Real‐World Comparative Study of Apalutamide Versus Bicalutamide in Combination With Androgen Deprivation Therapy for Metastatic Hormone‐Sensitive Prostate Cancer

ABSTRACT Objectives To evaluate the real‐world effectiveness and safety of apalutamide versus bicalutamide in combination with androgen deprivation therapy (ADT) for metastatic hormone‐sensitive prostate cancer (mHSPC) in Japanese clinical practice. Methods This multicenter retrospective study analyzed 477 patients with mHSPC who received either apalutamide ( n  = 102) or bicalutamide ( n  = 375) in combination with ADT across 19 Japanese institutions. The primary outcome was time to castration‐resistant prostate cancer (CRPC). Secondary outcomes included overall survival (OS), prostate‐specific antigen (PSA) response, and adverse events. Results The apalutamide group showed significantly higher CRPC‐free probability at 24 months (68.2% vs. 39.8%, p  < 0.001) compared to the bicalutamide group. While OS was similar between groups, the apalutamide group demonstrated superior PSA response at 3 months (median PSA: 0.8 vs. 3.4 ng/mL) and lower requirement for secondary treatment (36.3% vs. 53.9%, p  = 0.002). Adverse events were more frequent in the apalutamide group (30.4% vs. 4.3%, p  < 0.001), particularly rash (15.7% vs. 0.3%, p  < 0.001). Conclusions In real‐world Japanese clinical practice, apalutamide demonstrated superior efficacy in delaying progression to CRPC compared to bicalutamide when combined with ADT for mHSPC, with manageable safety profiles.