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Objective: To describe patient characteristics and pathological stage at bladder cancer (BCa) diagnosis in a diverse population within a national, equal‐access healthcare system. Methods: This retrospective cohort study identified 15 966 men diagnosed with BCa in the Veterans Affairs (VA) healthcare system from 2000 to 2020. The primary outcome was pathological stage at diagnosis, determined by index transurethral resection of bladder tumour. Logistic regression was used to assess the relationship between race and stage. Competing risk models tested the association between race and BCa‐specific mortality with cumulative incidence estimates. Results: Of 15 966 BCa patients, 12 868 (81%), 1726 (11%), 493 (3%) and 879 (6%) were White, Black, Hispanic and Other race, respectively. Black patients had significantly higher muscle‐invasive bladder cancer (MIBC) rates than White patients (35% vs 32%; P = 0.009). In multivariable analysis, the odds of presenting with MIBC did not differ significantly between Black and White patients (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.98–1.22) or between Hispanic patients (OR 0.82, 95% CI 0.67–1.01) and White patients. Compared to White patients, Black patients had a similar risk of BCa‐specific mortality (hazard ratio [HR] 0.89, 95% CI 0.75–1.06), whereas Hispanic patients had a lower risk (HR 0.56, 95% CI 0.38–0.82). Conclusions: Black patients presented with the highest rates of de novo MIBC. However, in a large, equal‐access healthcare system, this did not result in a difference in BCa‐specific mortality. In contrast, Hispanic patients had lower risks of MIBC and BCa‐specific mortality. [ABSTRACT FROM AUTHOR]

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. The management of cardiovascular risk factors is significantly underperformed and under‐emphasized for patients with prostate cancer. By using the latest clinical evidence, the authors provide an easy‐to‐use guide for primary care providers and patients' multidisciplinary cancer treatment teams to appropriately address modifiable cardiovascular disease risk factors in this high‐risk population. [ABSTRACT FROM AUTHOR]

Background: We previously reported that outcomes after radical prostatectomy (RP) were similar among non‐Hispanic Black, non‐Hispanic White, and Hispanic White Veterans Affairs (VA) patients. However, prostate cancer (PC) mortality in Puerto Rican Hispanics (PRH) may be higher than in other Hispanic groups. Data focused on PRH patients is sparse; thus, we tested the association between PR ethnicity and outcomes after RP. Methods: Analysis included men in SEARCH cohort who underwent RP (1988–2020, n = 8311). PRH patients (n = 642) were treated at the PR VA, and outcomes were compared to patients treated in the Continental US regardless of race. Logistic regression was used to test the associations between PRH and PC aggressiveness, adjusting for demographic and clinicopathological features. Multivariable Cox models were used to investigate PRH versus Continental differences in biochemical recurrence (BCR), metastases, castration‐resistant PC (CRPC), and PC‐specific mortality (PCSM). Results: Compared to Continental patients, PRH patients had lower adjusted odds of pathological grade group ≥2 (p < 0.001), lymph node metastasis (p < 0.001), and positive margins (p < 0.001). In contrast, PRH patients had higher odds of extracapsular extension (p < 0.001). In Cox models, PRH patients had a higher risk for BCR (HR = 1.27, p < 0.001), metastases (HR = 1.49, p = 0.014), CRPC (HR = 1.80, p = 0.001), and PCSM (HR = 1.74, p = 0.011). Further adjustment for extracapsular extension and other pathological variables strengthened these findings. Conclusions: In an equal access setting, PRH RP patients generally had better pathological features, but despite this, they had significantly worse post‐treatment outcomes than men from the Continental US, regardless of race. The reasons for the poorer prognosis among PRH men require further research. [ABSTRACT FROM AUTHOR]

Purpose: Limited data exist to help surgeons decide between active surveillance (AS) versus treatment for men with favorable intermediate risk (FIR) prostate cancer. To estimate the theoretical excess risk of prostate cancer‐specific mortality (PCSM) with AS versus radical prostatectomy (RP), we determined the risk of PCSM in FIR men undergoing RP and modeled the PCSM risk for AS using a range of increased PSCM scenarios ranging from 1.25x to 2x higher relative to RP. Materials and Methods: We retrospectively reviewed data from men undergoing RP from 1988 to 2017 at 8 Veterans Affairs hospitals within the SEARCH cohort. Men with FIR PC were identified using the NCCN risk criteria. Risk of PCSM at 5, 10, and 15 years after RP was estimated. Using these estimates, PCSM was then modeled for AS using a range of increased risk of PCSM relative to RP ranging from 1.25x to 2x higher. Results: For the 920 FIR men identified, 5‐, 10‐, and 15‐year survival estimates for PCSM after RP were 99.9%, 99.0%, and 97.8%, respectively. If the risk of PCSM on AS were 1.25–2x greater than RP, there would be 0.54%–2.17% excess risk of PCSM at 15 years. Conclusions: The risk of death for FIR after RP is very low. Assuming even modestly increased PCSM with AS versus RP, the excess risk of death for AS in FIR is low even up to 15 years. These data support the consideration of AS as a relatively safe alternative to RP in FIR men, though prospective randomized trials are needed to validate these findings. [ABSTRACT FROM AUTHOR]

The success of the PROfound, IPATential150, and TheraP trials promoted the transition from sequential treatment to therapeutic targets (TTs)‐guided precision treatment in metastatic castration‐resistant prostate cancer (mCRPC). The objective of this study was to evaluate the prevalence and prognostic value of TTs from these three trials. All included Chinese mCRPC patients underwent circulating tumor DNA (ctDNA) sequencing, PTEN status assessment, and dual‐tracer [68Ga‐prostate‐specific membrane antigen (PSMA) and 18F‐fluorodexyglucose (FDG)] positron emission tomography/computed tomography (PET/CT). Previous treatment with cabazitaxel, Lu‐PSMA or olaparib was unallowed. Patients with known significant sarcomatoid or spindle cell or neuroendocrine small cell components were also excluded. TTs were defined as positive as follows: (a) high PSMA and no PSMA−/FDG+ disease on dual‐tracer PET/CT scans; (b) defects in homologous recombination repair (HRR) genes in ctDNA; and (c) loss of PTEN immunohistochemistry staining in tumor tissue. The prevalence and prognostic value on progression‐free survival (PFS) of TTs were evaluated. A total of 106 consecutive mCRPC patients were included. The prevalence of positive PET/CT, HRR defect, and PTEN loss was 30%, 29% and 16%, respectively. Sixty‐three patients had at least one TT. Metastatic volume (odds ratio = 5.0; P = 0.017) was the only independent factor of positive TT in multivariate analysis. Seventy‐four patients received abiraterone after TT screening. Patients with positive PET/CT (P = 0.011) and HRR defect (P = 0.002) had a significantly shorter PFS after receiving abiraterone than patients with negative TTs. However, PTEN status was unrelated to PFS, which may be due to a less number of patients with PTEN loss (P = 0.952). Overall, patients with any positive TTs had a significantly shorter PFS after abiraterone than patients with negative TTs (P = 0.009). Nearly 60% of Chinese patients with mCRPC who had a poor prognosis on abiraterone were candidates for precision treatments based on the specific criteria of TTs. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the hypothesis that there is an improvement in sexual function following smoking cessation (as smoking is a well‐established risk factor for sexual dysfunction), we analysed the association between cigarette smoking and smoking cessation with sexual function among participants of the REduction by DUtasteride of prostate Cancer Events (REDUCE) study. Subjects and Methods: We analysed baseline data of 6754 men, aged 50–75 years divided into: lifelong non‐smokers, former smokers, and current smokers. We examined total testosterone (TT, normal range ≥10 nmol/L) and sexual function variables: self‐reported sexual activity, low libido, and erectile dysfunction (ED). Differences between current vs non‐smokers and former vs current smokers were analysed using the chi‐square test, linear and logistic regressions. Results: A total of 3069 (45.4%) men were non‐smokers, 2673 (39.6%) former smokers, and 1012 (15%) current smokers. Current smokers were significantly younger than former and non‐smokers (mean age 61.6, 63.2, and 62.7 years, respectively), leaner (mean body mass index 27.0, 27.7, and 27.2 kg/m2, respectively), and had less hypertension (32.4%, 41.6%, and 36.8%, respectively; all P < 0.01). In uni‐ and multivariable analysis, current smokers had higher mean TT than non‐smokers (485.4 vs 451.2 nmol/L, P < 0.001), higher prevalence of low libido (25.6% vs 21.0%, P = 0.002) and ED (31.6% vs 26.0%, P < 0.001) with comparable sexual activity (81.7% vs 82.8%, P = 0.420). In multivariable analysis, former smokers had statistically significantly less prevalence of low libido (odds ratio [OR] 0.8, P = 0.013) and ED (OR 0.8, P = 0.006) compared to current smokers. Conclusion: Cigarette smoking was associated with worse sexual health compared to non‐smokers, while former smokers had better erectile function and libido than current smokers. Smoking cessation may improve male sexual health and counselling on smoking cessation may be considered at the time of sexual health evaluations. [ABSTRACT FROM AUTHOR]

