Modifying Effects of Genetic Variations on the Association Between Dietary Isothiocyanate Exposure and Non-muscle Invasive Bladder Cancer Prognosis in the Be-Well Study.

SCOPE: Dietary isothiocyanate (ITC) exposure from cruciferous vegetable (CV) intake may improve non-muscle invasive bladder cancer (NMIBC) prognosis. This study aims to investigate whether genetic variations in key ITC-metabolizing/functioning genes modify the associations between dietary ITC exposure and NMIBC prognosis outcomes. METHODS AND RESULTS: In the Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study), a prospective cohort of 1472 incident NMIBC patients, dietary ITC exposure is assessed by self-reported CV intake and measured in plasma ITC-albumin adducts. Using Cox proportional hazards regression models, stratified by single nucleotide polymorphisms (SNPs) in nine key ITC-metabolizing/functioning genes, it is calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression. The rs15561 in N-acetyltransferase 1 (NAT1) is alter the association between CV intake and progression risk. Multiple SNPs in nuclear factor E2-related factor 2 (NRF2) and nuclear factor kappa B (NFκB) are modify the associations between plasma ITC-albumin adduct level and progression risk (pint < 0.05). No significant association is observed with recurrence risk. Overall, >80% study participants are present with at least one protective genotype per gene, showing an average 65% reduction in progression risk with high dietary ITC exposure. CONCLUSION: Despite that genetic variations in ITC-metabolizing/functioning genes may modify the effect of dietary ITCs on NMIBC prognosis, dietary recommendation of CV consumption may help improve NMIBC survivorship.

Environmental and Occupational Exposures and Prognosis in Patients with Non-Muscle Invasive Bladder Cancer in the Be-Well Study.

Bladder cancer is primarily diagnosed as non-muscle invasive bladder cancer (NMIBC) with high recurrence and progression rates. Environmental and occupational exposures to carcinogens are well-known risk factors for developing bladder cancer, yet their effects on prognosis remain unknown. In the Be-Well Study, a population-based prospective cohort study of 1,472 patient with newly diagnosed NMIBC from 2015 to 2019, we examined history of environmental and occupational exposures in relation to tumor stage and grade at initial diagnosis by multivariable logistic regression, and subsequent recurrence and progression by Cox proportional hazards regression. Exposure to environmental and occupational carcinogens was significantly associated with increased risk of progression (HR = 1.79; 95% CI: 1.04, 3.09), specifically increased progression into muscle-invasive disease (HR = 2.28; 95% CI: 1.16, 4.50). Exposure to asbestos and arsenic were associated with increased odds of advanced stage at diagnosis (asbestos: OR = 1.43; 95% CI: 1.11, 1.84; arsenic, OR = 1.27; 95% CI: 1.01, 1.63), and formaldehyde exposure was associated with increased risk of recurrence (HR = 1.38; 95% CI: 1.12, 1.69). Our findings suggest that history of these exposures may benefit current risk stratification systems to tailor clinical care and improve prognosis in patients with NMIBC.

Associations of dietary isothiocyanate exposure from cruciferous vegetable consumption with recurrence and progression of non-muscle-invasive bladder cancer: findings from the Be-Well Study.

BACKGROUND: High recurrence and progression rates are major clinical challenges for non-muscle-invasive bladder cancer (NMIBC). Dietary isothiocyanates (ITCs), phytochemicals primarily from cruciferous vegetables (CV), show strong anticancer activities in preclinical BC models, yet their effect on NMIBC prognosis remains unknown. OBJECTIVES: This study aimed to investigate the associations of dietary ITC exposure at diagnosis with NMIBC recurrence and progression. METHODS: The study analyzed 1143 participants from the Be-Well study, a prospective cohort of newly diagnosed NMIBC cases in 2015-2019 with no prior history of BC. Dietary ITC exposure was indicated by self-reported CV intake, estimated ITC intake, urinary metabolites, and plasma ITC-albumin adducts. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrence and progression, and unconditional logistic regression models were used to calculate odds ratios (ORs) and 95% CIs for delayed and multiple recurrence. RESULTS: Over a mean follow-up of 25 mo, 347 (30%) developed recurrence and 77 (6.7%) had disease progression. Despite no significant associations with the overall risk of recurrence, urinary ITC metabolites (OR: 1.96; 95% CI: 1.01, 4.43) and dietary ITC intake (OR: 2.13; 95% CI: 1.03, 4.50) were associated with late recurrence after 12-mo postdiagnosis compared with before 12-mo postdiagnosis. Raw CV intake was associated with reduced odds of having ≥2 recurrences compared with having one (OR: 0.34; 95% CI: 0.16, 0.68). Higher plasma concentrations of ITC-albumin adducts were associated with a reduced risk of progression, including progression to muscle-invasive disease (for benzyl ITC, HR: 0.40; 95% CI: 0.17, 0.93; for phenethyl ITC, HR: 0.40; 95% CI: 0.19, 0.86). CONCLUSIONS: Our findings indicate the possible beneficial role of dietary ITCs in NMIBC prognosis. Given the compelling preclinical evidence, increasing dietary ITC exposure with CV intake could be a promising strategy to attenuate recurrence and progression risks in patients with NMIBC.

