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Background: Retrospective analyses of randomized trials suggest that Black men with metastatic castration‐resistant prostate cancer (mCRPC) have longer survival than White men. The authors conducted a prospective study of abiraterone acetate plus prednisone to explore outcomes by race. Methods: This race‐stratified, multicenter study estimated radiographic progression‐free survival (rPFS) in Black and White men with mCRPC. Secondary end points included prostate‐specific antigen (PSA) kinetics, overall survival (OS), and safety. Exploratory analysis included genome‐wide genotyping to identify single nucleotide polymorphisms associated with progression in a model incorporating genetic ancestry. One hundred patients self‐identified as White (n = 50) or Black (n = 50) were enrolled. Eligibility criteria were modified to facilitate the enrollment of individual Black patients. Results: The median rPFS for Black and White patients was 16.6 and 16.8 months, respectively; their times to PSA progression (TTP) were 16.6 and 11.5 months, respectively; and their OS was 35.9 and 35.7 months, respectively. Estimated rates of PSA decline by ≥50% in Black and White patients were 74% and 66%, respectively; and PSA declines to <0.2 ng/mL were 26% and 10%, respectively. Rates of grade 3 and 4 hypertension, hypokalemia, and hyperglycemia were higher in Black men. Conclusions: Multicenter prospective studies by race are feasible in men with mCRPC but require less restrictive eligibility. Despite higher comorbidity rates, Black patients demonstrated rPFS and OS similar to those of White patients and trended toward greater TTP and PSA declines, consistent with retrospective reports. Importantly, Black men may have higher side‐effect rates than White men. This exploratory genome‐wide analysis of TTP identified a possible candidate marker of ancestry‐dependent treatment outcomes. This is the first prospective, race‐stratified study in advanced prostate cancer demonstrating important trends in outcomes previously only observed in retrospective reports. These results demonstrate the feasibility of this approach in a multicenter setting and establish important preliminary data with regard to differences in toxicity profiles and predictive biomarkers by race. [ABSTRACT FROM AUTHOR]

Background: The large registry, PROVENGE Registry for the Observation, Collection, and Evaluation of Experience Data (PROCEED)(NCT01306890), evaluated sipuleucel-T immunotherapy for asymptomatic/minimally symptomatic metastatic castration-resistant prostate cancer (mCRPC).Methods: PROCEED enrolled patients with mCRPC receiving 3 biweekly sipuleucel-T infusions. Assessments included overall survival (OS), serious adverse events (SAEs), cerebrovascular events (CVEs), and anticancer interventions (ACIs). Follow-up was for ≥3 years or until death or study withdrawal.Results: In 2011-2017, 1976 patients were followed for 46.6 months (median). The median age was 72 years, and the baseline median prostate-specific antigen level was 15.0 ng/mL; 86.7% were white, and 11.6% were African American. Among the patients, 1902 had 1 or more sipuleucel-T infusions. The median OS was 30.7 months (95% confidence interval [CI], 28.6-32.2 months). Known prognostic factors were independently associated with OS in a multivariable analysis. Among the 1255 patients who died, 964 (76.8%) died of prostate cancer (PC) progression. The median time from the first infusion to PC death was 42.7 months (95% CI, 39.4-46.2 months). The incidence of sipuleucel-T-related SAEs was 3.9%. The incidence of CVEs was 2.8%, and the rate per 100 person-years was 1.2 (95% CI, 0.9-1.6). The CVE incidence among 11,972 patients with mCRPC from the Surveillance, Epidemiology, and End Results-Medicare database was 2.8%; the rate per 100 person-years was 1.5 (95% CI, 1.4-1.7). One or more ACIs (abiraterone, enzalutamide, docetaxel, cabazitaxel, or radium 223) were received by 77.1% of the patients after sipuleucel-T; 32.5% and 17.4% of the patients experienced 1- and 2-year treatment-free intervals, respectively.Conclusions: PROCEED provides contemporary survival data for sipuleucel-T-treated men in a real-world setting of new life-prolonging agents, which will be useful in discussing treatment options with patients and in powering future trials with sipuleucel-T. The safety and tolerability of sipuleucel-T in PROCEED were consistent with previous findings. [ABSTRACT FROM AUTHOR]

For decades, the management of patients with advanced prostate cancer has been hormonal therapy, known as androgen deprivation therapy, which is intended to lower testosterone levels. Further incremental progress in the treatment of men with metastatic hormone‐sensitive prostate cancer (mHSPC) has come from the addition of docetaxel or abiraterone acetate to androgen deprivation therapy for more aggressive upfront treatment regimens. Other combinatorial regimens testing the addition of novel therapies currently are in the late stages of development and are expected to further improve the clinical outcomes of these patients. The emergence of new positron emission tomography tracers specifically for prostate cancer, particularly prostate‐specific membrane antigen and fluciclovine, has increased the ability to detect metastatic disease earlier in the course of the disease and has helped to describe a new group of patients with mHSPC and oligometastatic disease. For this group of patients with mHSPC, the authors discuss the existing data with metastasis‐directed therapy and primary tumor‐directed therapy. Progress in the treatment of men with metastatic hormone‐sensitive prostate cancer has come from the addition of docetaxel or abiraterone acetate to androgen deprivation therapy for more aggressive upfront treatment regimens. Other combinatorial regimens currently are in the late stages of development and are expected to further improve the clinical outcomes of these patients. The emergence of new positron emission tomography tracers has helped to diagnose metastatic hormone‐sensitive prostate cancer with oligometastases, for which the authors discuss the existing data with metastasis‐directed therapy and primary tumor‐directed therapy. [ABSTRACT FROM AUTHOR]