Background: The optimal upfront treatment modality for patients with nonmetastatic Gleason Score 9 and 10 prostate cancer (GS 9–10 PCa) is unknown. Methods: We conducted a retrospective cohort study of patients in the Veterans Health Administration (VHA) with GS 9–10 PCa treated with radical prostatectomy (RP) or external beam radiation therapy with androgen deprivation therapy (EBRT+ADT) from 1/2000 to 12/2010. Outcomes included overall survival (OS), distant metastasis‐free survival (DMFS), and salvage/adjuvant therapy‐free survival (SAFS), as assessed by Kaplan–Meier analysis. Results: We identified 1220 veterans with GS 9–10 PCa; 335 were treated with RP, and 885 were treated with EBRT+ADT. With a median follow‐up of 9.9 years, propensity score‐matched analyses demonstrated that RP had superior 10‐year OS (70.8% [RP] vs. 61.2% [EBRT+ADT], p < 0.001), 10‐year DMFS rates were similar between RP (76.7%) and EBRT+ADT (81.0%), and 10‐year SAFS rates were lower for RP vs EBRT + ADT (35.2% [RP] vs. 75.2% [EBRT+ADT], p < 0.001). The receipt of salvage ADT was higher with upfront RP (51.9% vs. 26.1%, p < 0.001), despite receipt of adjuvant/salvage EBRT in 41.8% of RP patients. Among patients treated with RP, there were no differences in outcomes by race. However, higher survival rates were noted among Black patients treated with EBRT+ADT compared with White patients. Conclusions: This analysis demonstrated higher 10‐year OS rates among men treated with upfront RP versus EBRT+ADT, though missing confounders and similar DMFS rates suggest the long‐term cause‐specific OS rates may be similar. We also highlight real‐world outcomes of a diverse patient population in the VHA and improved outcomes for Black patients receiving EBRT+ADT. [ABSTRACT FROM AUTHOR]

Objective: To describe prescription prevalence of oral bladder pain medications among women with interstitial cystitis/bladder pain syndrome (IC/BPS) and to compare with current treatment guidelines. Methods: We sampled female patients with an ICD‐9/10 diagnosis of IC/BPS (595.1/N30.10) by querying active users of the Veterans Health Administration. Medical records were reviewed to determine whether patients met IC/BPS diagnostic criteria. A cohort of women with other pelvic pain disorders was identified. Prescription prevalence of typical non‐narcotic oral bladder pain medications was compared between the two groups and healthy controls. Prescription prevalence was also compared before and after the diagnosis of IC/BPS was made using Poisson regression. Results: There were 641 women who met criteria for IC/BPS and 197 women with "Other pelvic pain" disorders. Women with IC/BPS were prescribed a pain medication more often than those with "Other pelvic pain" (77% vs. 59%, p < 0.0001). Of the women with IC/BPS, 44% tried three or more pain medications. Of women with a diagnosis of IC/BPS, only 67% were prescribed an American Urological Association‐recommended medication. Prescription prevalence increased after diagnosis for both pentosan polysulfate (10%–29%, p < 0.0001) and hydroxyzine (17%–40%, p < 0.0001), but not for amitriptyline or cimetidine. Amitriptyline was prescribed to 223 women with IC/BPS, only 125 of which (56%) had a documented history of depression. Conclusions: Many women with IC/BPS required multiple bladder prescriptions, highlighting the difficulty in finding an effective treatment for IC/BPS. Pentosan polysulfate and hydroxyzine were preferred IC/BPS medications. Our next step will be to analyze treatment patterns in those patients who did not receive medications. [ABSTRACT FROM AUTHOR]

A large proportion of heritability for prostate cancer risk remains unknown. Transcriptome‐wide association study combined with validation comparing overall levels will help to identify candidate genes potentially playing a role in prostate cancer development. Using data from the Genotype‐Tissue Expression Project, we built genetic models to predict normal prostate tissue gene expression using the statistical framework PrediXcan, a modified version of the unified test for molecular signatures and Joint‐Tissue Imputation. We applied these prediction models to the genetic data of 79 194 prostate cancer cases and 61 112 controls to investigate the associations of genetically determined gene expression with prostate cancer risk. Focusing on associated genes, we compared their expression in prostate tumor vs normal prostate tissue, compared methylation of CpG sites located at these loci in prostate tumor vs normal tissue, and assessed the correlations between the differentiated genes' expression and the methylation of corresponding CpG sites, by analyzing The Cancer Genome Atlas (TCGA) data. We identified 573 genes showing an association with prostate cancer risk at a false discovery rate (FDR) ≤ 0.05, including 451 novel genes and 122 previously reported genes. Of the 573 genes, 152 showed differential expression in prostate tumor vs normal tissue samples. At loci of 57 genes, 151 CpG sites showed differential methylation in prostate tumor vs normal tissue samples. Of these, 20 CpG sites were correlated with expression of 11 corresponding genes. In this TWAS, we identified novel candidate susceptibility genes for prostate cancer risk, providing new insights into prostate cancer genetics and biology. What's new? Although an estimated 58 percent of prostate cancers are linked to familial factors, most heritable risk variants for prostate cancer remain unidentified. In this transcriptome‐wide association study, data from the Genotype‐Tissue Expression Project was used to construct models for investigating associations between genetically determined gene expression and prostate cancer risk. In total, 573 candidate genes for prostate cancer risk were identified, including 451 newly linked to risk. Of candidate genes, 152 exhibited differential expression between tumor and adjacent normal tissue, while CpG sites in some genes showed differences in methylation. Additional evidence suggests that several genes identified influence prostate tumorigenesis. [ABSTRACT FROM AUTHOR]

