from prostate cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2014.02.1186,

title = {MP42-09 PREDICTING BONE SCAN POSITIVITY IN CASTRATION-RESISTANT PROSTATE CANCER},

author = {Daniel Moreira and Lauren Howard and Katie Sourbeer and Robert Kundich and Christopher Kane and William Aronson and Martha Terris and Matthew Cooperberg and Christopher Amling and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2014.02.1186},

doi = {https://doi.org/10.1016/j.juro.2014.02.1186},

year  = {2014},

date = {2014-01-01},

journal = {Journal of Urology},

volume = {191},

number = {4S},

pages = {e471-e471},

abstract = {Introduction and Objectives: Men with non-metastatic castration-resistant prostate cancer (CRPC) are at high risk of developing metastasis. Bone scans are routinely used to detect metastasis, however most scans are negative. PSA levels and kinetics such as PSA doubling time (PSADT) and velocity (PSAV) have been correlated with bone scan positivity in these patients; however it is unknown at which PSA and kinetics bone scan screening should start. Also, it is unclear how absolute PSA and PSA kinetics can be used in concert to estimate the positive scans. We examined PSA levels and kinetic cutoffs to predict positive bone scans for men from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.



Methods: Retrospective analysis of 367 bone scans of 122 clinically CRPC patients with no known metastases at baseline in the SEARCH database. These men were treated with a variety of primary treatment types. Once a scan was positive, no further scans were included for that patient. The association of patients’ demographics, pathological features, PSA levels and PSA kinetics with risk of a positive scan was done with generalized estimating equations.



Results: A total of 104 (28%) scans were positive. Positive scans were associated with younger age (OR=0.976; P=0.023), higher biopsy Gleason (P=0.028), higher pre-scan PSA (OR=2.21; P<0.001), shorter pre-scan PSADT (OR=0.98; P<0.001), higher PSAV (OR=1.80; P<0.001) and more recent scan year (OR=0.92; P=0.013). The scan positivity was 7%, 11%, 32% and 53% for men with PSA <5, 5-14.9, 15-49.9 and >=50ng/mL, respectively (P-trend <0.001). Men with PSADT <3, 3-8.9, 9-14.9 and >=15 months had a scan positivity of 16%, 30%, 35% and 55%, correspondingly (P-trend <0.001). Tables were constructed using PSA and PSADT to predict the risk of a positive scan (Table).



Conclusions: In a cohort of CRPC men undergoing bone scans for metastasis detection, PSA levels and PSA kinetics were associated with positive bone scans. Specifically, we developed tables to predict the risk of a positive bone scan by PSA and PSADT. Thus, the combination of absolute PSA levels and PSA kinetics may be used to select patients for bone scans potentially reducing the number of unnecessary scans.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2014.02.2486,

title = {MP78-03 PREDICTORS OF TIME TO METASTASIS IN NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER},

author = {Daniel Moreira and Lauren Howard and Katie Sourbeer and Robert Kundich and Christopher Kane and William Aronson and Martha Terris and Matthew Cooperberg and Christopher Amling and Stephen Freedland},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2014.02.2486},

doi = {https://doi.org/10.1016/j.juro.2014.02.2486},

year  = {2014},

date = {2014-01-01},

journal = {Journal of Urology},

volume = {191},

number = {4S},

pages = {e921-e921},

abstract = {INTRODUCTION AND OBJECTIVES: Men with non-metastatic castration-resistant prostate cancer (CRPC) have worse prognosis than their hormone-sensitive counterparts and are at high risk of developing metastasis. Few studies examined the natural history of these patients. In addition, the factors associated with rapid progression to metastatic disease are largely unknown. Therefore, we investigated the predictors of time to metastasis among men treated with androgen deprivation therapy (ADT) either as primary or salvage treatment who developed CRPC within the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort.



METHODS: Retrospective analysis of 259 clinically CRPC men with no known metastases in the SEARCH database. Metastases were detected using routine imaging studies. Predictors of time to metastasis diagnosis were analyzed using proportional hazards model with time of CRPC diagnosis as time zero.



