The Lowest PSA Level Achieved Before CRPC Predicts Abiraterone Response But Not Enzalutamide Response in Metastatic CRPC

Background This study aimed to clarify whether variations in the lowest prostate‑specific antigen (PSA) level prior to the development of castration‑resistant prostate cancer (CRPC) influence the efficacy of subsequent enzalutamide (ENZ) or abiraterone plus prednisolone (ABI) therapy in metastatic CRPC. Methods Using data from the ENABLE study, an investigator‑initiated, multicenter, randomized controlled trial, patients were retrospectively categorized into two groups based on the lowest PSA level prior to metastatic CRPC development: ≤ 0.05 ng/mL (low group) and > 0.05 ng/mL (high group). Endpoints included time to PSA progression (TTPP), radiographic progression‑free survival (rPFS), docetaxel‑free survival (DFS), and overall survival (OS) in the overall study population and within the ABI and ENZ treatment arms. Results A total of 39 and 94 patients were classified into the low and high groups, respectively. In the overall population, survival outcomes did not differ significantly between the groups except for DFS (median 29.0 vs. 15.2 months, p = 0.0209). In the ABI arm (low group, n = 15; high group, n = 45), median TTPP, rPFS, DFS, and OS were undefined versus 4.7 months, 39.5 versus 9.8 months, 29.0 versus 14.0 months, and undefined versus 33.3 months in the low and high groups, respectively ( p = 0.0443, p = 0.0243 p = 0.0106, and p = 0.0319). In contrast, in the ENZ arm (low group, n = 24; high group, n = 49), no significant differences were observed in any endpoint between the two groups. Conclusions The findings of this study indicate that the lowest PSA level prior to CRPC onset may have a potential association with outcomes following subsequent ABI therapy, whereas no such trend was observed for ENZ in metastatic CRPC.