Background: Limited real‐world data exist on treatment patterns and outcomes in patients with metastatic castration‐sensitive prostate cancer (mCSPC). Methods: A retrospective cohort study was conducted, using the Veterans Health Administration claims database (April 2013–March 2018). Among 369,734 prostate cancer patients, we selected all men who developed metastases within 90 days before or after medical/surgical castration and who received androgen deprivation therapy (ADT). Patients were categorized into four cohorts: ADT‐only (± <90‐day nonsteroidal anti‐androgen [NSAA] use), ADT + NSAA, ADT + docetaxel, and ADT + abiraterone. Main outcomes were treatment patterns, time‐to‐progression to metastatic castration‐resistant disease, and overall survival. Multivariable analysis and sensitivity analysis were conducted. Results: Of 1395 patients, 874 (63%) received ADT‐only, 338 (24%) received ADT + NSAA, 108 (8%) received ADT + docetaxel, and 75 (5%) received ADT + abiraterone. Proportions on ADT‐only and ADT + NSAA declined (from 66% to 60% and from 31% to 17%, respectively) over the study period, while proportions prescribed ADT + docetaxel or abiraterone increased from 3% to 9% and from 1% to 15%, respectively. Patients treated with ADT + NSAA had similar risks of castration‐resistant disease (hazard ratio [HR] 1.05; 95% confidence interval [CI]: 0.87, 1.26) and overall mortality (HR 1.22; 95% CI: 0.97, 1.54) as ADT‐only. Conclusions: Most patients with mCSPC initiating ADT received ADT‐only or ADT + NSAA, despite the emergence of docetaxel and novel hormonal therapies. Even in the most recent period (2017 to early 2018), only 24% of men received intensified therapy with agents known to prolong survival versus ADT‐only. These data in real‐world clinical practice suggest substantial room for improved outcomes in patients with mCSPC. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to describe bladder cancer outcomes as a function of race among patients with high‐risk non–muscle‐invasive bladder cancer (NMIBC) in an equal‐access setting. Methods: A total of 412 patients with high‐risk NMIBC who received bacille Calmette‐Guérin (BCG) from January 1, 2010, to December 31, 2015, were assessed. The authors used the Kaplan‐Meier method to estimate event‐free survival and Cox regression to determine the association between race and recurrence, progression, disease‐specific, and overall survival outcomes. Results: A total of 372 patients who had complete data were included in the analysis; 48 (13%) and 324 (87%) were Black and White, respectively. There was no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. White patients had a higher socioeconomic status with a greater percentage of patients living above the poverty level in comparison with Black patients (median, 85% vs 77%; P <.001). A total of 360 patients (97%) received adequate induction BCG, and 145 patients (39%) received adequate maintenance BCG therapy. There was no significant difference in rates of adequate induction or maintenance BCG therapy according to race. There was no significant difference in recurrence (hazard ratio [HR], 1.53; 95% confidence interval [CI], 0.64‐3.63), progression (HR, 0.77; 95% CI, 0.33‐1.82), bladder cancer–specific survival (HR, 1.01; 95% CI, 0.30‐3.46), or overall survival (HR, 0.97; 95% CI, 0.56‐1.66) according to Black race versus White race. Conclusions: In this small study from an equal‐access setting, there was no difference in the receipt of BCG or any differences in bladder cancer outcomes according to race. In this population‐based study within the largest equal‐access setting in the United States, among patients with high‐risk non–muscle‐invasive bladder cancer, there is no difference in age, sex, smoking status, or Charlson Comorbidity Index by race. There is no significant difference in rates of adequate induction or maintenance bacille Calmette‐Guérin therapy or any other outcomes measured according to race. [ABSTRACT FROM AUTHOR]

Objective: Older patients diagnosed with cancer are at increased risk of physical and emotional distress; however, prescription utilization patterns largely remain to be elucidated. Our objective was to comprehensively assess prescription patterns and predictors in older patients with bladder cancer. Methods: A total of 10,516 older patients diagnosed with clinical stage T1–T4a, N0, M0 bladder urothelial carcinoma from 1 January 2008 to 31 December 2012 from the Surveillance, Epidemiology, and End Results (SEER)‐Medicare were analyzed. We used multivariable analysis to determine predictors associated with psychotropic prescription rates (one or more). Medication possession ratio (MPR) was used as an index to measure adherence in intervals of 3 months, 6 months, 1 year, and 2 years. Evaluation of psychotropic prescribing patterns and adherence across different drugs and demographic factors was done. Results: Of the 10,516 older patients, 5621 (53%) were prescribed psychotropic drugs following cancer diagnosis. Overall, 3972 (38%) patients had previous psychotropic prescriptions prior to cancer diagnosis, and these patients were much more likely to receive a post‐cancer diagnosis prescription. Prescription rates for psychotropic medications were higher among patients with higher stage BC (p < 0.001). Gamma aminobutyric acid modulators/stimulators and serotonin reuptake inhibitors/stimulators were the highest prescribed psychotropic drugs in 21% of all patients. Adherence for all drugs was 32% at 3 months and continued to decrease over time. Conclusion: Over half of the patients received psychotropic prescriptions within 2 years of their cancer diagnosis. Given the chronicity of psychiatric disorders with observed significantly low adherence to medications that warrants an emphasis on prolonged patient monitoring and further investigation. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effect of a preexisting posttraumatic stress disorder (PTSD) diagnosis on suicide and non-suicide mortalities among men with newly diagnosed prostate cancer, and examine potential mediating factors for the relationship between PTSD and suicide.Methods: We used patient-level data from Veterans Health Administration electronic medical records to identify men (age ≥40 years) diagnosed with prostate cancer between 2004 and 2014. We used Fine and Gray regression model to estimate the risk for competing mortality outcomes (suicide, non-suicide, and alive). We used structural equation models to evaluate the mediating factors.Results: Our cohort comprised 214,649 men with prostate cancer, of whom 12,208 (5.7%) had a preexisting PTSD diagnosis. Patients with PTSD compared to those without utilized more healthcare services and had lower risk cancer at diagnosis. Additionally, they experienced more suicide deaths (N = 26, 0.21% vs. N = 269, 0.13%) and fewer non-suicide deaths (N = 1399, 11.5% vs. N = 45,625, 22.5%). On multivariable analysis, PTSD was an independent suicide risk factor (HR = 2.35; 95% CI: 1.16, 4.78). Depression, substance use disorder, and any definitive prostate cancer treatment were partial mediators. However, PTSD was associated with lower non-suicide mortality risk (HR = 0.86; 95% CI: 0.77, 0.96).Conclusion: Patients with PTSD experienced greater suicide risk even after adjusting for important mediators. They may have experienced lower non-suicide mortality risk due to favorable physical health resulting from greater healthcare service use and early diagnosis of lower risk cancer. Our findings highlight the importance of considering psychiatric illnesses when treating patients with prostate cancer and the need for interventions to ameliorate suicide risk. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association between obesity and positive surgical margins in patients undergoing retropubic radical prostatectomy versus robotic‐assisted laparoscopic prostatectomy. Methods: We retrospectively reviewed the data of 3141 men undergoing retropubic radical prostatectomy and 1625 undergoing robotic‐assisted laparoscopic prostatectomy between 1988 and 2017 at eight Veterans Health Administration hospitals. The positive surgical margin location (peripheral, apical, bladder neck, overall) was determined from pathology reports. We adjusted for age, race, prostate‐specific antigen, surgery year, prostate weight, pathological grade group, extracapsular extension, seminal vesicle invasion, hospital surgical volume and surgical method (in analyses not stratified by surgical method). Interactions between body mass index and surgical approach were tested. Results: Among all patients, higher body mass index was associated with increased odds of overall, peripheral and apical positive surgical margins (OR 1.02–1.03, P ≤ 0.02). Although not statistically significant, there was a trend between higher body mass index and increased odds of bladder neck positive surgical margins (OR 1.03, P = 0.09). Interactions between body mass index and surgical method were significant for peripheral positive surgical margins only (P = 0.024). Specifically, there was an association between body mass index and peripheral positive surgical margins among men undergoing retropubic radical prostatectomy (OR 1.04, P < 0.001), but not robotic‐assisted laparoscopic prostatectomy (OR 1.00, P = 0.98). Limitations include lacking individual surgeon data and lacking central pathology review. Conclusions: In this multicenter cohort, higher body mass index was associated with increased odds of positive surgical margins at all locations except the bladder neck. Furthermore, there was a significant association between obesity and peripheral positive surgical margins in men undergoing retropubic radical prostatectomy, but not robotic‐assisted laparoscopic prostatectomy. Long‐term clinical significance requires further study. [ABSTRACT FROM AUTHOR]