RESULTS: 188 (73%) men develop metastatic disease over a median follow-up of 38 months. Median time from CRPC to metastasis was 15 months. Metastasis-free survival was 68%, 48%, 33%, 26% and 20% at 1, 2 3, 4 and 5 years after CRPC, respectively. In univariable analysis, shorter time from CRPC to metastasis was associated with high Gleason scores (P<0.001), higher PSA at CRPC diagnosis (P<0.001) and shorter time from ADT to CRPC (P=0.010). In multivariable analysis, Gleason score 7 (HR=2.19; P=0.002) and 8-10 (HR=2.00; P=0.005), higher PSA at CRPC diagnosis (logPSA HR=1.45; P<0.001) and shorter time from ADT to CRPC (HR=0.90; P=0.004) were independently associated with shorter time from CRPC to metastasis. Similar results were found when these variables were divided in 3 groups (figure). There was a trend toward shorter time to metastasis with shorter time from cancer diagnosis to ADT (univariable P=0.051, multivariable P=0.057). Age, race, primary cancer treatment and CRPC year were not associated with time to metastasis.



CONCLUSIONS: In a cohort of CRPC men with no known metastasis, 80% were diagnosed with metastatic disease during the first 5 years after CRPC with most metastasis occurring within the first 2 years. Higher Gleason score, higher PSA and shorter time from ADT to CRPC were independently associated with shorter time to metastasis. Therefore, these variables can be used to stratify patients according to the risk of metastasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{doi:10.1016/j.juro.2014.02.2266,

title = {PD31-07 AGENT ORANGE AND LONG-TERM OUTCOMES AFTER RADICAL PROSTATECTOMY},

author = {Aaron E Ovadia and Michael R Abern and William J Aronson and Christopher J Kane and Christopher L Amling and Matthew R Cooperberg and Stephen J Freedland and Martha K Terris},

url = {https://www.auajournals.org/doi/pdf/10.1016/j.juro.2014.02.2266},

doi = {https://doi.org/10.1016/j.juro.2014.02.2266},

year  = {2014},

date = {2014-01-01},

journal = {Journal of Urology},

volume = {191},

number = {4S},

pages = {e833-e834},

abstract = {INTRODUCTION AND OBJECTIVES: Currently the evidence linking Agent Orange (AO) to prostate cancer (PC) is limited and conflicting. While studies have demonstrated that AO is a risk factor for adverse pathology and biochemical recurrence, the relationship between AO exposure and long-term outcomes are unknown.



METHODS: Data from 1,882 men undergoing radical prostatectomy (RP) for PC were analyzed from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Men were classified based on self-reported AO exposure. Predictors of biopsy and pathologic Gleason sum (GS) ≥8, and advanced pathologic stage were determined by logistic regression models adjusted for several pre-operative factors (age, race, clinical stage, PSA, and BMI). Biochemical recurrence (BCR), metastases, and PC specific mortality were determined by Cox proportional hazards adjusted for pre-operative factors as well as center and biopsy GS.



RESULTS: There were 333 (17.7%) men who had AO exposure. AO exposed men were younger (median 59 vs. 62 years), had lower preoperative PSA (5.8 vs. 6.7 ng/mL) and clinical stage (25 vs. 39% palpable), and higher BMI (28.2 vs. 27.6 kg/m2), all p<0.01. Biopsy GS did not differ. Pathologic GS, rate of positive margins and positive lymph nodes, and extracapsular extension did not differ, however men with AO exposure had a lower rate of seminal vesicle invasion (7.0 vs. 10.9%,p=0.04). At a median follow-up of 85 months, 702 (37.4%) of patients had BCR, 78 (4.1%) had metastases, and 39 (2.1%) died from PC. On multivariable analysis, AO exposure was not associated with BCR, metastases, or PC mortality.



CONCLUSIONS: In this cohort of PC patients treated with RP, AO exposure was not associated with worse preoperative characteristics such as elevated PSA or biopsy GS, nor was it associated with worse postoperative long-term outcomes of metastases or PC death. Thus, as the data on AO exposed men matures, possible differences in PC outcomes observed in earlier publications are no longer apparent.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

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

author = {Roberto Lodeiro Muller and Joseph C. Presti and William J Aronson and Martha K. Terris and Christopher J Kane and Christopher L Amling and Stephen J. Freedland},

doi = {https://ascopubs.org/doi/abs/10.1200/jco.2012.30.5_suppl.203},

year  = {2012},

date = {2012-02-01},

urldate = {2012-02-01},

journal = {Journal of Clinical Oncology},

volume = {30},

number = {5},

pages = {203},

abstract = {Background: SRT offers a second opportunity for PCa control after biochemical recurrence in men treated with radical prostatectomy. Although some retrospective data suggest an overall survival benefit, we hypothesized that in men with radio-resistant tumors, SRT may indeed promote transformation to a more aggressive cancer due to radiation-induced mutations. To test this, we used PSADT as a surrogate for cancer aggressiveness and compared PSADT before and after SRT in men who failed SRT. 