Natural History of Multiple Recurrences in Intermediate-Risk Non-Muscle Invasive Bladder Cancer: Lessons From a Prospective Cohort.

OBJECTIVE: To describe the risk of multiple recurrences in intermediate-risk non-muscle invasive bladder cancer (IR-NMIBC) and their impact on progression. Prognostic studies of IR-NMIBC have focused on initial recurrences, yet little is known about subsequent recurrences and their impact on progression. MATERIALS AND METHODS: IR-NMIBC patients from the Be-Well Study, a prospective cohort study of NMIBC patients diagnosed from 2015 to 2019 at Kaiser Permanente Northern California, were identified. The frequency of first, second, and third intravesical recurrences of urothelial carcinoma were characterized using conditional Kaplan-Meier analyses and random-effects shared-frailty models. The association of multiple recurrences with progression was examined. RESULTS: In 291 patients with IR-NMIBC (median follow-up 38 months), the 5-year risk of initial recurrence was 54.4%. After initial recurrence (n = 137), 60.1% of patients had a second recurrence by 2 years. After second recurrence (n = 70), 51.5% of patients had a third recurrence by 3 years. In multivariable analysis, female sex (Hazard Ratio 1.51, P< .01), increasing tumor size (HR 1.14, P< .01) and number of prior recurrences (HR 1.24, P< .01) were associated with multiple recurrences; whereas maintenance BCG (HR 0.66, P = .03) was associated with reduced recurrences. The 5-year risk of progression varied significantly (P< .01) by number of recurrences: 9.5%, 21.9%, and 37.9% for patients with 1, 2, and 3+ recurrences, respectively. CONCLUSIONS: Multiple recurrences are common in IR-NMIBC and are associated with progression. Female sex, larger tumors, number of prior recurrences, and lack of maintenance BCG were associated with multiple recurrences. Multiple recurrences may prove useful as a clinical trial endpoint for IR-NMIBC.

Smoking Behaviors and Prognosis in Patients With Non-Muscle-Invasive Bladder Cancer in the Be-Well Study.