Background: The authors previously found that obesity was linked with prostate cancer (PC)-specific mortality (PCSM) among men who underwent radical prostatectomy (RP). Herein, in a larger RP cohort, the authors investigated whether the association between obesity and long-term PC outcomes, including PCSM, differed by race.Methods: Data from 5929 patients who underwent RP and were in the Shared Equal Access Regional Cancer Hospital (SEARCH) database were analyzed. Prior to RP, body mass index (BMI) was measured and recorded in the medical records. BMI was categorized as normal weight (<25 kg/m2 ), overweight (25-29.9 kg/m2 ), and obese (≥30 kg/m2 ). The authors assessed the association between BMI and biochemical disease recurrence (BCR), castration-resistant prostate cancer (CRPC), metastasis, and PCSM, accounting for confounders.Results: Of the 5929 patients, 1983 (33%) were black, 1321 (22%) were of normal weight, 2605 (44%) were overweight, and 2003 (34%) were obese. Compared with white men, black men were younger; had higher prostate-specific antigen levels; and were more likely to have a BMI ≥30 kg/m2 , seminal vesicle invasion, and positive surgical margins (all P ≤ .032). During a median follow-up of 7.4 years, a total of 1891 patients (32%) developed BCR, 181 patients (3%) developed CRPC, 259 patients (4%) had metastasis, and 135 patients (2%) had died of PC. On multivariable analysis, obesity was found to be associated with an increased risk of PCSM (hazard ratio, 1.78; 95% confidence interval, 1.04-3.04 [P = .035]). No interaction was found between BMI and race in predicting PCSM (P ≥ .88), BCR (P ≥ .81), CRPC (P ≥ .88), or metastasis (P ≥ .60). Neither overweight nor obesity was associated with risk of BCR, CRPC, or metastasis (all P ≥ .18).Conclusions: Obese men undergoing RP at several Veterans Affairs hospitals were found to be at an increased risk of PCSM, regardless of race. [ABSTRACT FROM AUTHOR]

Background: The impact of race on prostate cancer skeletal-related events (SREs) remains understudied. In the current study, the authors tested the impact of race on time to SREs and overall survival in men with newly diagnosed, bone metastatic castration-resistant prostate cancer (mCRPC).Methods: The authors performed a retrospective study of patients from 8 Veterans Affairs hospitals who were newly diagnosed with bone mCRPC in the year 2000 or later. SREs comprised pathologic fracture, spinal cord compression, radiotherapy to the bone, or surgery to the bone. Time from diagnosis of bone mCRPC to SREs and overall mortality was estimated using the Kaplan-Meier method. Cox models tested the association between race and SREs and overall mortality.Results: Of 837 patients with bone mCRPC, 232 patients (28%) were black and 605 (72%) were nonblack. At the time of diagnosis of bone mCRPC, black men were found to be more likely to have more bone metastases compared with nonblack men (29% vs 19% with ≥10 bone metastases; P = .021) and to have higher prostate-specific antigen (41.7 ng/mL vs 29.2 ng/mL; P = .005) and a longer time from the diagnosis of CRPC to metastasis (17.9 months vs 14.3 months; P < .01). On multivariable analysis, there were no differences noted with regard to SRE risk (hazard ratio [HR], 0.80; 95% CI, 0.59-1.07) or overall mortality (HR, 0.87; 95% CI, 0.73-1.04) between black and nonblack people, although the HRs were <1, which suggested the possibility of better outcomes.Conclusions: No significant association between black race and risk of SREs and overall mortality was observed in the current study. These data have suggested that efforts to understand the basis for the excess risk of aggressive prostate cancer in black men should focus on cancer development and progression in individuals with early-stage disease. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) is the main treatment strategy for men with metastatic prostate cancer (PC). However, ADT is associated with various metabolic disturbances, including impaired glucose tolerance, insulin resistance and weight gain, increasing risk of diabetes and cardiovascular death. Much remains unknown about the metabolic pathways and disturbances altered by ADT and the mechanisms. We assessed the metabolomic effects of ADT in the serum of 20 men receiving ADT. Sera collected before (baseline), 3 and 6 months after initiation of ADT was used for the metabolomics and lipidomics analyses. The ADT‐associated metabolic changes were identified by univariable and multivariable statistical analysis, ANOVA, and Pearson correlation. We found multiple key changes. First, ADT treatments reduced the steroid synthesis as reflected by the lower androgen sulfate and other steroid hormones. Greater androgen reduction was correlated with higher serum glucose levels, supporting the diabetogenic role of ADT. Second, ADT consistently decreased the 3‐hydroxybutyric acid and ketogenesis. Third, many acyl‐carnitines were reduced, indicating the effects on the fatty acid metabolism. Fourth, ADT was associated with a corresponding reduction in 3‐formyl indole (a.k.a. indole‐3‐carboxaldehyde), a microbiota‐derived metabolite from the dietary tryptophan. Indole‐3‐carboxaldehyde is an agonist for the aryl hydrocarbon receptor and regulates the mucosal reactivity and inflammation. Together, these ADT‐associated metabolomic analyses identified reduction in steroid synthesis and ketogenesis as prominent features, suggesting therapeutic potential of restricted ketogenic diets, though this requires formal testing. ADT may also impact the microbial production of indoles related to the immune pathways. Future research is needed to determine the functional impact and underlying mechanisms to prevent ADT‐linked comorbidities and diabetes risk. [ABSTRACT FROM AUTHOR]