 

Methods: Of 288 men who underwent SRT in the Shared Equal Access Regional Cancer Hospital (SEARCH) database since 1988, we detected 78 with SRT failure defined as PSA ≥ 0.2 ng/mL above the post-SRT nadir. Of these, 44 had PSADT available before and after SRT, which was compared using Wilcoxon’s paired test with men serving as their own controls. We also tested predictors of PSADT change using multivariable logistic regression. 

 Results: There were no differences in PSADT before and after SRT (10.6 vs. 12.2 months; P=0.85). 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=0.067). 

 

Conclusions: Overall, the PSADT after and before SRT were statistically similar suggesting that after SRT failure, PCa does not emerge with more aggressive biologic features. Further studies are needed to identify predictors and the clinical relevance of individual PSADT changes noted in our study. (Note: Authors R. L. Muller and S. J. Freedland received support from DoD Award Number W81XWH-10-1-0155).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kane2008,

title = {OUTCOMES AFTER RADICAL PROSTATECTOMY AMONG MEN WHO ARE CANDIDATES FOR ACTIVE SURVEILLANCE: RESULTS FROM THE SEARCH DATABASE},

author = {Christopher J Kane, Martha K Terris, William J Aronson, Joseph C Presti, Christopher L Amling, and Stephen J Freedland},

doi = {https://doi.org/10.1016/S0022-5347(08)61902-3},

year  = {2008},

date = {2008-04-01},

journal = {The Journal of Urology},

volume = {179},

number = {4S},

pages = {651},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freedland2008,

title = {OVER THE LAST 15+ YEARS, THE PERCENTAGE OF MEN UNDERGOING RADICAL PROSTATECTOMY WHO ARE CANDIDATES FOR ACTIVE SURVEILLANCE HAS NOT CHANGED: RESULTS FROM THE SEARCH DATABASE},

author = {Stephen J Freedland, Martha K Terris, William J Aronson, Joseph C Presti, Christopher L Amling, and Christopher J Kane},

url = {Abstract (1899): https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2808%2961907-2},

doi = {https://doi.org/10.1016/S0022-5347(08)61907-2},

year  = {2008},

date = {2008-04-01},

journal = {The Journal of Urology},

volume = {179},

number = {4S},

pages = {653},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freedland2007,

title = {Obesity, Risk of Biochemical Recurrence, and PSADT after Radical Prostatectomy},

author = {Stephen J. Freedland, Robert J. Hamilton, William J. Aronson, Martha K. Terris, Joseph C. Presti, Christopher L. Amling, and Christopher J. Kane},

url = {Abstract 459; https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2818%2930712-2},

doi = {https://doi.org/10.1016/S0022-5347(18)30712-2},

year  = {2007},

date = {2007-04-01},

journal = {The Journal of Urology},

volume = {177},

number = {4S},

pages = {154},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freedland2006,

title = {Upgrading and Downgrading of Prostate Needle Biopsies: Risk Factors and Clinical Implications},

author = {Stephen J. Freedland, Christopher J. Kane, Christopher L. Amling, William J. Aronson, Martha K. Terris, and Joseph C. Presti},

url = {Abstract (1654): https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2818%2933846-1},

doi = {https://doi.org/10.1016/S0022-5347(18)33846-1},

year  = {2006},

date = {2006-04-01},

journal = {The Journal of Urology},

volume = {175},

number = {4S},

pages = {534},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kane2005,

title = {High-Risk Patients Undergoing Radical Prostatectomy Today are Less High-Risk than in the Past},

author = {Christopher J. Kane, Martha K. Terris, William J. Aronson, Joseph C. Presti, Christopher L. Amling, and Stephen J. Freedland},

doi = {https://doi.org/10.1016/S0022-5347(18)35732-X},

year  = {2005},

date = {2005-04-01},

journal = {The Journal of Urology},

volume = {173},

number = {4S},

pages = {436},

abstract = {INTRODUCTION AND OBJECTIVE: Dramatic changes have occurred in

prostate cancer over the last 10-15 years. We sought to examine the impact of these

changes on the nature and outcomes of high-risk men undergoing radical

prostatectomy (RP). 