Importance: Tobacco smoking is an established risk factor associated with bladder cancer, yet its impact on bladder cancer prognosis is unclear. Objective: To examine associations of use of tobacco (cigarettes, pipes, and cigars), e-cigarettes, and marijuana with risk of recurrence and progression of non-muscle-invasive bladder cancer (NMIBC) and to explore use of smoking cessation interventions. Design, Setting, and Participants: The Be-Well Study is a prospective cohort study of patients with NMIBC diagnosed from 2015 to 2019 and followed-up for 26.4 months in the Kaiser Permanente Northern and Southern California integrated health care system. Eligibility criteria were age at least 21 years, first NMIBC diagnosis (stages Ta, Tis, or T1), alive, and not in hospice care. Exclusion criteria were previous diagnosis of bladder cancer or other cancer diagnoses within 1 year prior to or concurrent with NMIBC diagnosis. Data were analyzed from April 1 to October 4, 2022. Exposures: Use of cigarettes, pipes, cigars, e-cigarettes, and marijuana was reported in the baseline interview. Use of smoking cessation interventions (counseling and medications) was derived from electronic health records. Main Outcomes and Measures: Hazard ratios (HRs) and 95% CIs of recurrence and progression of bladder cancer were estimated by multivariable Cox proportional hazards regression. Results: A total of 1472 patients (mean [SD] age at diagnosis, 70.2 [10.8%] years; 1129 [76.7%] male patients) with NMIBC were enrolled at a mean (SD) of 2.3 (1.3) months after diagnosis, including 874 patients (59.4%) who were former smokers and 111 patients (7.5%) who were current cigarette smokers; 67 patients (13.7%) smoked pipes and/or cigars only, 65 patients (4.4%) used e-cigarettes, 363 patients (24.7%) used marijuana. Longer cigarette smoking duration and more pack-years were associated with higher risk of recurrence in a dose-dependent manner, with the highest risks for patients who had smoked for 40 or more years (HR, 2.36; 95% CI, 1.43-3.91) or 40 or more pack-years (HR, 1.97; 95% CI, 1.32-2.95). There was no association of having ever smoked, being a former or current cigarette smoker, and years since quit smoking with recurrence risk. No associations with pipes, cigars, e-cigarettes, or marijuana were found. Of 102 patients offered a smoking cessation intervention, 57 (53.8%) received an interventions after diagnosis, with female patients more likely than male patients to engage in such interventions (23 of 30 female patients [76.7%] vs 34 of 76 male patients [44.7%]; P = .003). Conclusions and Relevance: These findings suggest that longer duration and more pack-years of cigarette smoking were associated with higher risk of NMIBC recurrence. Cigarette smoking remains a critical exposure before and after diagnosis in survivors of NMIBC.

Catheter Balloon-trauma: Design, Development, and Ex-vivo Studies Using Intact Human Penis Specimens.

OBJECTIVE: To present a novel urethral catheter design with a pilot balloon to reduce intraurethral retention balloon inflation pressures and to provide a visual alert during catheter placement. METHODS: We manufactured our pilot balloon prototype from both molded and extruded silicone components. Various pilot balloon thicknesses were tested in order to determine the ideal compliance. We studied the filling pressures of the retention balloon of our prototype in a mechanical urethral model. The prototype catheter was then tested in ex-vivo human penis specimens obtained from gender affirming surgery and changes in the size of the retention balloon were measured under fluoroscopy. RESULTS: The thickness of the pilot balloon was directly related to the inflation pressure of the retention balloon in the mechanical urethral model. The thickness chosen for the pilot balloon in our prototype was based on a retention balloon pressure of 70 kPa. In the ex-vivo human penis model, the presence of the pilot balloon resulted in a 40% reduction in the cross-sectional area of the retention balloon compared to a standard urinary catheter. CONCLUSION: The prototype urinary catheter appears to decrease the filling pressure and size of an improperly positioned retention balloon inside a urethra. This can potentially reduce the risk of iatrogenic urethral catheter injuries. In addition, the prototype urinary catheter may act as a visual warning sign for the healthcare practitioner.

Tighter Blood Pressure Control Is Associated with Lower Incidence of Erectile Dysfunction in Hypertensive Men.

INTRODUCTION: Tighter blood pressure control is widely thought to be associated with better erectile function, although the preponderance of data is limited to dichotomous representations of hypertension without an attempt to look at degree of blood pressure control. AIM: To determine the association between optimal blood pressure control over time and the development of erectile dysfunction (ED) in a cohort of potent men. METHODS: We performed a retrospective cohort study of newly diagnosed hypertensive men without major medical comorbidities in an integrated healthcare system. Patients were stratified by exposure to hypertension, with varying levels of blood pressure control, as measured by ordinal categories of systolic blood pressure and deviation from the mean systolic pressure. MAIN OUTCOME MEASURES: Incidence of ED was defined by at least 2 primary care or urology diagnoses of ED in our electronic health records within 2 years, at least 2 filled prescriptions for ED medications within 2 years, or 1 diagnosis of ED and 2 filled prescriptions for ED medications. RESULTS: We identified 39,320 newly diagnosed hypertensive men. The overall incidence for ED was 13.9%, with a mean follow-up of 55.1 ± 28.7 months. Higher average systolic blood pressure was associated with a higher risk of ED in a dose-dependent manner (trend test, P < .001). Wide variation in blood pressure control was associated with a higher incidence of ED (OR [95% CI]; 1.359 [1.258-1.469]) and a shorter time to the development of ED (log rank, P < .0001). CLINICAL IMPLICATIONS: We believe these data may serve as a motivator for hypertensive men to better adhere to their hypertension treatment regimen. STRENGTH & LIMITATIONS: The retrospective nature of our study precludes us from drawing more than an association between tighter blood pressure control and ED. Strengths of our study include the large sample size, community cohort, and completeness of follow-up. CONCLUSION: Among adults diagnosed with hypertension, tighter blood pressure control, as measured by average systolic blood pressure and deviation from the average, is associated with a lower incidence and a longer time to the development of ED. Hsiao W, Bertsch RA, Hung Y-Y, et al. Tighter Blood Pressure Control Is Associated with Lower Incidence of Erectile Dysfunction in Hypertensive Men. J Sex Med 2019;16:410-417.

