Search

PurposeRacial disparities in the incidence and risk profile of prostate cancer at diagnosis among African-American men are well reported. However, it remains unclear whether African-American race is independently associated with adverse outcomes in men with clinical low risk disease.Materials and methodsWe retrospectively analyzed the records of 895 men in the SEARCH (Shared Equal Access Regional Cancer Hospital) database in whom clinical low risk prostate cancer was treated with radical prostatectomy. Associations of African-American and Caucasian race with pathological biochemical recurrence outcomes were examined using chi-square, logistic regression, log rank and Cox proportional hazards analyses.ResultsWe identified 355 African-American and 540 Caucasian men with low risk tumors in the SEARCH cohort who were followed a median of 6.3 years. Following adjustment for relevant covariates African-American race was not significantly associated with pathological upgrading (OR 1.33, p = 0.12), major upgrading (OR 0.58, p = 0.10), up-staging (OR 1.09, p = 0.73) or positive surgical margins (OR 1.04, p = 0.81). Five-year recurrence-free survival rates were 73.4% in African-American men and 78.4% in Caucasian men (log rank p = 0.18). In a Cox proportional hazards analysis model African-American race was not significantly associated with biochemical recurrence (HR 1.11, p = 0.52).ConclusionsIn a cohort of patients at clinical low risk who were treated with prostatectomy in an equal access health system with a high representation of African-American men we observed no significant differences in the rates of pathological upgrading, up-staging or biochemical recurrence. These data support continued use of active surveillance in African-American men. Upgrading and up-staging remain concerning possibilities for all men regardless of race.

ObjectivesTo test the external validity of a previously developed risk table, designed to predict the probability of a positive bone scan among men with non-metastatic (M0) castration-resistant prostate cancer (CRPC), in a separate cohort.Patients and methodsWe retrospectively analysed 429 bone scans of 281 patients with CRPC, with no known previous metastases, treated at three Veterans Affairs Medical Centers. We assessed the predictors of a positive scan using generalized estimating equations. Area under the curve (AUC), calibration plots and decision-curve analysis were used to assess the performance of our previous model to predict a positive scan in the current data.ResultsA total of 113 scans (26%) were positive. On multivariable analysis, the only significant predictors of a positive scan were log-transformed prostate-specific antigen (PSA): hazard ratio (HR) 2.13; 95% confidence interval (CI) 1.71-2.66 (P < 0.001) and log-transformed PSA doubling time (PSADT): HR 0.53; 95% CI 0.41-0.68 (P < 0.001). Among men with a PSA level

ObjectiveTo investigate predictors of time to metastasis among men treated with androgen deprivation therapy for nonmetastatic prostate cancer who developed castration-resistant prostate cancer (CRPC) within the Shared Equal Access Regional Cancer Hospital cohort.MethodsThis is a retrospective analysis of 458 nonmetastatic CRPC men. Metastases were detected in routine bone scans or other imaging tests. Predictors of time to metastasis were analyzed using proportional hazards model with CRPC as time zero.ResultsA total of 256 (56%) men were diagnosed with metastatic disease over a median follow-up of 36 months. Metastasis-free survival was 79%, 65%, 52%, 47%, and 41% at 1, 2, 3, 4, and 5 years after CRPC, respectively. In multivariable analysis, Gleason score 8-10 (hazard ratio [HR] = 1.61; P = .026), receiving primary localized treatment (HR = 1.38; P = .028), higher prostate-specific antigen (PSA) levels at CRPC diagnosis (logPSA HR = 1.64; P

ObjectiveTo determine whether there are subsets of men with pathological high grade prostate cancer (Gleason score 8-10) with particularly high or low 2-year biochemical recurrence (BCR) risk after radical prostatectomy (RP) when stratified into groups based on combinations of pathological features, such as surgical margin status, extracapsular extension (ECE) and seminal vesicle invasion (SVI).Materials and methodsWe identified 459 men treated with RP with pathological Gleason score 8-10 prostate cancer in the SEARCH database. The men were stratified into five groups based on pathological characteristics: group 1, men with negative surgical margins (NSMs) and no ECE; group 2, men with positive surgical margin (PSMs) and no ECE; group 3, men with NSMs and ECE; group 4, men with PSMs and ECE; and group 5, men with SVI. Cox proportional hazards models and the log-rank test were used to compare BCR among the groups.ResultsAt 2 years after RP, pathological group was significantly correlated with BCR (log-rank, P < 0.001) with patients in group 5 (+SVI) having the highest BCR risk (66%) and those in group 1 (NSMs and no ECE) having the lowest risk (14%). When we compared groups 2, 3, and 4, with each other, there was no significant difference in BCR among the groups (~50% 2-year BCR risk; log-rank P = 0.28). Results were similar when adjusting for prostate-specific antigen, age, pathological Gleason sum and clinical stage, or after excluding men who received adjuvant therapy.ConclusionsIn patients with high grade (Gleason score 8-10) prostate cancer after RP, the presence of either PSMs, ECE or SVI was associated with an increased risk of early BCR, with a 2-year BCR risk of ≥50%. Conversely, men with organ-confined margin-negative disease had a very low risk of early BCR despite Gleason score 8-10 disease.

