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BackgroundAlthough skeletal-related events (SREs) are linked with a reduced quality of life and worse outcomes, to the authors' knowledge the factors that predict SREs are minimally understood. The objective of the current study was to identify predictors of SREs and all-cause mortality among men with metastatic castration-resistant prostate cancer (mCRPC).MethodsData were collected on 837 men with bone mCRPC at 8 Veterans Affairs medical centers within the Shared Equal Access Regional Cancer Hospital (SEARCH) database from 2000 through 2017. Patients were followed to assess development of SREs (pathological fracture, radiotherapy to bone, spinal cord compression, or surgery to bone). Cox proportional hazards models were used to evaluate predictors of SREs and mortality.ResultsOf the 837 men with bone mCRPC, 287 developed a SRE and 740 men died (median follow-up, 26 months). Bone pain was found to be the strongest predictor of SREs (hazard ratio [HR], 2.96; 95% CI, 2.25-3.89). A shorter time from CRPC to the development of metastasis (HR, 0.92; 95% CI, 0.85-0.99), shorter progression to CRPC (HR, 0.94; 95% CI, 0.91-0.98), and visceral metastasis at the time of diagnosis of bone metastasis (HR, 1.91; 95% CI, 1.18-3.09) were associated with an increased risk of SREs. Ten or more bone metastases (HR, 2.17; 95% CI, 1.72-2.74), undergoing radical prostatectomy (HR, 0.73; 95% CI, 0.61-0.89), shorter progression to CRPC (HR, 0.97; 95% CI, 0.94-0.99), older age (HR, 1.03; 95% CI, 1.02-1.04), higher prostate-specific antigen level at the time of diagnosis of metastasis (HR, 1.21; 95% CI, 1.14-1.28), bone pain (HR, 1.44; 95% CI, 1.23-1.70), and visceral metastasis (HR, 1.72; 95% CI, 1.23-2.39) were associated with an increased mortality risk.ConclusionsAmong men with bone mCRPC, bone pain was found to be the strongest predictor of SREs and the number of bone metastases was a strong predictor of mortality. If validated, these factors potentially may be used for risk stratification and for SRE prevention strategies.

BackgroundAlthough diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP).MethodsThe authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only.ResultsA total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value

BackgroundIn this study among men who underwent radical prostatectomy (RP), African American men (AAM) were 28% more likely to develop recurrent disease compared with Caucasian men (CM). However, among those who had nonmetastatic, castration-resistant prostate cancer (CRPC), race did not predict metastases or overall survival. Whether race predicts metastases among men who receive androgen-deprivation therapy (ADT) after a biochemical recurrence (BCR) (ie, before CRPC but after BCR) is untested.MethodsThe authors identified 595 AAM and CM who received ADT for a BCR that developed after RP between 1988 and 2015 in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database. Univariable and multivariable Cox models were used to test the association between race and the time from ADT to metastases. Secondary outcomes included the time to CRPC, all-cause mortality, and prostate cancer-specific mortality.ResultsDuring a median follow-up of 66 months after ADT, 62 of 354 CM (18%) and 38 of 241 AAM (16%) developed metastases. AAM were younger at the time they received ADT (63 vs 67 years; P < .001), had received ADT in a more recent year (2008 vs 2006; P < .001), had higher prostate-specific antigen levels at RP (11.1 vs 9.2 ng/mL; P < .001), lower pathologic Gleason scores (P = .004), and less extracapsular extension (38% vs 48%; P = .022). On multivariable analysis, there was no association between race and metastases (hazard radio, 1.20; P = .45) or any of the other secondary outcomes (all P > .5).ConclusionsAmong veterans who received ADT post-BCR after RP, race was not a predictor of metastases or other adverse outcomes. The current findings suggest that research efforts to understand racial differences in prostate cancer biology should focus on early stages of the disease (ie, closer to the time of diagnosis).

BackgroundA 5-tier prognostic grade group (GG) system was enacted to simplify the risk stratification of patients with prostate cancer in which Gleason scores of ≤6, 3 + 4, 4 + 3, 8, and 9 or 10 are considered GG 1 through 5, respectively. The authors investigated the utility of biopsy GG for predicting long-term oncologic outcomes after radical prostatectomy in an equal-access health system.MethodsMen who underwent prostatectomy at 1 of 6 Veterans Affairs hospitals in the Shared Equal Access Regional Cancer Hospital database between 2005 and 2015 were reviewed. The prognostic ability of biopsy GG was examined using Cox models. Interactions between GG and race also were tested.ResultsIn total, 2509 men were identified who had data available on biopsy Gleason scores, covariates, and follow-up. The cohort included men with GG 1 (909 patients; 36.2%), GG 2 (813 patients; 32.4%), GG 3 (398 patients; 15.9%), GG 4 (279 patients; 11.1%), and GG 5 (110 patients; 4.4%) prostate cancer. The cohort included 1002 African American men (41%). The median follow-up was 60 months (interquartile range, 33-90 months). Higher GG was associated with higher clinical stage, older age, more recent surgery, and surgical center (P < .001) as well as increased biochemical recurrence, secondary therapy, castration-resistant prostate cancer, metastases, and prostate cancer-specific mortality (all P < .001). There were no significant interactions with race in predicting measured outcomes.ConclusionsThe 5-tier GG system predicted multiple long-term endpoints after radical prostatectomy in an equal-access health system. The predictive value was consistent across races. Cancer 2017;123:4122-4129. © 2017 American Cancer Society.

