Clinical benefits of androgen receptor signaling inhibitors in patients with metastatic hormone-sensitive prostate cancer: real-world data from a multi-center study.

Background: This study investigated clinical benefits of androgen receptor signaling inhibitor (ARSI) in patients with synchronous metastatic hormone-sensitive prostate cancer (mHSPC) based on real-world data from multiple centers.

Methods: Clinical records of 1107 mHSPC patients who commenced vintage (bicalutamide) (n = 801) or ARSI (n = 306) treatment in addition to androgen deprivation therapy between 1999 and 2024 were reviewed. Progression-free and overall survival (OS) were examined, and prognostic factors were analyzed using multivariate cox proportional hazard modeling. Propensity score matching (PSM) analysis was performed to balance background characteristics.

Results: Median age and initial prostate-specific antigen level were 73 years and 229 ng/ml, respectively. Kaplan-Meier analysis revealed that upfront ARSI treatment was associated with longer progression-free survival (P < 0.0001, hazard ratio [HR] = 0.37) and OS (P = 0.0088, HR = 0.58) than combined androgen blockade after PSM analysis. In particular, an OS benefit of upfront ARSI was observed in high-volume patients (P = 0.0052, HR = 0.56). ARSI use after castration-resistant prostate cancer (CRPC) development correlated with improved OS as compared to patients without ARSI use (P < 0.0001, HR = 0.52). Multivariate analysis identified ARSI therapy as an independent prognostic factor for OS both when used upfront (P = 0.0141, HR = 0.61) and after CRPC development (P < 0.0001, HR = 0.55). In addition, categorizing all patients into groups receiving no ARSI, ARSI after CRPC, or ARSI as upfront therapy revealed 5-year OS rates of 55.65%, 59.85%, and 65.01%, respectively.

Conclusions: Early use of ARSI in Japanese patients with mHSPC appears clinically beneficial. Our findings suggest the prognostic importance for optimal treatment intensification.