ObjectivesTo determine if men with adverse pathology but undetectable ultrasensitive (

BackgroundBlack men are disproportionately affected by both cardiovascular disease and prostate cancer. Epidemiologic evidence linking dyslipidemia, an established cardiovascular risk factor, and prostate cancer progression is mixed. As existing studies were conducted in predominantly non-black populations, research on black men is lacking.MethodsWe identified 628 black and 1,020 non-black men who underwent radical prostatectomy and never used statins before surgery in the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Median follow-up was 2.9 years. The impact of preoperative hypercholesterolemia on risk of biochemical recurrence was examined using multivariable, race-stratified proportional hazards. In secondary analysis, we examined associations with low-density lipoprotein (LDL), high-density lipoprotein (HDL), and triglycerides, overall and among men with dyslipidemia.ResultsHigh cholesterol was associated with increased risk of recurrence in black [HR(per10 mg/dL) 1.06; 95% confidence interval (CI), 1.02-1.11] but not non-black men (HR(per10 mg/dL) 0.99; 95% CI, 0.95-1.03; P(interaction) = 0.011). Elevated triglycerides were associated with increased risk in both black and non-black men (HR(per10 mg/dL) 1.02; 95% CI, 1.00-1.03 and 1.02; 95% CI, 1.00-1.02, respectively; P(interaction) = 0.458). There were no significant associations between LDL or HDL and recurrence risk in either race. Associations with cholesterol, LDL, and triglycerides were similar among men with dyslipidemia, but low HDL was associated with increased risk of recurrence in black, but not non-black men with dyslipidemia (P(interaction) = 0.047).ConclusionElevated cholesterol was a risk factor for recurrence in black but not non-black men, whereas high triglycerides were associated with increased risk regardless of race.ImpactSignificantly contrasting associations by race may provide insight into prostate cancer racial disparities.

ObjectiveTo evaluate performance of pelvic lymph node dissection during radical prostatectomy within an equal access care setting over a period of time, and stratified by prostate cancer risk group and surgical technique.MethodsWe identified men in the Shared Equal Access Regional Cancer Hospital database who had open or robotic-assisted radical prostatectomy from 2006 to 2013. Univariable logistic regression was used to test the association between age, race, body mass index, total biopsy cores, number of positive biopsy cores, risk group, year, center, surgical volume and surgical technique on pelvic lymph node dissection use. Multivariable logistic analysis was used to examine surgical technique and pelvic lymph node dissection performance. Spearman's correlation examined temporal changes in pelvic lymph node dissection utilization stratified by risk group and surgical technique.ResultsA total of 1425 men met inclusion criteria; 67% of them underwent pelvic lymph node dissection. On multivariable analysis, robotic-assisted radical prostatectomy was associated with an 92% decreased use of pelvic lymph node dissection in low-risk, 84% decreased in intermediate-risk and 91% decreased in high-risk men (all P < 0.001). In robotic-assisted radical prostatectomy, there was a trend for increased pelvic lymph node dissection utilization over time in high-risk men (Spearman; P = 0.077) reaching ~85% in 2012-2013, which was accompanied by increased use in low-risk men (P = 0.016). For open radical prostatectomy, fewer pelvic lymph node dissections were carried out in low-risk men over time, decreasing to ~35% (P = 0.047) in 2012-2013, whereas rates remained high for high-risk men throughout (~95%; P = 0.621).ConclusionRegardless of risk group, pelvic lymph node dissection is carried out significantly less during robotic-assisted radical prostatectomy. For robotic-assisted radical prostatectomy, pelvic lymph node dissection utilization increased over time for high-risk men, but rates also increased for low-risk men. Further attention to the discrepancy between provided and guideline recommended pelvic lymph node dissection performance is required to improve prostate cancer care.

