An exploratory retrospective multicenter study of prognostic factors in mCRPC patients undergoing enzalutamide treatment: Focus on early PSA decline and kinetics at time of progression

Background Recent studies have shown that an early prostate-specific antigen (PSA) response to androgen receptor-targeting agents in metastatic castration-resistant prostate cancer (mCRPC) is associated with a better prognosis. We analyzed the early PSA response to enzalutamide (ENZ) by measuring the PSA doubling time (PSADT) and PSA velocity (PSAV) while monitoring oncologic outcomes and survival in Japanese patients. Methods We analyzed a total of 241 patients with mCRPC who were treated with ENZ. The patients' median age was 75 +/- 7.9 years (range, 53-93 years). There were 171 (71%) predocetaxel cases, and 70 (29%) post docetaxel cases. PSA-progression-free survival (PFS) and overall survival (OS) were assessed according to Prostate Cancer Working Group 2 criteria. This study was approved by the Institutional Review Board of Gunma University Hospital (No. 1595). Results We observed 77 good response (GR; case in which PSA remained low after treatment) cases (31.9%), 125 acquired resistance (AR; decline in PSA after treatment followed by progression) cases (51.9%), and 39 primary resistance (PR; lack of decline in PSA) cases (16.2%). Predocetaxel, PSA-PFS, and OS were significantly higher compared with post docetaxel (PSA-PFS: 47.0 vs 13.4 weeks, P < .001; OS: not yet reached vs 80.7 weeks, P < .001). Multivariate analysis of prognostic factors, including PSA response at 4 weeks, was performed using Cox regression analysis. ECOG PS (0 vs 1-2), hemoglobin (Hb; >= 12.2 vs < 12.2 g/dL), time to CRPC ( >= 12 vs < 12 m), docetaxel treatment history (no vs yes), and a PSA reduction of 50% at 4 weeks were significant predictors of OS (all, P < .05). In cases of AR (n = 125), multivariate analysis showed that PSA kinetic factors, such as PSADT and PSAV (ng/mL/m), Hb, time to CRPC, PSADT ( >= 2 vs < 2 m), and PSAV ( < 20 vs >= 20 ng/mL/m), were all predictive of OS following PSA-progression (P < .05). Conclusions Our study has demonstrated that PSA dynamics after ENZ administration may be a useful prognostic factor for mCRPC patients.