Objective: To test the association between statin use and prostate volume (PV) change over time using data from the REduction by DUtasteride of prostate Cancer Events (REDUCE) trial, a 4‐year randomised controlled trial testing dutasteride for prostate cancer chemoprevention. Subjects/Patients and Methods: We identified men with a baseline negative prostate biopsy from REDUCE who did not undergo prostate surgery or develop prostate cancer over the trial period. Men reported statin use at baseline. PV was determined from transrectal ultrasonography performed to guide prostate biopsy at baseline, and 2‐ and 4‐years after randomisation. Multivariable generalised estimating equations tested differences in PV change over time by statin use, overall and stratified by treatment arm. We tested for interactions between statins and time in association with PV using the Wald test. Results: Of 4106 men, 17% used statins at baseline. Baseline PV did not differ by statin use. Relative to non‐users, statin users had decreasing PVs over the trial period (P = 0.027). Similar patterns were seen in the dutasteride and placebo arms, although neither reached statistical significance. The mean estimated PV was modestly but significantly lower in statin users relative to non‐users in the dutasteride arm at 2‐years (4.5%, P = 0.032) and 4‐years (4.0%, P = 0.033), with similar (3–3.3%) but non‐significant effects in the placebo arm. Conclusion: If confirmed, our present findings support a role for statins in modestly attenuating PV growth, with a magnitude of effect in line with previously reported prostate‐specific antigen‐lowering effects of statins (~4%). Future studies are needed to assess whether this putative role for statins in PV growth could impact lower urinary tract symptom development or progression. [ABSTRACT FROM AUTHOR]

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

Background: The current study was performed to evaluate the influence of race on the association between biopsy grade group (GrGp) and the risk of detectable prostate‐specific antigen (PSA) and adverse histopathological outcomes after radical prostatectomy (RP). Methods: Data regarding 4073 men (1344 African American men; 33%) who were treated with RP were categorized based on the 5‐tiered GrGp system. Logistic regression was used to test the association between biopsy GrGp and PSA nadir (<0.1 ng/mL) after RP as well as adverse pathological features among all patients and stratified by race. Results: Those patients with a higher biopsy GrGp were found to have lower odds of achieving a PSA nadir <0.1 ng/mL after RP on unadjusted and multivariable analysis (both P < .001). On unadjusted and multivariable analysis, higher GrGp was associated with increased odds of each of the adverse pathological features, namely, GrGp ≥3, extraprostatic extension, seminal vesicle invasion, positive surgical resection margin, and positive lymph nodes (all P < .001). Race had no significant interaction with biopsy GrGp in the prediction of PSA nadir after RP (P = .91) or any adverse pathological features (all P > .06) except positive lymph nodes. When the models were stratified by race, the associations between preoperative biopsy GrGp and having a PSA nadir <0.1 ng/mL, high‐grade final pathology, or other adverse histopathologic features were similar in both races except as noted for positive lymph nodes. Conclusions: Higher preoperative biopsy GrGp is associated with increased odds of adverse histopathological findings as well as lower odds of a PSA nadir <0.1 ng/mL after RP. These associations are largely independent of race, suggesting that GrGp is an accurate tool for risk stratification in both black and white men. Higher preoperative biopsy grade group is associated with increased odds of adverse pathological findings as well as lower odds of a prostate‐specific antigen nadir <0.1 ng/mL after radical prostatectomy. These associations are largely independent of race, indicating that grade group is an accurate tool for risk stratification in both black and white men. [ABSTRACT FROM AUTHOR]

Aims: The complexity of Interstitial Cystitis/bladder Pain Syndrome (IC/BPS) has led to a great deal of uncertainty around the diagnosis and prevalence of the condition. Under the hypothesis that IC/BPS is frequently misdiagnosed, we sought to assess the accuracy of the ICD‐9/ICD‐10 code for IC/BPS using a national data set. Methods: Using the Veterans Affairs Informatics and Computing Infrastructure, we identified a random sample of 100 patients with an ICD‐9/ICD‐10 diagnosis of IC/BPS (595.1/N30.10) by querying all living patients in the Veterans Affairs (VA) system. We purposely sampled men and women equally to better understand gender‐specific practice patterns. Patients were considered a correct IC/BPS diagnosis if they had two visits complaining of bladder‐centric pain in the absence of positive urine culture at least 6 weeks apart. Patients were considered not to have IC/BPS if they had a history of pelvic radiation, systemic chemotherapy, metastatic cancer, or bladder cancer. Results: Of the 100 patients, 48 were female and 52 were male. Five had prior radiation, one had active cancer, and 10 had bladder cancer (all male), and an additional fifteen had insufficient records. Of the remaining 69 patients, 43% did not have IC/BPS. Of these patients who did not have IC/BPS, 43% complained only of overactive bladder (OAB) symptoms, which was more common in women (63%) than men (21%), P = .003. Conclusions: In our small sample from a nationwide VA system, results indicate that IC/BPS has a high misdiagnosis rate. These findings shed light on the gender‐specific diagnostic complexity of IC/BPS. [ABSTRACT FROM AUTHOR]

Background: Although diabetes is inversely related to prostate cancer (PC) risk, to the authors' knowledge the impact of glycemic control on PC progression is unknown. In the current study, the authors tested the association between hemoglobin A1c (HbA1c) and long-term PC outcomes among diabetic men undergoing radical prostatectomy (RP).Methods: The authors retrospectively reviewed data regarding men undergoing RP from 2000 to 2017 at 8 Veterans Affairs hospitals. Diabetic patients were identified using International Classification of Diseases, Ninth Revision (ICD-9) codes (250.x) or by an HbA1c value >6.5% at any time before RP. Cox models tested the association between HbA1c and biochemical disease recurrence (BCR), castration-resistant PC (CRPC), metastases, PC-specific mortality, and all-cause mortality. The model for BCR was adjusted for multiple variables. Due to limited events, models for long-term outcomes were adjusted for biopsy grade and prostate-specific antigen only.Results: A total of 1409 men comprised the study population. Of these, 699 patients (50%) had an HbA1c value <6.5%, 631 (45%) had an HbA1c value of 6.5% to 7.9%, and 79 (6%) had an HbA1c value ≥8.0%. Men with an HbA1c value ≥8.0% were younger (P < .001) and more likely to be black (P = .013). The median follow-up after RP was 6.8 years (interquartile range, 3.7-10.6 years). On multivariable analysis, HbA1c was not found to be associated with BCR. However, a higher HbA1c value was associated with metastasis (hazard ratio [HR], 1.21; 95% CI, 1.02-1.44 [P = .031]) and CRPC (HR, 1.27; 95% CI, 1.03-1.56 [P = .023]). Although not statistically significant, there were trends between higher HbA1c and risk of PC-specific mortality (HR, 1.24; 95% CI, 0.99-1.56 [P = .067]) and all-cause mortality (HR, 1.09; 95% CI, 0.99-1.19 [P = .058]).Conclusions: Among diabetic men undergoing RP, a higher HbA1c value was associated with metastases and CRPC. If validated in larger studies with longer follow-up, future research should test whether better glycemic control improves long-term PC outcomes. [ABSTRACT FROM AUTHOR]