ObjectiveTo assess the impact of positive surgical margins (PSMs) on long-term outcomes after radical prostatectomy (RP), including metastasis, castrate-resistant prostate cancer (CRPC), and prostate cancer-specific mortality (PCSM).Patients and methodsRetrospective study of 4,051 men in the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort treated by RP from 1988 to 2013. Proportional hazard models were used to estimate hazard ratios (HRs) of PSMs in predicting biochemical recurrence (BCR), CRPC, metastases, and PCSM. To determine if PSMs were more predictive in certain patients, analyses were stratified by pathological Gleason score, stage, and preoperative prostate-specific antigen (PSA) level.ResultsThe median (interquartile range) follow-up was 6.6 (3.2-10.6) years and 1 127 patients had >10 years of follow-up. During this time, 302 (32%) men had BCR, 112 (3%) developed CRPC, 144 (4%) developed metastases, and 83 (2%) died from prostate cancer. There were 1,600 (40%) men with PSMs. In unadjusted models, PSMs were significantly associated with all adverse outcomes: BCR, CRPC, metastases and PCSM (all P ≤ 0.001). After adjusting for demographic and pathological characteristics, PSMs were associated with increased risk of only BCR (HR 1.98, P < 0.001), and not CRPC, metastases, or PCSM (HR ≤1.29, P > 0.18). Similar results were seen when stratified by pathological Gleason score, stage, or PSA level, and when patients who underwent adjuvant radiotherapy were excluded.ConclusionsPSMs after RP are not an independent risk factor for CRPC, metastasis, or PCSM overall or within any subset. In the absence of other high-risk features, PSMs alone may not be an indication for adjuvant radiotherapy.

BackgroundBenign human prostate tubule-initiating cells (TIC) and aggressive prostate cancer display common traits, including tolerance of low androgen levels, resistance to apoptosis, and microenvironment interactions that drive epithelial budding and outgrowth. TIC can be distinguished from epithelial and stromal cells that comprise prostate tissue via cell sorting based upon Epcam, CD44, and CD49f antigenic profiles. Fetal prostate epithelial cells (FC) possess a similar antigenic profile to adult TIC and are capable of inducing tubule formation. To identify the TIC niche in human prostate tissue, differential keratin (KRT) expression was evaluated.ResultsGene expression data generated from Affymetrix Gene Chip human U133 Plus 2.0 array of sorted adult and fetal epithelial cells revealed KRT13 to be significantly enriched in FC and TIC compared to basal cells (BC) and luminal cells (LC) (p

BackgroundMetastatic lesions in prostate cancer beyond the bone have prognostic importance and affect clinical therapeutic decisions. Few data exist regarding the prevalence of soft-tissue metastases at the initial diagnosis of metastatic castration-resistant prostate cancer (mCRPC).MethodsThis study analyzed 232 men with nonmetastatic (M0) castration-resistant prostate cancer (CRPC) who developed metastases detected by a bone scan or computed tomography (CT). All bone scans and CT scans within the 30 days before or after the mCRPC diagnosis were reviewed. The rate of soft-tissue metastases among those undergoing CT was determined. Then, predictors of soft-tissue metastases and visceral and lymph node metastases were identified.ResultsCompared with men undergoing CT (n = 118), men undergoing only bone scans (n = 114) were more likely to have received primary treatment (P = .048), were older (P = .013), and less recently developed metastases (P = .018). Among those undergoing CT, 52 (44%) had soft-tissue metastases, including 20 visceral metastases (17%) and 41 lymph node metastases (35%), whereas 30% had no bone involvement. In a univariable analysis, only prostate-specific antigen (PSA) predicted soft-tissue metastases (odds ratio [OR], 1.27; P = .047), and no statistically significant predictors of visceral metastases were found. A higher PSA level was associated with an increased risk of lymph node metastases (OR, 1.38; P = .014), whereas receiving primary treatment was associated with decreased risk (OR, 0.36; P = .015).ConclusionsThe data suggest that there is a relatively high rate of soft-tissue metastasis (44%) among CRPC patients undergoing CT at the initial diagnosis of metastases, including some men with no bone involvement. Therefore, forgoing CT during a metastatic evaluation may lead to an underdiagnosis of soft-tissue metastases and an underdiagnosis of metastases in general. Cancer 2015. © 2015 American Cancer Society. Cancer 2016;122:222-229. © 2015 American Cancer Society.

