Real-world Comparative Study of Androgen Receptor Signaling Inhibitors in Japanese Patients With Non-metastatic Castration-resistant Prostate Cancer.

BACKGROUND/AIM: Androgen receptor signaling inhibitors (ARSIs) are widely used for non-metastatic castration-resistant prostate cancer (nmCRPC). However, real-world data comparing clinical outcomes and treatment persistence among ARSIs in Asian populations remain limited. This study aimed to evaluate real-world effectiveness and tolerability of ARSIs in Japanese patients with nmCRPC.

PATIENTS AND METHODS: We retrospectively reviewed 100 Japanese patients with nmCRPC treated with enzalutamide (ENZ), apalutamide (APA), or darolutamide (DARO) at Kansai Medical University and its affiliated hospitals between May 2020 and December 2024. Progression-free survival (PFS), overall survival (OS), prostate-specific antigen (PSA) response, treatment sequencing, and adverse event-related dose modification or discontinuation were analyzed using Kaplan-Meier and log-rank tests.

RESULTS: The median PFS for the entire cohort was 21.5 months. ENZ showed significantly longer PFS compared with APA (p=0.03), while DARO demonstrated comparable outcomes to both agents. OS did not differ significantly among groups. Patients receiving ARSI as first-line therapy had significantly longer PFS than those treated with second-line ARSIs. Initiation of ARSI therapy at PSA levels <2.0 ng/ml was associated with improved PFS. Second-line ARSI therapy showed limited PSA response and shorter PFS. Adverse event-related dose reduction or treatment discontinuation was associated with poorer PFS, with dermatologic toxicity being the main cause of APA discontinuation.

CONCLUSION: In Japanese real-world practice, ARSI effectiveness in nmCRPC appears influenced by treatment persistence, timing of initiation, and treatment sequencing. Early initiation and careful management of adverse events may optimize outcomes, whereas sequential ARSI use shows limited benefit.