The Be-Well Study: a prospective cohort study of lifestyle and genetic factors to reduce the risk of recurrence and progression of non-muscle-invasive bladder cancer.

PURPOSE: Bladder cancer is one of the top five cancers diagnosed in the U.S. with a high recurrence rate, and also one of the most expensive cancers to treat over the life-course. However, there are few observational, prospective studies of bladder cancer survivors. METHODS: The Bladder Cancer Epidemiology, Wellness, and Lifestyle Study (Be-Well Study) is a National Cancer Institute-funded, multi-center prospective cohort study of non-muscle-invasive bladder cancer (NMIBC) patients (Stage Ta, T1, Tis) enrolled from the Kaiser Permanente Northern California (KPNC) and Southern California (KPSC) health care systems, with genotyping and biomarker assays performed at Roswell Park Comprehensive Cancer Center. The goal is to investigate diet and lifestyle factors in recurrence and progression of NMIBC, with genetic profiles considered, and to build a resource for future NMIBC studies. RESULTS: Recruitment began in February 2015. As of 30 June 2018, 1,281 patients completed the baseline interview (774 KPNC, 511 KPSC) with a recruitment rate of 54%, of whom 77% were male and 23% female, and 80% White, 6% Black, 8% Hispanic, 5% Asian, and 2% other race/ethnicity. Most patients were diagnosed with Ta (69%) or T1 (27%) tumors. Urine and blood specimens were collected from 67% and 73% of consented patients at baseline, respectively. To date, 599 and 261 patients have completed the 12- and 24-month follow-up questionnaires, respectively, with additional urine and saliva collection. CONCLUSIONS: The Be-Well Study will be able to answer novel questions related to diet, other lifestyle, and genetic factors and their relationship to recurrence and progression among early-stage bladder cancer patients.

Perioperative Intravesical Chemotherapy for Patients WithNon-Muscle-invasive Bladder Cancer: Understanding the Extent of and Sources of Variation in Guideline-recommended Use.

OBJECTIVE: To examine intravesical chemotherapy (IVC) use according to non-muscle-invasive bladder cancer patient disease risk, and the contributions of multilevel factors to variation in proficient use among patients with low-intermediate disease. METHODS: This study included 988 patients diagnosed with non-muscle-invasive bladder cancer in an integrated health system in Northern California from 2015-2017. We calculated IVC receipt by disease risk, and among patients with low-intermediate risk disease, assessed the relationship between multilevel factors and IVC receipt using a logistic regression model with random intercepts for provider and service area, and patient-, provider-, and service area-level fixed effects. We further assessed the association of provider- and service area-level factors with IVC use by examining intraclass correlation coefficients. RESULTS: Similar proportions of low-intermediate (36%) and high-risk (34%) patients received IVC. In the multivariate analysis, including low-intermediate risk patients, service area volume was strongly and statistically significantly associated with IVC use (adjusted odds ratio, high- vs low-volume: 0.08, 95% Confidence Interval: 0.01-0.58). Provider- and service area-level intraclass correlation coefficients were large, (38%, P = .0009 and 39% P = .03, respectively) indicating that much of the variance in IVC use was explained by factors at these levels. CONCLUSION: Our findings highlight opportunities to improve proficient use of IVC. Future research should assess provider- and practice-level barriers to IVC use among low-intermediate risk patients.

Factors That Influence Selectionof Urinary Diversion Among Bladder Cancer Patients in 3 Community-based Integrated Health Care Systems.