ObjectivesTo assess whether larger tumor volume in black men explains higher presurgical PSA levels versus white men with prostate cancer.MethodsWe retrospectively analyzed 1904 men from the Shared Equal Access Regional Cancer Hospital database who underwent radical prostatectomy from 1990 to 2013. Geometric mean of tumor volume and preoperative PSA for each race were estimated from multivariable linear regression models.ResultsThere were 1104 (58%) white men and 800 (42%) black men. Black men were younger (60.2 vs. 62.9 years, p

BackgroundPrevious studies of prostate cancer (PCa) risk and anthropometrics (ie, body measurements) were based on single measurements or obtained over limited time spans.ObjectiveTo study the association between anthropometrics measured at multiple time points in life and their relation to later diagnosis, metastasis, or death from PCa.Design, setting, and participantsThis case-control study includes 27 167 Swedish men enrolled in two population-based projects from 1974 to 1996. PCa diagnosis up to December 31, 2006, disease information, gestation time, and anthropometrics at birth, military conscript testing, and adulthood were collected. A total of 1355 PCa cases were matched with 5271 controls.Outcome measurements and statistical analysisUnivariate conditional logistic regression was used to determine whether clinical diagnosis, metastasis, or PCa death was associated with low birth weight (weight

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

ObjectiveConcerns about over-treatment have led to practice guidelines discouraging active treatment of prostate cancer (PCa) in men with limited life expectancies and/or low-risk tumors. We evaluated treatment patterns for older veterans with localized PCa, particularly those with low-risk features.MethodsWe used VA Cancer Registry data to identify men aged 65+ diagnosed with clinically localized PCa between January 1st, 2003 and December 31st, 2008. We obtained baseline data on demographics, tumor characteristics, comorbidities, and initial treatment within 6 months of diagnosis: radical prostatectomy, radiotherapy, primary androgen-deprivation therapy (PADT), or no active treatment. National VA surveys provided facility data, including academic affiliation, availability of oncologic specialists, and distance to radiotherapy facilities. Multinomial regression analyses determined associations between patient and facility characteristics and cancer treatment for men with localized (stageResults17,206 veterans had localized PCa, 32% age 75+, 12% had comorbidity scores ≥3, and 33% had low-risk tumors. Overall, 39% received radiotherapy, 6% surgery, 20% PADT, and 35% no active treatment. For those with low-risk cancers, older men (RR=0.36, 95% CI 0.30-0.43) and sicker men (RR=0.75, 95% CI 0.62-0.90) were less likely to receive surgery or radiotherapy versus no active treatment. Over time, more of these men received no active treatment (from 41% to 57%, P

Abstract: INTRODUCTION: At the population level among otherwise “healthy” men, obesity is associated with prostate cancer mortality. However, few studies analyzed the associations between obesity and long-term progression after surgery, such as castration-resistant prostate cancer (CRPC) and prostate cancer-specific mortality (PCSM). We examined the effect of obesity at the time of radical prostatectomy (RP) on long-term prostate cancer-specific outcomes among men treated at Veterans Affairs Hospitals in the USA. METHODS: We combined data from patients undergoing RP at six Veterans Affairs Medical Centers (West Los Angeles, San Diego, and Palo Alto, CA; Augusta, GA; and Durham and Asheville, NC) into the SEARCH database. Our exposure, body mass index (BMI) was abstracted from the medical records at the time of but prior to RP and categorized as normal weight (

ObjectiveTo test the relationship of smoking and aggressive prostate cancer in men undergoing radical prostatectomy.MethodsA retrospective analysis of 2290 men who underwent radical prostatectomy from the Shared Equal Access Regional Cancer Hospital database from 2000 to 2013 was carried out. There were 1592 (70%) non-smokers and 698 (30%) smokers at radical prostatectomy. Logistic regression was used to examine whether smoking predicted Gleason score (≥4 + 3), margin status, extracapsular extension or seminal vesicle invasion. Linear regression was used to test the relationship between smoking and tumor volume.ResultsSmokers were younger, more likely to be black, had lower body mass index, higher pathological Gleason score, more positive margins and extracapsular extension (all P