BACKGROUND Breast cancer 2 ( BRCA2)-associated breast and ovarian cancers are sensitive to platinum-based chemotherapy. It is unknown whether BRCA2-associated prostate cancer responds favorably to such treatment. METHODS A retrospective analysis of a single-institution cohort of men with castration-resistant, metastatic prostate cancer was performed to determine the association between carrier status of pathogenic BRCA2 germline variants and prostate-specific antigen response to carboplatin-based chemotherapy. From 2001 through 2015, 8081 adult men with prostate cancer who had a consultation and/or underwent treatment at Dana-Farber Cancer Institute provided blood samples and consented to analyses of biologic material and clinical records. A subgroup of 141 men received at least 2 doses of carboplatin and docetaxel for castration-resistant disease (94% were also taxane refractory). These patients were categorized according to the absence or presence of pathogenic germline mutations in BRCA2 based on DNA sequencing from whole blood. The primary outcome was the response rate to carboplatin/docetaxel chemotherapy, defined according to a decline in prostate-specific antigen that exceeded 50% within 12 weeks of initiating this regimen. Associations between BRCA2 mutation status and response to carboplatin-based chemotherapy were tested using the Fisher exact test, with a 2-sided P value < .05 as the threshold for significance. RESULTS Pathogenic germline BRCA2 variants were observed in 8 of 141 men (5.7%; 95% confidence interval, 2.5%-10.9%). Six of 8 BRCA2 carriers (75%) experienced prostate-specific antigen declines >50% within 12 weeks, compared with 23 of 133 noncarriers (17%; absolute difference, 58%; 95% confidence interval, 27%-88%; P < .001). Prostate cancer cell lines functionally corroborated these clinical findings. CONCLUSIONS BRCA2-associated, castration-resistant prostate cancer is associated with a higher likelihood of response to carboplatin-based chemotherapy than non- BRCA2-associated prostate cancer. Cancer 2017;123:3532-9. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

What's known on the subject? and What does the study add? The interplay between urologists and oncologists in the treatment of prostate cancer has been long standing. Recent paradigm shifts in treatment are reviewed with an emphasis on how these treatments may eventually alter the dynamic equilibrium between urology and oncology specialists. The treatment landscape for men with castration-resistant prostate cancer (CRPC) is undergoing significant changes; a redefinition of the respective roles of oncologists and urologists will probably occur. In addition, the advent of the multidisciplinary team or coordinated-care approach, which has been gathering momentum over the last decade, will become not simply a preference but a clear necessity. In the present review, we explore the current wave of new treatments and describe the possibility of more complex approaches to combined therapy. New treatment options include abiraterone acetate, cabazitaxel, MDV3100 (in development), radium-223 (in development) and sipuleucel-T. We also present the traditional roles of the urologist and oncologist in caring for patients with CRPC and discuss how these may change. Compounding the new potential for treatment success, as well as the complexity of therapeutic strategies, is the emergence of novel biomarkers to evaluate treatment efficacy and to assist in patient prognosis. The prospects for successful treatment of patients with CRPC have developed considerably so that these patients may soon have a reasonable expectation of therapeutic efficacy and meaningful extension of their lives. [ABSTRACT FROM AUTHOR]

Background: Antiandrogen withdrawal is a potential therapeutic maneuver for patients with progressive prostate cancer. This study was designed to examine antiandrogen withdrawal effects within the context of a large multi-institutional prospective trial.Methods: Eligibility criteria included progressive prostate adenocarcinoma despite combined androgen blockade. Eligible patients received prior initial treatment with an antiandrogen plus orchiectomy or luteinizing hormone-releasing hormone (LHRH) agonist. Patients were stratified according to type of antiandrogen, type of progression (prostate-specific antigen [PSA] or radiographic), presence or absence of metastatic disease, and prior LHRH agonist versus surgical castration.Results: A total of 210 eligible and evaluable patients had a median follow-up of 5.0 years; 64% of patients previously received flutamide, 32% bicalutamide, and 3% nilutamide. Of the 210 patients, 21% of patients had confirmed PSA decreases of >or=50% (95% CI, 16% to 27%). No radiographic responses were recorded. Median progression-free survival (PFS) was 3 months (95% CI, 2 months to 4 months); however, 19% had 12-month or greater progression-free intervals. Median overall survival (OS) after antiandrogen withdrawal was 22 months (20 and 40 months for those with and without radiographic evidence of metastatic disease, respectively). Multivariate analyses indicated that longer duration of antiandrogen use, lower PSA at baseline, and PSA-only progression at study entry were associated with both longer PFS and OS. Longer antiandrogen use was the only significant predictor of PSA response.Conclusions: These data indicate a relatively modest rate of PSA response in patients who were undergoing antiandrogen withdrawal; however, PFS can be relatively prolonged (>or=1 year) in approximately 19% of patients. [ABSTRACT FROM AUTHOR]