OBJECTIVE: To assess the relative contributions of patient and surgeon factors for predicting selection of ileal conduit (IC), neobladder (NB), or continent pouch (CP) urinary diversions (UD) for patients diagnosed with muscle-invasive/high-risk nonmuscle invasive bladder cancer. This information is needed to enhance research comparing cancer survivors' outcomes across different surgical treatment options. METHODS: Bladder cancer patients' age ≥21 years with cystectomy/UD performed from January 2010 to June 2015 in 3 Kaiser Permanente regions were included. All patient and surgeon data were obtained from electronic health records. A mixed effects logistic regression model was used treating surgeon as a random effect and region as a fixed effect. RESULTS: Of 991 eligible patients, 794 (80%) received IC. One hundred sixty-nine surgeons performed the surgeries and accounted for a sizeable proportion of the variability in patient receipt of UD (intraclass correlation coefficient = 0.26). The multilevel model with only patient factors showed good fit (area under the curve = 0.93, Hosmer-Lemeshow test P = .44), and older age, female sex, estimated glomerular filtration rate <45, 4+ comorbidity index score, and stage III/IV tumors were associated with higher odds of receiving an IC vs neobladder/continent pouch. However, including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) had no association (P = .29). CONCLUSION: In this community setting, patient factors were major predictors of UD received. Surgeons also played a substantial role, yet clinical training and experience were not major predictors. Surgeon factors such as beliefs about UD options and outcomes should be explored.

The Use of 5-Alpha Reductase Inhibitors to Manage Benign Prostatic Hyperplasia and the Risk of All-cause Mortality.

OBJECTIVE: To compare the risk of mortality among men treated for benign prostatic hyperplasia (BPH) with 5 alpha-reductase inhibitors (5ARI) to those treated with alpha-blockers (AB) in community practice settings. METHODS: We employed a retrospective matched cohort study in 4 regions of an integrated healthcare system. Men aged 50 years and older who initiated pharmaceutical treatment for BPH and/or lower urinary tract symptoms between 1992 and 2008 and had at least 3 consecutive prescriptions that were eligible and followed through 2010 (N = 174,895). Adjusted hazard ratios were used to estimate the risk of mortality due to all-causes associated with 5ARI use (with or without concomitant ABs) as compared to AB use. RESULTS: In this large and diverse sample with 543,523 person-years of follow-up, 35,266 men died during the study period, 18.9% of the 5ARI users and 20.4% of the AB users. After adjustment for age, medication initiation year, race, region, prior AB history, Charlson score, and comorbidities, 5ARI use was not associated with an increased risk of mortality when compared to AB use (Adjusted hazard ratios: 0.64, 95% confidence interval: 0.62, 0.66). CONCLUSION: Among men receiving medications for BPH in community practice settings, 5ARI use was not associated with an increased risk of mortality when compared to AB use. These data provide reassurance about the safety of using 5ARIs in general practice to manage BPH and/or lower urinary tract symptoms.

Quality of life among men with low-risk prostate cancer during the first year following diagnosis: the PREPARE prospective cohort study.

As many as 40% of men diagnosed with prostate cancer have low-risk disease, which results in the need to decide whether to undergo active treatment (AT) or active surveillance (AS). The treatment decision can have a significant effect on general and prostate-specific quality of life (QOL). The purpose of this study was to assess the QOL among men with low-risk prostate cancer during the first year following diagnosis. In a prospective cohort study, we conducted pretreatment telephone interviews (N = 1,139; 69.3% response rate) with low-risk PCa patients (PSA ≤ 10, Gleason ≤ 6) and a follow-up assessment 6-10 months postdiagnosis (N = 1057; 93%). We assessed general depression, anxiety, and physical functioning, prostate-specific anxiety, and prostate-specific QOL at both interviews. Clinical variables were obtained from the medical record. Men were 61.7 (SD = 7.2) years old, 82% white, 39% had undergone AT (surgery or radiation), and 61.0% had begun AS. Linear regression analyses revealed that at follow-up, the AS group reported significantly better sexual, bowel, urinary, and general physical function (compared to AT), and no difference in depression. However, the AS group did report greater general anxiety and prostate-specific anxiety at follow-up, compared to AT. Among men with low-risk PCa, adjusting for pretreatment functioning, the AS group reported better prostate-related QOL, but were worse off on general and prostate-specific anxiety compared to men on AT. These results suggest that, within the first year postdiagnosis, men who did not undergo AT may require additional support in order to remain comfortable with this decision and to continue with AS when it is clinically indicated.