Objectives: To examine the association between body mass index (BMI) and aggressive biochemical recurrence (BCR) using the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Material and Methods: We identified 4123 men with complete data treated by radical prostatectomy between 1988 and 2015. We tested the association between BMI and BCR using Cox models, and among men with BCR, prostate‐specific antigen doubling time (PSADT) was compared across BMI categories using linear regression. Models were adjusted for age, race, prostate‐specific antigen, biopsy Gleason score, clinical stage, year and surgical centre. Results: Overall, 922 men (22%) were of normal weight (BMI <25 kg/m2), 1863 (45%) were overweight (BMI 25–29.9 kg/m2), 968 (24%) 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 BCR (P = 0.008). Among men with BCR, men in the four BMI categories had similar multivariable‐adjusted PSADT values (increasing BMI categories: 20.9 vs 21.3 vs 21.0 vs 14.9 months; P = 0.48). Conclusion: While we confirmed that higher BMI was associated with BCR, we found no link between BMI and PSADT at the time of recurrence. Our data suggest obese men do not have more aggressive recurrences. Future studies are needed to test whether obesity predicts response to salvage therapies. [ABSTRACT FROM AUTHOR]

Background: In this study among men who underwent radical prostatectomy (RP), African American men (AAM) were 28% more likely to develop recurrent disease compared with Caucasian men (CM). However, among those who had nonmetastatic, castration-resistant prostate cancer (CRPC), race did not predict metastases or overall survival. Whether race predicts metastases among men who receive androgen-deprivation therapy (ADT) after a biochemical recurrence (BCR) (ie, before CRPC but after BCR) is untested.Methods: The authors identified 595 AAM and CM who received ADT for a BCR that developed after RP between 1988 and 2015 in the Shared Equal-Access Regional Cancer Hospital (SEARCH) database. Univariable and multivariable Cox models were used to test the association between race and the time from ADT to metastases. Secondary outcomes included the time to CRPC, all-cause mortality, and prostate cancer-specific mortality.Results: During a median follow-up of 66 months after ADT, 62 of 354 CM (18%) and 38 of 241 AAM (16%) developed metastases. AAM were younger at the time they received ADT (63 vs 67 years; P < .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).Conclusions: Among veterans who received ADT post-BCR after RP, race was not a predictor of metastases or other adverse outcomes. The current findings suggest that research efforts to understand racial differences in prostate cancer biology should focus on early stages of the disease (ie, closer to the time of diagnosis). [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the association between acute and chronic inflammation with the presence of perineural invasion (PNI) in prostate biopsies positive for prostate cancer (PCa). Material and Methods: We conducted a retrospective analysis of 1 399 prostate biopsies positive for PCa in the Reduction by Dutasteride of PCa Events (REDUCE) study. PCa, acute and chronic prostate inflammation and PNI were assessed by central pathology review. The association between acute and chronic inflammation with PNI was evaluated using chi‐squared and Kruskal–Wallis tests, and logistic regression adjusting for clinicopathological and biochemical variables. Results: The presence of PNI was identified in 133 biopsies (9.5%). In all, 267 biopsies (19.1%) had acute inflammation, 1 038 (74.2%) had chronic inflammation, and 255 (18.2%) had both. The presence of both acute and chronic inflammation had a mutual association (P < 0.001). Chronic inflammation was associated with a lower Gleason score (P = 0.009) and lower tumour volume (P < 0.001), while acute inflammation was associated with lower Gleason score (P = 0.04), lower tumour volume (P = 0.004) and higher prostate‐specific antigen levels (P = 0.05). In both univariable and multivariable analyses, chronic prostate inflammation was significantly associated with less PNI (univariable odds ratio [OR] 0.54, 95% confidence interval [CI] 0.37–0.79, P = 0.001; multivariable OR 0.65, 95% CI 0.43–0.99, P = 0.045). Acute prostate inflammation was associated with less PNI only in univariable analysis (univariable OR 0.51, 95% CI 0.29–0.89, P = 0.018; multivariable OR 0.63, 95% CI 0.35–1.13, P = 0.12). Conclusion: Acute and chronic prostate inflammation were both associated with a lower prevalence of PNI in prostate biopsies positive for PCa. If confirmed, this suggests that inflammation and immunomodulation can serve as areas of potential therapeutic design to mitigate PNI in patients with PCa. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the impact of previous local treatment on survival in men with newly diagnosed metastatic castration‐resistant prostate cancer. Methods: We carried out a retrospective study of patients newly diagnosed with metastatic castration‐resistant prostate cancer in the year 2000 or later from eight Veterans Affairs Medical Centers. Patients were categorized based on prior local therapy (none, prostatectomy ± radiation or radiation alone). Overall and cancer‐specific survival was estimated by the Kaplan–Meier method. Cox proportional hazards regression models were used to test the association between prior local treatment and survival. Results: Of 729 patients, 284 (39%) underwent no local treatment, 176 (24%) underwent radical prostatectomy ± radiation and 269 (37%) underwent radiation alone. On multivariable analysis, men with prior prostatectomy had improved overall (hazard ratio 0.71, P = 0.005) and cancer‐specific survival (hazard ratio 0.55, P < 0.001) compared with men with no prior local therapy. This improvement in overall (hazard ratio 0.89, P = 0.219) and cancer‐specific survival (hazard ratio 0.87, P = 0.170) was not seen in men with prior radiation alone. After further adjusting for comorbidity with the Charlson Comorbidity Index, patients with prior prostatectomy still had improved overall survival (hazard ratio 0.70, P = 0.003), whereas this was not seen in patients who received prior radiation alone (hazard ratio 0.88, P = 0.185). Conclusions: Independent of patient‐ and disease‐related factors, men with metastatic castration‐resistant prostate cancer who had undergone prior radical prostatectomy have improved overall and cancer‐specific survival compared with those with no prior local therapy. [ABSTRACT FROM AUTHOR]

Objective: To evaluate biochemical recurrence (BCR) patterns amongst men undergoing radical prostatectomy (RP) with specimens having negative (NSM), positive (PSM), and close surgical margins (CSM) from the Shared Equal Access Regional Cancer Hospital (SEARCH) cohort, as PSM after RP are a significant predictor of biochemical failure and possible disease progression, with CSM representing a diagnostic challenge for surgeons. Patients and Methods: Men undergoing RP between 1988 and 2015 with known final pathological margin status were evaluated. The cohort was divided into three groups based on margin status; NSM, PSM, and CSM. CSM were defined by distance of tumour ≤1 mm from the surgical margin. BCR was defined as a prostate‐specific antigen (PSA) level of >0.2 ng/mL, two values at 0.2 ng/mL, or secondary treatment for an elevated PSA level. Predictors of BCR, metastases, and mortality were analysed using Cox proportional hazard models. Results: Of 5515 men in the SEARCH database, 4337 (79%) men met criteria for inclusion in the analysis. Of these, 2063 (48%) had NSM, 1902 (44%) had PSM, and 372 (8%) had CSM. On multivariable analysis, relative to NSM, men with CSM had a higher risk of BCR (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.25–1.82; P < 0.001) but a decreased risk of BCR when compared to those men with PSM (HR 2.09, 95% CI 1.86–2.36; P < 0.001). Metastases, prostate cancer‐specific mortality and all‐cause mortality did not differ based on margin status alone. Conclusions: Management of men with CSM is a diagnostic challenge, with a disease course that is not entirely benign. The evaluation of other known risk factors probably provides greater prognostic value for these men and may ultimately better select those who may benefit from adjuvant therapy. [ABSTRACT FROM AUTHOR]