PurposeTo investigate the association between Agent Orange (AO) exposure and long-term prostate cancer (PC) outcomes.Material and methodsData from 1,882 men undergoing radical prostatectomy for PC between 1988 and 2011 at Veterans Affairs Health Care Facilities were analyzed from the Shared Equal Access Regional Cancer Hospital database. Men were stratified by AO exposure (binary). Associations between AO exposure and biopsy and pathologic Gleason sum (GS) and pathologic stage were determined by logistic regression models adjusted for preoperative characteristics. Hazard ratios for biochemical recurrence (BCR), secondary treatment, metastases, and PC-specific mortality were determined by Cox models adjusted for preoperative characteristics.ResultsThere were 333 (17.7%) men with AO exposure. AO-exposed men were younger (median 59 vs. 62 y), had lower preoperative prostate-specific antigen levels (5.8 vs. 6.7 ng/ml), lower clinical category (25% vs. 38% palpable), and higher body mass index (28.2 vs. 27.6 kg/m(2)), all P

ObjectiveTo test the relationship of smoking and aggressive prostate cancer in men undergoing radical prostatectomy.MethodsA retrospective analysis of 2290 men who underwent radical prostatectomy from the Shared Equal Access Regional Cancer Hospital database from 2000 to 2013 was carried out. There were 1592 (70%) non-smokers and 698 (30%) smokers at radical prostatectomy. Logistic regression was used to examine whether smoking predicted Gleason score (≥4 + 3), margin status, extracapsular extension or seminal vesicle invasion. Linear regression was used to test the relationship between smoking and tumor volume.ResultsSmokers were younger, more likely to be black, had lower body mass index, higher pathological Gleason score, more positive margins and extracapsular extension (all P

BackgroundClinical stage T2c (cT2c) is an indeterminate factor in prostate cancer (PC) risk stratification. According to the D'Amico grouping and American Urological Association guidelines, cT2c is a high risk, whereas the National Comprehensive Cancer Network and the European Urological Association classify cT2c as an intermediate risk. This study assessed whether cT2c tumors without other high-risk factors (clinical stage T2c, not otherwise specified [cT2c-NOS]) behaved as an intermediate or high risk through an analysis of biochemical recurrence (BCR) after radical prostatectomy.MethodsTwo thousand seven hundred fifty-nine men from the Shared Equal Access Regional Cancer Hospital (SEARCH) Database and 12,900 men from Johns Hopkins Hospital (JHH) from 1988-2011 and 1982-2012, respectively, were analyzed. Patients were grouped into low-risk (prostate-specific antigen [PSA] < 10 ng/mL, Gleason sum ≤ 6, and cT1-T2a), intermediate-risk (PSA = 10-20 ng/mL, Gleason sum = 7, or cT2b), and high-risk PC categories (PSA > 20 ng/mL, Gleason sum = 8-10, or cT3). Men with cT2c tumors who were not otherwise at high risk (ie, PSA< 20 ng/mL and Gleason sum < 8) were placed into a separate category termed cT2c-NOS. Associations between cT2c-NOS and intermediate- and high-risk patients and BCR were tested with the log-rank test and Cox proportional analysis models.ResultsNinety-nine men (4%) from SEARCH and 202 men (2%) from JHH had tumors classified as cT2c-NOS. The cT2c-NOS patients had a BCR risk similar to that of the intermediate-risk patients (SEARCH, P = .27; JHH, P = .23) but a significantly lower BCR risk in comparison with the high-risk patients (SEARCH, P < .001; JHH, P < .001). When they were specifically compared with intermediate- and high-risk patients, after adjustments for year and center, cT2c-NOS patients had outcomes comparable to those of intermediate-risk patients (SEARCH, P = .53; JHH, P = .54) but significantly better than those of high-risk patients (SEARCH, P = .003; JHH, P < .001).ConclusionsPatients with cT2c disease without other high-risk features had outcomes similar to the outcomes of patients with intermediate-risk PC and significantly better than the outcomes of patients with high-risk PC. These findings suggest that men with cT2c disease should be considered to be at intermediate risk.