Physicians' perspectives on the informational needs of low-risk prostate cancer patients.

Despite the evidence indicating that decision aids (DA) improve informed treatment decision making for prostate cancer (PCa), physicians do not routinely recommend DAs to their patients. We conducted semi-structured interviews with urologists (n = 11), radiation oncologists (n = 12) and primary care physicians (n = 10) about their methods of educating low-risk PCa patients regarding the treatment decision, their concerns about recommending DAs, and the essential content and format considerations that need to be addressed. Physicians stressed the need for providing comprehensive patient education before the treatment decision is made and expressed concern about the current unevaluated information available on the Internet. They made recommendations for a DA that is brief, applicable to diverse populations, and that fully discloses all treatment options (including active surveillance) and their potential side effects. Echoing previous studies showing that low-risk PCa patients are making rapid and potentially uninformed treatment decisions, these results highlight the importance of providing patient education early in the decision-making process. This need may be fulfilled by a treatment DA, should physicians systematically recommend DAs to their patients. Physicians' recommendations for the inclusion of particular content and presentation methods will be important for designing a high quality DA that will be used in clinical practice.

Mortality and Androgen Deprivation Therapy as Salvage Treatment for Biochemical Recurrence after Primary Therapy for Clinically Localized Prostate Cancer.

PURPOSE: Androgen deprivation therapy is often used as salvage treatment in men with rising prostate specific antigen after initial radical prostatectomy or radiotherapy for clinically localized prostate cancer. Given the lack of evidence from general practice, we examined the association of salvage androgen deprivation therapy with mortality in an observational cohort study. MATERIALS AND METHODS: From 3 managed care organizations we assembled a retrospective cohort of all 5,804 men with newly diagnosed localized prostate cancer from 1995 to 2009 who had a prostate specific antigen increase (biochemical recurrence) after primary radical prostatectomy or radiotherapy. The main outcomes were all-cause and prostate cancer specific mortality. We used Cox proportional hazards models to estimate mortality with salvage androgen deprivation therapy as a time dependent predictor. RESULTS: Overall salvage androgen deprivation therapy was not associated with all-cause or prostate cancer specific mortality in the prostatectomy cohort (HR 0.97, 95% CI 0.70-1.35 or HR 1.18, 95% CI 0.68-2.07) or in the radiotherapy cohort (HR 0.84, 95% CI 0.70-1.01 or HR 1.06, 95% CI 0.80-1.40, respectively). Among men with prostate specific antigen doubling time less than 9 months after the prostate specific antigen rise, salvage androgen deprivation therapy was statistically significantly associated with a decreased risk of all-cause and prostate cancer specific mortality in the prostatectomy cohort (HR 0.35, 95% CI 0.20-0.63 and HR 0.43, 95% CI 0.21-0.91) and in the radiotherapy cohort (HR 0.62, 95% CI 0.48-0.80 and HR 0.65, 95% CI 0.47-0.90, respectively). CONCLUSIONS: We found no association of salvage androgen deprivation therapy with all-cause or cause specific mortality in most men with biochemical recurrence after primary radical prostatectomy or radiotherapy for clinically localized prostate cancer. Men with quickly progressed disease may derive a clinical benefit from salvage androgen deprivation therapy.

Use of androgen deprivation therapy as salvage treatment after primary therapy for clinically localized prostate cancer.