Background: Treatments for muscle-invasive bladder cancer are multimodal, complex, and often carry significant risks of physical and psychological morbidity. The objectives of this study were to define the incidence and types of psychiatric illnesses diagnosed after treatment and to determine their impact on survival outcomes.Methods: In total, 3709 patients who were diagnosed with clinical stage T2 through T4a bladder cancer from January 1, 2002, to December 31, 2011, from the Surveillance, Epidemiology, and End Results-Medicare were analyzed. Multivariable analysis and Cox proportional-hazards models were used to determine the predictors associated with psychiatric diagnosis and impact on survival outcomes.Results: Of 3709 patients, 1870 (50.4%) were diagnosed with posttreatment psychiatric disorders. Patients who underwent radical cystectomy were identified as being at significantly greater risk of having a posttreatment psychiatric illness compared with those who received radiotherapy and/or chemotherapy (hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In adjusted analyses, diagnosis of a psychiatric disorder resulted in significantly worse overall survival (HR, 2.80; 95% CI, 2.47-3.17; P < .001) and cancer-specific survival (HR, 2.39; 95% CI, 2.05-2.78; P < .001).Conclusions: One-half of patients with muscle-invasive bladder cancer who underwent treatment were diagnosed with a psychiatric disorder, which resulted in worse survival outcomes compared with patients who did not have a posttreatment psychiatric diagnosis. This information can be used to inform interventions to educate patients with muscle-invasive bladder cancer regarding the impact of different treatments on mental health. Cancer 2018. © 2018 American Cancer Society. [ABSTRACT FROM AUTHOR]

Objective: To assess whether obesity is associated with progression to metastasis, prostate cancer‐specific mortality (PCSM), and all‐cause mortality (ACM), in patients with non‐metastatic castration‐resistant prostate cancer (non‐mCRPC). At the population level, obesity is associated with prostate cancer mortality; however, some studies have found that higher body mass index (BMI) is associated with better long‐term prostate cancer outcomes amongst men with mCRPC. Patients and Methods: We identified 1 192 patients with non‐mCRPC from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. BMI was calculated from height and weight abstracted from the medical records at the time closest to but prior to CRPC diagnosis and categorised as underweight (<21 kg/m2), normal weight (21–24.9 kg/m2), overweight (25–29.9 kg/m2), and obese (≥30 kg/m2). Competing risks regression and Cox models were used to test associations between obesity and progression to metastasis, PCSM, and ACM, accounting for confounders. Results: Overall, 51 (4%) men were underweight, 239 (25%) were normal weight, 464 (39%) were overweight, and 438 (37%) were obese. In adjusted analysis, higher BMI was significantly associated with reduced ACM (hazard ratio [HR] 0.98, P = 0.012) but not PCSM (HR 1.00, P = 0.737) or metastases (HR 0.99, P = 0.225). Likewise, when BMI was treated as a categorical variable in adjusted models, obesity was not associated with PCSM (HR 1.11, P = 0.436) or metastases (HR 1.06, P = 0.647), but was associated with decreased ACM (HR 0.79, P = 0.016) compared to normal weight. No data were available on treatments received after CRPC diagnosis. Conclusions: Amongst patients with non‐mCRPC obesity was associated with better overall survival. Although this result mirrors evidence from men with mCRPC, obesity was not associated with prostate cancer outcomes. Larger studies are needed to confirm these findings. [ABSTRACT FROM AUTHOR]

Objectives To determine the prognostic utility of the cell cycle progression ( CCP) score in men with National Comprehensive Cancer Network ( NCCN)-defined low-risk prostate cancer ( PCa) undergoing radical prostatectomy ( RP). Patients and Methods Men who underwent RP for Gleason score ≤6 PCa at three institutions (Martini Clinic [ MC], Durham Veterans Affairs Medical Center [ DVA] and Intermountain Healthcare [ IH]) were identified. The CCP score was obtained from diagnostic ( DVA, IH) or simulated biopsies ( MC). The primary outcome was biochemical recurrence ( BCR; prostate-specific antigen ≥0.2 ng/ mL) after RP. The prognostic utility of the CCP score was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards models in the subset of men meeting NCCN low-risk criteria and in the overall cohort. Results Among the 236 men identified, 80% (188/236) met the NCCN low-risk criteria. Five-year BCR-free survival for the low (<0), intermediate (0-1) and high (>1) CCP score groups was 89.2%, 80.4%, 64.7%, respectively, in the low-risk cohort ( P = 0.03), and 85.9%, 79.1%, 63.1%, respectively, in the overall cohort ( P = 0.041). In multivariable models adjusting for clinical and pathological variables with the Cancer of the Prostate Risk Assessment ( CAPRA) score, the CCP score was an independent predictor of BCR in the low-risk (hazard ratio [ HR] 1.77 per unit score, 95% confidence interval [ CI] 1.21, 2.58; P = 0.003) and overall cohorts ( HR 1.41 per unit score, 95% CI 1.02, 1.96; P = 0.039). Conclusion In a cohort of men with NCCN-defined low-risk PCa, the CCP score improved clinical risk stratification of men who were at increased risk of BCR, which suggests the CCP score could improve the assessment of candidacy for active surveillance and guide optimum treatment selection in these patients with otherwise similar clinical characteristics. [ABSTRACT FROM AUTHOR]

Objectives To examine whether prostate-specific antigen doubling time ( PSADT) correlates with metastases, all-cause mortality ( ACM), and prostate cancer-specific mortality ( PCSM) and to identify PSADT thresholds that can be used clinically for risk stratification in men with M0 castration-resistant prostate cancer ( CRPC). Materials and Methods We collected data on 441 men with M0 CRPC in 2000-2015 at five Veterans Affairs hospitals. Cox models were used to test the association between log-transformed PSADT and the development of metastasis, ACM and PCSM. To identify thresholds, we categorized PSADT into 3-month groups and then combined groups with similar hazard ratios ( HRs). Results The median (interquartile range) follow-up was 28.3 (14.7-49.1) months. As a continuous variable, PSADT was associated with metastases, ACM and PCSM ( HR 1.40-1.68, all P < 0.001). We identified the following PSADT thresholds: <3 months; 3-8.9 months; 9-14. months; and ≥15 months. As a categorical variable, PSADT was associated with metastases, ACM and PCSM (all P < 0.001). Specifically, PSADT <3 months was associated with an approximately ninefold increased risk of metastases ( HR 8.63, 95% CI 5.07-14.7) and PCSM ( HR 9.29, 95% CI 5.38-16.0), and a 4.7-fold increased risk of ACM ( HR 4.71, 95% CI 2.98-7.43) on multivariable analysis compared with PSADT ≥15 months. The median times to metastasis for patients with PSADT <3, 3-8.9, 9-14.9 and ≥15 months were 9, 19, 40 and 50 months, respectively. Conclusion Prostate-specific antigen doubling time was a strong predictor of metastases, ACM and PCSM in patients with M0 CRPC. As with patients at earlier disease stages, <3, 3-8.9, 9-14.9 and ≥15 months are reasonable PSADT thresholds for risk stratification in men with M0 CRPC. These thresholds can be used for selecting high-risk men for clinical trials. [ABSTRACT FROM AUTHOR]