PurposeWe investigated imaging practice patterns in men with nonmetastatic (M0) castration resistant prostate cancer.Materials and methodsWe analyzed data on 247 patients with documented M0 CRPC from the SEARCH database. Patients were selected regardless of primary treatment modality and all had a negative bone scan after a castration resistant prostate cancer diagnosis. Cox models were used to test associations of time to a second imaging test with several demographic and clinical factors.ResultsDuring a median followup of 29.0 months (IQR 12.9-43.5) after a post-castration resistant prostate cancer bone scan was negative, 190 patients (77%) underwent a second imaging test. On univariable analysis patients with higher prostate specific antigen (HR 1.13, p = 0.016), shorter prostate specific antigen doubling time (HR 0.79, p < 0.001) and faster prostate specific antigen velocity (HR 1.01, p < 0.001) were more likely to undergo a second imaging test. Treatment center was also a significant predictor of a second imaging test (p = 0.010). No other factor was a significant predictor. Results were similar on multivariable analysis. It was estimated that approximately 20% of men with a prostate specific antigen doubling time of less than 3 months did not undergo an imaging test in the first year after a post-castration resistant prostate cancer negative bone scan. However, 50% of patients with prostate specific antigen doubling time 15 months or greater underwent a second imaging test in the first year.ConclusionsClinicians use some known predictors of positive imaging tests to determine which patients with M0 castration resistant prostate cancer undergo a second imaging test . However, there may be under imaging in those at high risk and over imaging in those at low risk. Further studies are needed to identify risk factors for metastasis and form clear imaging guidelines in patients with M0 castration resistant prostate cancer.

ObjectivesTo assess the ability of preoperative prostate-specific antigen level, Gleason score and stage to predict prostate cancer outcomes beyond biochemical recurrence, specifically castration-resistant prostate cancer, metastases and prostate cancer-specific mortality in radical prostatectomy patients.MethodsWe carried out a retrospective study of 2735 men in the Shared Equal Access Regional Cancer Hospital database treated by radical prostatectomy from 1988 to 2011 with data available on pathological stage, grade and preoperative prostate-specific antigen. We used Cox hazards analyses to examine the predictive accuracy (c-index) of the preoperative prostate-specific antigen (log-transformed), path Gleason score (≤ 7, 3 + 4, 4 + 3 and 8-10) and path stage grouping (pT2 negative margins; pT2 positive margins; pT3a negative margins; pT3a positive margins; pT3b; vs positive nodes) to predict biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality.ResultsMedian follow up was 8.7 years, during which, 937 (34%) had biochemical recurrence, 108 (4%) castration-resistant prostate cancer, 127 (5%) metastases and 68 (2%) prostate cancer-specific mortality. For the outcomes of biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality, the c-indices were, respectively: prostate-specific antigen 0.65, 0.66, 0.64 and 0.69; Gleason score 0.66, 0.83, 0.76 and 0.85; and pathological stage group 0.69, 0.76, 0.72 and 0.80.ConclusionsGleason score can predict with very high accuracy prostate cancer-specific mortality in patients undergoing radical prostatectomy. Thus, Gleason score should be given more weight in nomograms to predict prostate cancer-specific mortality. Furthermore, men with a high Gleason score should be given special consideration for adjuvant treatment or referral to clinical trials because of a higher risk of prostate cancer-specific mortality.

ObjectivesTo assess the ability of preoperative prostate-specific antigen level, Gleason score and stage to predict prostate cancer outcomes beyond biochemical recurrence, specifically castration-resistant prostate cancer, metastases and prostate cancer-specific mortality in radical prostatectomy patients.MethodsWe carried out a retrospective study of 2735 men in the Shared Equal Access Regional Cancer Hospital database treated by radical prostatectomy from 1988 to 2011 with data available on pathological stage, grade and preoperative prostate-specific antigen. We used Cox hazards analyses to examine the predictive accuracy (c-index) of the preoperative prostate-specific antigen (log-transformed), path Gleason score (≤ 7, 3 + 4, 4 + 3 and 8-10) and path stage grouping (pT2 negative margins; pT2 positive margins; pT3a negative margins; pT3a positive margins; pT3b; vs positive nodes) to predict biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality.ResultsMedian follow up was 8.7 years, during which, 937 (34%) had biochemical recurrence, 108 (4%) castration-resistant prostate cancer, 127 (5%) metastases and 68 (2%) prostate cancer-specific mortality. For the outcomes of biochemical recurrence, castration-resistant prostate cancer, metastases and prostate cancer-specific mortality, the c-indices were, respectively: prostate-specific antigen 0.65, 0.66, 0.64 and 0.69; Gleason score 0.66, 0.83, 0.76 and 0.85; and pathological stage group 0.69, 0.76, 0.72 and 0.80.ConclusionsGleason score can predict with very high accuracy prostate cancer-specific mortality in patients undergoing radical prostatectomy. Thus, Gleason score should be given more weight in nomograms to predict prostate cancer-specific mortality. Furthermore, men with a high Gleason score should be given special consideration for adjuvant treatment or referral to clinical trials because of a higher risk of prostate cancer-specific mortality.