PURPOSE: The optimal use of androgen deprivation therapy as salvage treatment (sADT) for men after initial prostatectomy or radiotherapy for clinically localized prostate cancer is undefined. We describe patterns of sADT use and investigate clinical and sociodemographic characteristics of insured men who received sADT versus surveillance in managed care settings. METHODS: Using comprehensive electronic health records and cancer registry data from three integrated health plans, we identified all men with newly diagnosed clinically localized prostate cancer between 1995 and 2009 who received either prostatectomy (n = 16,445) or radiotherapy (n = 19,531) as their primary therapy. We defined sADT based on the timing of ADT following primary therapy and stage of cancer. We fit Cox proportional hazard models to identify sociodemographic characteristics and clinical factors associated with sADT. RESULTS: With a median follow-up of 6 years (range 2-15 years), 13 % of men who underwent primary prostatectomy or radiotherapy received sADT. After adjusting for selected covariates, sADT was more likely to be used in men who were older (e.g., HR 1.70, 95 % CI 1.48-1.96 or HR 1.33, 95 % CI 1.17-1.52 for age 70+ relative to age 35-59 for primary prostatectomy or radiotherapy, respectively), were African-American, had a short PSA doubling time, had a higher pre-treatment risk of progression, had more comorbidities, and received adjuvant ADT for initial disease. CONCLUSIONS: In men with localized prostate cancer in community practice initially treated with prostatectomy or radiotherapy, sADT after primary treatment was more frequent for men at greater risk of death from prostate cancer, consistent with practice guidelines.

Sociodemographic and Clinical Predictors of Switching to Active Treatment among a Large, Ethnically Diverse Cohort of Men with Low Risk Prostate Cancer on Observational Management.

PURPOSE: We determined the clinical and sociodemographic predictors of beginning active treatment in an ethnically diverse population of men with low risk prostate cancer initially on observational treatment. MATERIALS AND METHODS: We retrospectively studied men diagnosed with low risk prostate cancer between 2004 and 2012 at Kaiser Permanente Northern California who did not receive any treatment within the first year of diagnosis and had at least 2 years of followup. We used Cox proportional hazards regression models to determine factors associated with time from diagnosis to active treatment. RESULTS: We identified 2,228 eligible men who were initially on observation, of whom 27% began active treatment during followup at a median of 2.9 years. NonHispanic black men were marginally more likely to begin active treatment than nonHispanic white men independent of baseline and followup clinical measures (HR 1.3, 95% CI 1.0-1.7). Among men who remained on observation nonHispanic black men were rebiopsied within 24 months of diagnosis at a slightly lower rate than nonHispanic white men (HR 0.70, 95% CI 0.6-1.0). Gleason grade progression (HR 3.3, 95% CI 2.7-4.1) and PSA doubling time less than 48 months (HR 2.9, 95% CI 2.3-3.7) were associated with initiation of active treatment independent of race. CONCLUSIONS: Sociodemographic factors such as ethnicity and education may independently influence the patient decision to pursue active treatment and serial biopsies during active surveillance. These factors are important for further studies of prostate cancer treatment decision making.

5-Alpha Reductase Inhibitors and the Risk of Prostate Cancer Mortality in Men Treated for Benign Prostatic Hyperplasia.

OBJECTIVE: To compare the risk of prostate cancer mortality among men treated with 5- alpha reductase inhibitors (5-ARIs) with those treated with alpha-adrenergic blockers (ABs) in community practice settings. PATIENTS AND METHODS: A retrospective matched cohort (N=174,895) and nested case-control study (N=18,311) were conducted in 4 regions of an integrated health care system. Men 50 years and older who initiated pharmaceutical treatment for benign prostatic hyperplasia between January 1, 1992, and December 31, 2007, and had at least 3 consecutive prescriptions were followed through December 31, 2010. Adjusted subdistribution hazard ratios, accounting for competing risks of death, and matched odds ratios were used to estimate prostate cancer mortality associated with 5-ARI use (with or without concomitant ABs) as compared with AB use. RESULTS: In the cohort study, 1,053 men died of prostate cancer (mean follow-up, 3 years), 15% among 5-ARI users (N= 25,388) and 85% among AB users (N=149,507) (unadjusted mortality rate ratio, 0.80). After accounting for competing risks, it was found that 5-ARI use was not associated with prostate cancer mortality when compared with AB use (adjusted subdistribution hazard ratio, 0.85; 95% CI, 0.72-1.01). Similar results were observed in the case-control study (adjusted matched odds ratio, 0.95; 95% CI, 0.78-1.17). CONCLUSION: Among men being pharmaceutically treated for benign prostatic hyperplasia, 5-ARI use was not associated with an increased risk of prostate cancer-specific mortality when compared with AB use. The increased prevalence of high-grade lesions at the time of diagnosis noted in our study and the chemoprevention trials may not result in increased prostate cancer mortality.