BackgroundBlack race is associated with prostate cancer (PC) diagnosis and poor outcome. Previously, the authors reported that black men undergoing radical prostatectomy (RP) in equal-access hospitals had an increased risk of biochemical disease recurrence (BCR), but recurrences were equally aggressive as those occurring in white men. The authors examined the association between race and long-term outcomes after RP.MethodsData regarding 1665 black men (37%) and 2791 white men (63%) undergoing RP were analyzed. Using Cox models, the authors tested the association between race and BCR, BCR with a prostate-specific antigen (PSA) doubling time

BackgroundSkeletal-related events (SREs) are common complications of bone metastatic castration-resistant prostate cancer (mCRPC). To the authors' knowledge, there are limited data regarding which factors predict SREs. The authors identified risk factors for SREs in men with bone mCRPC using characteristics commonly available in the medical record.MethodsData from 454 patients with nonmetastatic CRPC were identified from 2 Veteran Affairs Medical Centers from 2000 through 2013. Among these men, 233 (51%) developed bone metastases during follow-up and represented the study cohort. First occurrence of an SRE was abstracted from the medical records. A stepwise multivariable Cox model was used to select the strongest predictors of time to SRE.ResultsThe median age of the patients at the time of diagnosis of bone mCRPC was 75 years (interquartile range, 68-81 years), and there were 153 nonblack patients (66%). During follow-up (median, 7.8 months [interquartile range, 2.9-18.3 months]), 88 patients (38%) had an SRE. On univariable analysis, more recent year of metastasis (hazard ratio [HR], 0.91), prostate-specific antigen doubling time of ≥9 months versus

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.

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.

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 current study was conducted to analyze the association between cigarette smoking and metastasis (the primary outcome) as well as time to biochemical disease recurrence (BCR), metastasis, castration-resistant prostate cancer (CRPC), and prostate cancer-specific and overall mortality (secondary outcomes) after radical prostatectomy among men from the Shared Equal Access Regional Cancer Hospital cohort.MethodsA retrospective analysis was performed of 1450 subjects for whom smoking status was available from preoperative notes. Analysis of baseline characteristics by smoking status was performed using the chi-square and rank sum tests. The association between smoking status and time to the event was analyzed using Kaplan-Meier plots, the log-rank test, and Cox and competing risk models.ResultsA total of 549 men (33%) men were active smokers and 1121 (67%) were nonsmokers at the time of surgery. Current smokers were younger and had a lower body mass index, higher prostate-specific antigen level, and more extracapsular extension and seminal vesicle invasion (all P

BackgroundThe University of California, San Francisco (UCSF) Cancer of the Prostate Risk Assessment (CAPRA) is a novel preoperative index which predicts the risk of biochemical recurrence after radical prostatectomy. The performance of the index is at least as good as the best available instruments based on clinical variables, and the 0 to 10 score is simple to calculate for both clinical and research purposes. This study used a large external dataset to validate CAPRA.MethodsData were abstracted from the Shared Equal Access Regional Cancer Hospital (SEARCH) database, a registry of men who underwent radical prostatectomy at 4 Veterans Affairs and 1 active military medical center. Of 2096 men in the database, 1346 (64%) had full data available to calculate the CAPRA score. Performance of the CAPRA score was assessed with proportional hazards regression, survival analysis, and the concordance (c) index.ResultsOf the studied patients, 41% were non-Caucasian, and their mean age was 62 years. Twenty-six percent suffered recurrence; median follow-up among patients who did not recur was 34 months. The hazard ratio (HR) for each 1-point increase in CAPRA was 1.39 (95% CI [confidence interval], 1.31-1.46). The 5-year recurrence-free survival rate ranged from 86% for CAPRA 0-1 patients to 21% for CAPRA 7-10 patients. Increasing CAPRA scores were significantly associated with increasing risk of adverse pathologic outcomes. The c-index for CAPRA for the validation set was 0.68, compared with 0.66 for the original development set.ConclusionsThe UCSF-CAPRA accurately predicted both biochemical and pathologic outcomes after radical prostatectomy among a large, diverse, cohort of men. These results validated the effectiveness of this powerful and straightforward instrument.

