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Background: LATITUDE was the first phase 3 trial examining the survival benefit of adding abiraterone acetate (AA) + prednisone (P) to androgen-deprivation therapy (ADT) in newly diagnosed metastatic, castration-sensitive prostate cancer (mCSPC). Due to significant improvement in overall survival after the first interim analysis, patients in the placebos + ADT arm could switch to AA + P + ADT during an open-label extension. As in other studies where switching is allowed, statistical adjustments are needed to assess the real benefit of new drugs., Patients and Methods: This was a post hoc analysis to estimate the true survival benefit of AA + P + ADT in patients with newly diagnosed mCSPC by applying statistical adjustments commonly used to adjust for treatment switching., Results: Of 112 patients still receiving placebos + ADT at the first interim analysis, 72 switched to AA + P + ADT during the open-label extension. Final analysis was conducted after median follow-up of 51.8 months. Compared to the placebos + ADT arm, the risk of death in the AA + P + ADT arm was 34% lower [hazard ratio (HR) = 0.663 (95% confidence interval 0.566-0.778)] by unadjusted intent-to-treat analysis, 37% lower [HR = 0.629 (95% confidence interval 0.526-0.753)] by rank preserving structure failure time modeling, and 38% lower [HR = 0.616 (95% confidence interval 0.524-0.724)] by inverse probability of censoring weights., Conclusions: Analyses adjusting for treatment switching using two different statistical approaches confirm the improved survival benefit of adding AA + P to ADT in patients with newly diagnosed mCSPC., Trial Registration: ClinicalTrials.gov identifier NCT01715285.

Background: Enzalutamide and abiraterone acetate plus prednisone, which target the androgen receptor axis, have expanded the treatment of advanced prostate cancer. Retrospective analyses suggest some cross-resistance between these two drugs when used sequentially, but robust, prospective studies have not yet been reported., Objective: To fulfil a regulatory postregistration commitment by evaluating the efficacy and safety of enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who progressed following abiraterone acetate plus prednisone treatment., Design, Setting, and Participants: Multicentre, single-arm, open-label study, enrolled patients with progressing mCRPC after ≥24 wk of abiraterone acetate plus prednisone treatment. All patients maintained castration therapy during the trial. Prior chemotherapy was allowed but not required., Intervention: Patients received enzalutamide 160mg/d orally., Outcome Measurements and Statistical Analysis: The primary endpoint was radiographic progression-free survival. Secondary endpoints were overall survival, prostate-specific antigen (PSA) response, and time-to-PSA progression. Safety data were also assessed. Kaplan-Meier methods were used to descriptively analyse time-to-event endpoints., Results and Limitations: Overall, 214 patients received enzalutamide treatment, 145 of whom were chemotherapy-naïve. Median radiographic progression-free survival was 8.1 mo (95% confidence interval: 6.1-8.3); median overall survival had not been reached. Unconfirmed PSA response rate was 27% (48 of 181). Median time-to-PSA progression was 5.7 mo (95% confidence interval: 5.6-5.8). The most common treatment-emergent adverse events were fatigue (32%), decreased appetite (25%), asthenia (18%), back pain (17%), and arthralgia (16%). No seizures were reported., Conclusions: Enzalutamide showed antitumour activity in some patients with mCRPC who had previously progressed following ≥24 wk of abiraterone acetate plus prednisone treatment., Patient Summary: Patients with mCRPC who progressed on previous abiraterone acetate plus prednisone treatment, with or without prior chemotherapy, received enzalutamide. Although cross-resistance between the two agents was observed in a majority of patients, some still benefited from enzalutamide treatment., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Background: The Prostate CAncer gene 3 (PCA3) assay has shown promise as an aid in prostate cancer (pCA) diagnosis in identifying men with a high probability of a positive (repeat) biopsy., Objective: This study evaluated the clinical utility of the PROGENSA PCA3 assay., Design, Setting, and Participants: This European prospective, multicentre study enrolled men with one or two negative biopsies scheduled for repeat biopsy., Measurements: After digital rectal examination (DRE), first-catch urine was collected to measure PCA3 mRNA concentration and to calculate the PCA3 score. The PCA3 score was compared to biopsy outcome. The diagnostic accuracy of the PCA3 assay was compared to percent of free prostate-specific antigen (%fPSA)., Results and Limitations: In 463 men, the positive repeat biopsy rate was 28%. The higher the PCA3 score, the greater the probability of a positive repeat biopsy. The PCA3 score (cut-off of 35) had a greater diagnostic accuracy than %fPSA (cut-off of 25%). The PCA3 score was independent of the number of previous biopsies, age, prostate volume, and total prostate-specific antigen (PSA) level. Moreover, the PCA3 score was significantly higher in men with high-grade prostate intraepithelial neoplasia (HGPIN) versus those without HGPIN, clinical stage T2 versus T1, Gleason score >or=7 versus <7, and "significant" versus "indolent" (clinical stage T1c, PSA density [PSAD] <0.15ng/ml, Gleason score in biopsy