Background: Black race is associated with prostate cancer (PC) diagnosis and poor outcome. Previously, the authors reported that black men undergoing radical prostatectomy (RP) in equal-access hospitals had an increased risk of biochemical disease recurrence (BCR), but recurrences were equally aggressive as those occurring in white men. The authors examined the association between race and long-term outcomes after RP.Methods: Data regarding 1665 black men (37%) and 2791 white men (63%) undergoing RP were analyzed. Using Cox models, the authors tested the association between race and BCR, BCR with a prostate-specific antigen (PSA) doubling time <9 months (aggressive disease recurrence), metastases, PC-specific death, and overall death.Results: At a median follow-up of 102 months, 1566 men (35%) developed BCR, 217 men (5%) experienced aggressive disease recurrence, 193 men (4%) developed metastases, and 1207 men (27%) had died, 107 of whom (2%) died of PC. White men were older and had a lower preoperative PSA level, a lower biopsy and pathological grade group, and more capsular penetration but less seminal vesicle invasion and positive surgical margins versus black men (all P<.05). Black men were found to have a more recent surgery year (P<.001). On univariable analysis, black race was associated with increased BCR (P = .003) and reduced overall death (P = .017). On multivariable analysis, black race was not found to be associated with BCR (hazard ratio [HR], 1.07; P = .26), aggressive recurrence (HR, 1.14; P = .42), metastasis (HR, 1.24; P = .21), PC-specific death (HR, 1.03; P = .91), or overall death (HR, 1.03; P = .67).Conclusions: Among men undergoing RP at equal-access centers, although black men were found to have an increased risk of BCR, they had similar risks of aggressive disease recurrence, metastasis, and PC-specific death compared with white men, and the risk of BCR was found to be similar after controlling for risk parameters. Longer follow-up is needed to confirm these findings. Cancer 2017;123:4199-4206. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

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

Objectives To better predict operative time using patient/surgical characteristics among men undergoing radical retropubic prostatectomy or robot-assisted laparoscopic prostatectomy in order to achieve more efficient operative scheduling and potentially decrease costs in the Veterans Health System. Methods We analyzed 2619 men treated with radical retropubic prostatectomy ( n = 2005) or robot-assisted laparoscopic prostatectomy ( n = 614) from 1993 to 2013 from six Veterans Affairs Hospitals in the Shared Equal Access Regional Cancer Hospital database. Age, body mass index, race, biopsy Gleason, prostate weight, undergoing a nerve-sparing procedure or lymph node dissection, and hospital surgical volume were analyzed in multivariable linear regression to identify predictors of operative time and to quantify the increase/decrease observed. Results In men undergoing radical retropubic prostatectomy, body mass index, black race, prostate weight and a lymph node dissection all predicted longer operative times (all P ≤ 0.004). In men undergoing robot-assisted laparoscopic prostatectomy, biopsy Gleason score and a lymph node dissection were associated with increased operative time ( P ≤ 0.048). In both surgical methods, a lymph node dissection added 25-40 min to the operation. Also, in both, each additional operation per year per center predicted a 0.80-0.89-min decrease in operative time ( P ≤ 0.001). Conclusions Overall, several factors seem to be associated with quantifiable changes in operative time. If confirmed in future studies, these findings can allow for a more precise estimate of operative time, which could decrease the overall cost to the patient and hospital by aiding in operating room time management. [ABSTRACT FROM AUTHOR]

Objectives To examine if there is a subset of men with grade group 2 prostate cancer who could be potential candidates for active surveillance. Methods We used the Shared Equal Access Regional Cancer Hospital database to identify 776 men undergoing radical prostatectomy from 2006 to 2015 with >8 biopsy cores obtained and complete information. We compared men who fulfilled low-risk disease criteria (clinical stage T1c/T2a; grade group 1; prostate-specific antigen ≤10 ng/mL) with the exception of grade group 2 versus men who met all three low-risk criteria. Logistic regression was used to test the association between grade group and radical prostatectomy pathological features. Biochemical recurrence was examined using Cox models. To examine whether there was a subset of men with low-volume grade group 2 with comparable outcomes to low-risk men, we repeated all analyses limiting the percentage of positive cores in the grade group 2 group to ≤33%, and positive cores to ≤4, ≤3 or ≤2. Results Grade group 2 low-risk men had increased risk of pathological grade group 3 or higher ( P < 0.001), extraprostatic extension ( P < 0.001), seminal vesicle invasion ( P < 0.001) and higher risk of biochemical recurrence (hazard ratio = 1.76, P = 0.006). Using increasingly strict definitions of low-volume disease, at ≤2 positive cores there was no difference in adverse pathology between groups (all P > 0.2), except higher pathological grade group ( P = 0.006). Biochemical recurrence was similar in men in grade group 1 and grade group 2 (hazard ratio = 1.24; P = 0.529). Conclusions Among men with prostate-specific antigen ≤10 ng/mL and clinical stage T1c/T2a, those in grade group 2 with ≤2 total positive cores have similar rates of adverse pathology and biochemical recurrence as men with grade group 1. [ABSTRACT FROM AUTHOR]

Background: Skeletal-related events (SREs) are common complications of bone metastatic castration-resistant prostate cancer (mCRPC). To the authors' knowledge, there are limited data regarding which factors predict SREs. The authors identified risk factors for SREs in men with bone mCRPC using characteristics commonly available in the medical record.Methods: Data from 454 patients with nonmetastatic CRPC were identified from 2 Veteran Affairs Medical Centers from 2000 through 2013. Among these men, 233 (51%) developed bone metastases during follow-up and represented the study cohort. First occurrence of an SRE was abstracted from the medical records. A stepwise multivariable Cox model was used to select the strongest predictors of time to SRE.Results: The median age of the patients at the time of diagnosis of bone mCRPC was 75 years (interquartile range, 68-81 years), and there were 153 nonblack patients (66%). During follow-up (median, 7.8 months [interquartile range, 2.9-18.3 months]), 88 patients (38%) had an SRE. On univariable analysis, more recent year of metastasis (hazard ratio [HR], 0.91), prostate-specific antigen doubling time of ≥9 months versus <9 months (HR, 0.50), and bone pain (HR, 3.34) were all found to be associated with SRE risk. On multivariable analysis, year of metastasis (HR, 0.93), biopsy Gleason score of 7 versus ≤6 (HR, 1.74), radiotherapy as the primary localized treatment versus none (HR, 2.33), and bone pain (HR, 3.64) were associated with SRE risk. The area under the curve for a multivariable model based upon these risk factors was 0.744.Conclusions: The authors identified several significant predictors of SREs among men with mCRPC. In particular, men with bone pain are at high risk of an SRE. If confirmed, future trials should focus on prolonging life and reducing SRE risk in patients with mCRPC with bone pain. Cancer 2017;123:1528-1535. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]