Survival Benefit of ARSI Therapy in Japanese mCSPC: A Systematic Review and Meta-Analysis.

Abstract

Randomized clinical trials have shown that second-generation androgen receptor signaling inhibitors (ARSIs) improve overall survival (OS) in metastatic castration-sensitive prostate cancer (mCSPC). In Japan, combined androgen blockade (CAB) has been widely used as conventional hormonal therapy, unlike Western trials in which androgen deprivation therapy (ADT) alone was the primary comparator. Whether this treatment context influences the survival benefit of ARSI-based therapy in Japanese clinical practice remains uncertain. We conducted a systematic review and meta-analysis of studies evaluating ARSI plus ADT versus conventional hormonal therapy (ADT alone or CAB) in Japanese patients with mCSPC. PubMed and Ichushi-Web were searched through February 2026. Adjusted hazard ratios from multivariable or propensity score-matched analyses were pooled using a random-effects model. Risk of bias was assessed using ROBINS-I. Fourteen studies were included. Eleven all-comer mCSPC cohorts were included in the primary analysis. ARSI-based therapy was associated with improved OS compared with conventional hormonal therapy (pooled hazard ratio 0.86, 95% confidence interval 0.77-0.96), with no heterogeneity (I² = 0%). The prediction interval was 0.76 to 0.98. Sensitivity and subgroup analyses, including CAB-based comparator cohorts, showed consistent results. ARSI-based therapy was associated with a modest but consistent improvement in OS in Japanese mCSPC. The attenuated effect size compared with randomized trials may reflect multiple factors, including differences in baseline treatment strategies, subsequent therapies, healthcare systems, and study design. These findings highlight the importance of treatment context when interpreting randomized trial evidence. This systematic review and meta-analysis was conducted in accordance with the PRISMA 2020 statement and was registered in PROSPERO (registration number: CRD420261380244).