METHODS: From 1991 to 2003, 136 men with high-risk prostate cancer (PSA

>20 nglml and/or biopsy Gleason >7) were identified from a cohort of 921 men

(15%) enrolled in the SEARCH Database. Temporal changes in the

clinicopathological characteristics and PSA recurrence rates following RP were

examined stratified by 4-year blocks of time. 

RESULTS: Over time, significantly more men were considered high-risk due

to a high biopsy Gleason score relative to prior years where the most common reason for being considered high-risk was an elevated PSA (p<O.OOl). No patient

from 2000 to 2003 had both an elevated PSA (>20 nglml) and high biopsy Gleason

sum (>7) compared to 15% from 1991 to 1995. Over time, there were no

differences in biochemical recurrence rates (p=0.36). There was a trend for men

with both a high biopsy Gleason score and an elevated PSA to have worse

outcomes relative to men with just a high Gleason score (p=O.lO) or men with just

a high serum PSA (p=O.ll). On multivariate analysis, higher serum PSA

(p=0.03), higher biopsy Gleason sum (p=0.002) and higher clinical stage

(p=0.04) were independently associated with biochemical recurrence.

CONCLUSIONS: Over time, the reasons for being classified as high-risk have

shifted. Most high-risk men today are high-risk due to an elevated Gleason sum.

The changing nature of the high-risk patient makes temporal comparisons of

outcomes among tightly defined groups such as "high-risk" patients problematic.

Source of Funding: Department of Veterans Affairs; The Georgia Cancer

Coalition; DOD, Prostate Cancer Research Program; AFUD/AUAER Scholarship

Award.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freedland2004,

title = {Men with Normal Pre-Operative Serum PSA Values have Better Biochemical Outcomes Following Radical Prostatectomy},

author = {Stephen J. Freedland, William J. Aronson, Christopher J. Kane, Martha K. Terris, Joseph C. Presti, Bruce Track, and Christopher L. Amling},

url = {Abstract (1262) : https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2818%2938487-8},

doi = {https://doi.org/10.1016/S0022-5347(18)38487-8},

year  = {2004},

date = {2004-04-01},

journal = {The Journal of Urology},

volume = {171},

number = {4S},

pages = {332},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freedland2004b,

title = {Percent of Prostate Needle Biopsy Cores with Cancer from the Most Involved Side of the Biopsy is a Better Predictor of PSA Recurrence Following Radical Prostatectomy than the Total Percent of Cores with Cancer},

author = {Stephen J. Freedland, William J. Aronson, Martha K. Terris, Christopher J. Kane, Christopher L. Amling, Frederick Dorey, and Joseph C. Presti},

url = {Abstract 1038: https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2818%2938275-2},

doi = {https://doi.org/10.1016/S0022-5347(18)38275-2},

year  = {2004},

date = {2004-04-01},

journal = {The Journal of Urology},

volume = {171},

number = {4S},

pages = {274},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freedland2004c,

title = {Obesity is an Independent Predictor of Biochemical Failure Following Radical Prostatectomy},

author = {Stephen J. Freedland, William J. Aronson, Christopher J. Kane, Joseph C. Presti, Christopher L. Amling, David Elashoff, and Martha K. Terris},

url = {Abstract 437: https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2818%2937699-7},

doi = {https://doi.org/10.1016/S0022-5347(18)37699-7},

year  = {2004},

date = {2004-04-01},

journal = {The Journal of Urology},

volume = {171},

number = {4S},

pages = {115-116},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Freedland2004cb,

title = {Obesity is an Independent Predictor of Biochemical Failure Following Radical Prostatectomy},

author = {Stephen J. Freedland, William J. Aronson, Christopher J. Kane, Joseph C. Presti, Christopher L. Amling, David Elashoff, and Martha K. Terris},

url = {Abstract 437: https://www.auajournals.org/doi/pdf/10.1016/S0022-5347%2818%2937699-7},

doi = {https://doi.org/10.1016/S0022-5347(18)37699-7},

year  = {2004},

date = {2004-04-01},

journal = {The Journal of Urology},

volume = {171},

number = {4S},

pages = {115-116},

keywords = {},

pubstate = {published},

tppubtype = {article}

}