73 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

ObjectiveTo investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP.Patients and methodsWe conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men.ResultsAfter adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384).ConclusionIn this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.

ObjectiveTo investigate how statin use is associated with the probability of having an abnormal screening prostate-specific antigen (PSA) result according to common PSA thresholds for biopsy (>2.5, >4.0, and >6.5 ng/mL).MethodsWe conducted a cross-sectional study of 323,426 men aged ≥65 years who had a screening PSA test in 2003 at a Veterans Affairs facility. The primary predictor was the use of statin medications at the time of index screening PSA test. The main outcome was the screening PSA value. Poisson regressions were performed to calculate adjusted relative risks for having an abnormal screening PSA result according to statin usage.ResultsPercentages of men with PSA results exceeding commonly used thresholds of >2.5, >4.0, and >6.5 ng/mL were 21.0%, 7.6%, and 1.6%, respectively. These percentages decreased with statin use, increasing statin dose, duration of statin use, and potency of the statin. For example, after adjusting for age, the percentage of men having a PSA level >4.0 ng/mL ranged from 8.2% in non-statin users to 6.2% in men prescribed with >40 mg of simvastatin dose. Adjusted relative risks of having a PSA level >4.0 ng/mL were 0.89 (95% confidence interval [CI], 0.86-0.93), 0.87 (95% CI, 0.84-0.91), and 0.83 (95% CI, 0.80-0.87), respectively for men on simvastatin dose of 5-20, >20-40, and >40 mg vs non-statin users.ConclusionStatin use is associated with a reduction in the probability that an older man will have an abnormal screening PSA result, regardless of the PSA threshold. This reduction is more pronounced with higher statin dose, longer statin duration, and higher statin potency.

BackgroundEvidence for an association between total cholesterol, low- and high-density lipoproteins (LDL and HDL, respectively), triglycerides, and prostate cancer is conflicting. Given that prostate cancer and dyslipidemia affect large proportions of Western society, understanding these associations has public health importance.MethodsWe conducted a retrospective cohort analysis of 843 radical prostatectomy (RP) patients who never used statins before surgery within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analysis was used to investigate the association between cholesterol, LDL, HDL, and triglycerides and biochemical recurrence risk. In secondary analysis, we explored these associations in patients with dyslipidemia, defined using National Cholesterol Education Program guidelines.ResultsElevated serum triglycerides were associated with increased risk of prostate cancer recurrence [HRper 10 mg/dl, 1.03; 95% confidence interval (CI), 1.01-1.05] but associations between total cholesterol, LDL and HDL, and recurrence risk were null. However, among men with dyslipidemia, each 10 mg/dl increase in cholesterol and HDL was associated with 9% increased recurrence risk (HR, 1.09; 95% CI, 1.01-1.17) and 39% reduced recurrence risk (HR, 0.61; 95% CI, 0.41-0.91), respectively.ConclusionsElevated serum triglycerides were associated with increased risk of prostate cancer recurrence. Cholesterol, LDL, or HDL were not associated with recurrence risk among all men. However, among men with dyslipidemia, elevated cholesterol and HDL levels were associated with increased and decreased risk of recurrence, respectively.ImpactThese findings, coupled with evidence that statin use is associated with reduced recurrence risk, suggest that lipid levels should be explored as a modifiable risk factor for prostate cancer recurrence.

ObjectiveTo investigate the effect of statin use after radical prostatectomy (RP) on biochemical recurrence (BCR) in patients with prostate cancer who never received statins before RP.Patients and methodsWe conducted a retrospective analysis of 1146 RP patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Multivariable Cox proportional hazards analyses were used to examine differences in risk of BCR between post-RP statin users vs nonusers. To account for varying start dates and duration of statin use during follow-up, post-RP statin use was treated as a time-dependent variable. In a secondary analysis, models were stratified by race to examine the association of post-RP statin use with BCR among black and non-black men.ResultsAfter adjusting for clinical and pathological characteristics, post-RP statin use was significantly associated with 36% reduced risk of BCR (hazard ratio [HR] 0.64, 95% confidence interval [CI] 0.47-0.87; P = 0.004). Post-RP statin use remained associated with reduced risk of BCR after adjusting for preoperative serum cholesterol levels. In secondary analysis, after stratification by race, this protective association was significant in non-black (HR 0.49, 95% CI 0.32-0.75; P = 0.001) but not black men (HR 0.82, 95% CI 0.53-1.28; P = 0.384).ConclusionIn this retrospective cohort of men undergoing RP, post-RP statin use was significantly associated with reduced risk of BCR. Whether the association between post-RP statin use and BCR differs by race requires further study. Given these findings, coupled with other studies suggesting that statins may reduce risk of advanced prostate cancer, randomised controlled trials are warranted to formally test the hypothesis that statins slow prostate cancer progression.

