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

Hao Lun Luo; Yi Yang Liu; Hui Ying Liu; Yu Li Su; Yen-Hao Chen; Chikara Ohyama; Shingo Hatakeyama; Hideo Kawaguch; Masahiko Aoki; Yen-Hsiang Chang; Hung-Jen Wang; Yen Ta Chen; Yen Ting Wu; Yin Lun Chang

doi:10.1016/j.bj.2026.100976

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

Biomed J. 2026 Apr 10:100976. doi: 10.1016/j.bj.2026.100976. Online ahead of print.

Authors

Affiliations

¹ Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
² Department of Hematology and Oncology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
³ Department of Urology, Hirosaki University Graduate of Medicine, