Real-world outcomes of prostate-specific membrane antigen-targeted radioligand therapy in Japanese patients with metastatic castration-resistant prostate cancer

Abstract

Purpose: Prostate-specific membrane antigen radioligand therapy (PSMA RLT) improves survival in metastatic castration-resistant prostate cancer (mCRPC). However, evidence in Japanese cohorts is limited. We evaluated the safety and efficacy of PSMA RLT in Japanese patients with mCRPC. Materials and Methods: We retrospectively analyzed 82 Japanese patients with mCRPC treated with PSMA RLT between 2018 and 2024 in Australia. PSMA RLT included Lutetium-177, Actinium-225, or Terbium-161 conjugated PSMA ligands, following PSMA Positron Emission Tomography / Computed Tomography confirmation of target expression. Endpoints were prostate-specific antigen (PSA) response (≥50% decline), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TrAEs). Cox proportional hazards regression identified prognostic factors for survival. Results: Thirty-one patients (38%) achieved a PSA response. Median PFS and OS were 4 and 20 months, respectively. While no significant difference was observed in >50% PSA decline, >80% decline was significantly higher in chemo-naïve patients (43% vs. 7.4%, P < .001), with longer PFS (8 vs. 3 months, P = .006) and OS (not reached vs. 11 months, P < .001). On multivariable analysis, poorer performance status and prior chemotherapy were independent factors for worse OS. TrAEs of any grade occurred in 49 patients (60%), most commonly fatigue. Grade ≥ 3 TrAEs occurred in 15%, with no treatment-related deaths. Conclusion: PSMA RLT provided meaningful clinical benefit with favorable tolerability in Japanese patients with mCRPC, especially those without prior chemotherapy. Early integration of PSMA RLT may offer additional therapeutic advantages.