Sequential Treatment and Survival Outcomes According to Abiraterone Timing in High-Risk mHSPC: A Real-World Propensity-Matched Study

Background The optimal timing of abiraterone acetate (AA) in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC) remains unclear. Unlike previous studies comparing upfront AA with combined androgen blockade (CAB) or androgen deprivation therapy (ADT) alone, our study uniquely focused on patients who received AA at some point during their treatment. We aimed to evaluate whether the timing of AA administration influences cancer-specific survival (CSS), with particular attention to outcomes following progression to castration-resistant prostate cancer (CRPC). Methods This retrospective study included 209 patients with high-risk mHSPC treated at two institutions between 2015 and 2022. All patients received AA during their treatment course. Patients were classified into upfront AA and AA after CRPC groups. Propensity score matching (1:1) was performed using age, PSA, ALP, LDH, hemoglobin, Gleason score, extent of disease (EOD) score, and visceral metastases. The primary endpoint was CSS. Kaplan–Meier analysis and Cox regression were used to compare outcomes. Results After matching, 85 patients were included in each group. The upfront AA group had a significantly longer time to CRPC (median not reached vs. 12.1 months; P < 0.001). However, no significant difference in CSS was observed between groups (P = 0.279). Importantly, CSS after CRPC was significantly shorter in the upfront AA group (median 17.6 vs. 50.4 months; P < 0.001). The upfront AA group also received fewer sequential therapies after CRPC progression. These findings suggest that upfront AA alone does not improve long-term survival and may limit subsequent treatment options. Conclusions While upfront AA prolongs time to CRPC, it does not translate into improved CSS. Our results highlight the need to optimize treatment sequencing for patients with CRPC following upfront androgen receptor signaling inhibitor use and suggest that alternative post-CRPC strategies should be considered to enhance survival.