Radium-223 Treatment Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer: A Taiwan-Japan Collaborative Cohort Study

BACKGROUND: This study examined oncologic outcomes associated with Radium-223 (Ra-223) administered at different treatment lines in patients with metastatic castration-resistant prostate cancer (mCRPC) with bone metastases, and evaluated the prognostic implications of biomarker responses-particularly prostate-specific antigen (PSA) and alkaline phosphatase (ALP)-during Ra-223 therapy. MATERIAL AND METHODS: Patients with mCRPC treated with Ra-223 between August 2016 and March 2023 were identified from the multi-institutional Chang Gung Research Database (Taiwan) and Hirosaki University Hospital (Aomori, Japan). The primary endpoint was the changes in biomarkers during Ra-223 treatment. Secondary endpoints included hematologic adverse events and survival outcomes. Multivariable Cox regression and sensitivity analyses were performed to adjust for baseline clinical factors and potential selection bias. RESULTS: Among 306 included patients, earlier use of Ra-223 was associated with more favorable biomarker dynamics, including smaller post-treatment PSA increase and greater ALP reductions (p=0.003). Post-treatment PSA velocity was significantly lower, and post-Ra-223 survival was longer (both p<0.001), particularly in patients with ALP decreases or PSA increases <100% after Ra-223 treatment (p<0.01), corresponding to survival risk levels (low, intermediate, high). Although overall survival from mCRPC diagnosis differed by treatment line, survival from Ra-223 initiation was more strongly associated with biomarker dynamics than treatment line itself. CONCLUSIONS: In this multicenter cohort, earlier use of Ra-223 in patients with mCRPC was associated with more favorable biomarker responses (PSA and ALP) and longer post-treatment survival. Decreases in ALP levels and limited PSA increases (<100%) were associated with distinct overall and post-treatment survival risk profiles and may serve as clinically useful prognostic indicators.