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.