Background: This study was conducted to better characterize the epidemiology, clinical outcomes, and current treatment patterns of de novo oligometastatic hormone-sensitive prostate cancer (omHSPC) in the United States Veterans Affairs Health Care System., Methods: In this observational retrospective cohort study, 400 de novo metastatic hormone-sensitive PC (mHSPC) patients diagnosed from January 2015 to December 2020 (follow-up through December 2021) were randomly selected. omHSPC was defined as five or less total metastases (excluding liver) by conventional imaging. Kaplan-Meier methods estimated overall survival (OS) and castration-resistant prostate cancer (CRPC)-free survival from mHSPC diagnosis date and a log-rank test compared these outcomes by oligometastatic status., Results: Twenty percent (79 of 400) of de novo mHSPC patients were oligometastatic. Most baseline characteristics were similar by oligometastatic status; however, men with non-omHSPC had higher median prostate-specific antigen at diagnosis (151.7) than omHSPC (44.1). First-line (1L) novel hormonal therapy was similar between groups (20%); 1L chemotherapy was lower in omHSPC (5%) versus non-omHSPC (14%). More omHSPC patients received metastasis-directed therapy/prostate radiation therapy (14%) versus non-omHSPC (2%). Median OS and CRPC-free survival (in months) were higher in omHSPC versus non-omHSPC (44.4; 95% confidence interval [CI], 33.9-not estimated vs. 26.2; 95% CI, 20.5-32.5, p = .0089 and 27.6; 95% CI, 22.1-37.2 vs. 15.3; 95% CI, 12.8-17.9, p = .0049), respectively., Conclusions: Approximately 20% of de novo mHSPC were oligometastatic, and OS was significantly longer in omHSPC versus non-omHSPC. Although potentially "curative" therapy use was higher in omHSPC versus non-omHSPC, the percentages were still relatively low. Future studies are warranted given potential for prolonged responses with multimodal therapy inclusive of systemic and local therapies., (© 2024 American Cancer Society.)

Purpose: Prior studies testing the association between insulin resistance (IR) and prostate cancer (PC) risk are inconsistent. We examined the association between Homeostatic Assessment of Insulin Resistance (HOMA-IR; calculated from fasting baseline insulin and glucose) and PC in REDUCE, a 4-year randomized trial of dutasteride vs. placebo for PC prevention., Experimental Design: All patients had prestudy negative biopsies and underwent study mandated biopsies at 2 and 4 years regardless of prostate-specific antigen. Multivariable logistic regression models were used to investigate the associations between log-transformed or categorized HOMA-IR scores and PC risk. Multinominal regression was used to assess associations between HOMA-IR scores and tumor grade (low grade [grade group 1]; high-grade [grade groups 2-5])., Results: Among 5430 REDUCE participants (1212 with PC; 856 low- and 356 high-grade), higher HOMA-IR was associated with lower PC risk (log-HOMA-IR: OR, 0.89; 95% CI, 0.80-0.99; p = .03; categorized HOMA-IR: p-trend = .04). When stratified by grade, HOMA-IR was significantly associated with reduced low-grade PC risk (log-HOMA-IR: OR, 0.84; 95% CI , 0.74-0.94; p = .003; categorized HOMA-IR: p-trend = .002) but was unrelated to high-grade PC (log-HOMA-IR: OR, 1.02; 95% CI, 0.86-1.21; p = .81; categorized HOMA-IR: p-trend = .26). Results were similar in placebo and treatment arms., Conclusions: In summary, higher HOMA-IR was associated with a reduced risk of low-grade PC but was not associated with high-grade disease. The mechanisms to explain these findings are unclear., (© 2024 American Cancer Society.)

Prostate cancer is the most common malignancy among men worldwide, and androgen-deprivation therapy (ADT) is a mainstay of treatment. There are observational data demonstrating an increased risk of cardiovascular events in patients who receive ADT, particularly those who have an elevated baseline cardiovascular risk. Because, for most patients with prostate cancer, death is predominantly from noncancer-related causes, cardiovascular disease and its risk factors should be optimized during cancer treatment. This review provides an overview of the landscape of ADT treatment and serves as a guide for appropriate cardiovascular screening and risk-mitigation strategies. The authors emphasize the importance of shared communication between the multidisciplinary cancer team and primary care to improve baseline cardiovascular screening and treatment of modifiable risk factors within this higher risk population., (© 2024 American Cancer Society.)