BackgroundIn the prostate-specific antigen (PSA) screening era, approximately 15% of US men still present with clinically high-risk prostate cancer (PC). However, high-risk PC may be downgraded/downstaged at radical prostatectomy (RP), making additional therapy unnecessary. The authors tested the oncologic outcomes in men with clinically high-risk disease stratified on RP pathology.MethodsA total of 611 men with high-risk PC (PSA level > 20 ng/mL, biopsy Gleason sum [bGS] ≥ 8, or clinical classification of ≥ T3) underwent RP and pelvic lymphadenectomy between 1998 and 2011. Outcomes included biochemical disease recurrence (BCR), receipt of androgen deprivation therapy (ADT), metastases, and PC-specific and overall survival. RP pathology was classified as unfavorable (pathologic Gleason sum ≥ 8, pathologic classification of ≥ T3, or lymph node-positive disease), or favorable (no unfavorable features). Multivariable analyses tested oncologic outcomes stratified by pathologic classification.ResultsOverall, 527 men had complete pathologic data and were included in the current analysis. Of the cohort, 206 of 527 men (39%) had favorable pathology. This finding was more common in men with only 1 clinical high-risk feature, and a lower body mass index, PSA level, bGS, and percentage positive biopsy cores. Favorable pathology was associated with decreased BCR (hazards ratio [HR], 0.34), metastases (HR, 0.17), and PC death (HR, 0.17). After a median follow-up of 82 months (range, 49 months-131 months), 193 of the 527 men (37%) received ADT, including only 35 of the 206 men with favorable pathology (17%). Unfavorable pathology was associated with early (≤ 5 years) but not late treatment with ADT.ConclusionsIn a large cohort of men with high-risk PC who were managed with RP, 39% had favorable pathology and superior oncologic outcomes.

BackgroundThe University of California, San Francisco, Cancer of the Prostate Risk Assessment Postsurgical (CAPRA-S) score uses pathologic data from radical prostatectomy (RP) to predict prostate cancer recurrence and mortality. However, this clinical tool has never been validated externally.ObjectiveTo validate CAPRA-S in a large, multi-institutional, external database.Design, setting, and participantsThe Shared Equal Access Regional Cancer Hospital (SEARCH) database consists of 2892 men who underwent RP from 2001 to 2011. With a median follow-up of 58 mo, 2670 men (92%) had complete data to calculate a CAPRA-S score.InterventionRP.Outcome measurements and statistical analysisThe main outcome was biochemical recurrence. Performance of CAPRA-S in detecting recurrence was assessed and compared with a validated postoperative nomogram by concordance index (c-index), calibration plots, and decision curve analysis. Prediction of cancer-specific mortality was assessed by Kaplan-Meier analysis and the c-index.Results and limitationsThe mean age was 62 yr (standard deviation: 6.3), and 34.3% of men had recurrence. The 5-yr progression-free probability for those patients with a CAPRA-S score of 0-2, 3-5, and 6-10 (defining low, intermediate, and high risk) was 72%, 39%, and 17%, respectively. The CAPRA-S c-index was 0.73 in this validation set, compared with a c-index of 0.72 for the Stephenson nomogram. Although CAPRA-S was optimistic in predicting the likelihood of being free of recurrence at 5 yr, it outperformed the Stephenson nomogram on both calibration plots and decision curve analysis. The c-index for predicting cancer-specific mortality was 0.85, with the caveat that this number is based on only 61 events.ConclusionsIn this external validation, the CAPRA-S score predicted recurrence and mortality after RP with a c-index >0.70. The score is an effective prognostic tool that may aid in determining the need for adjuvant therapy.

UnlabelledErectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n=25 per group) after RP. AT consisted of five walking sessions per week at 55-100% of peak oxygen uptake (VO2peak) for 30-60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow-mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤ 21) decreased by 20% in the AT group and by 24% in the UC group (difference: p=0.406). There were no significant between-group differences in any erectile function subscale (p>0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP.Trial registrationClinicaltrials.gov identifier NCT00620932.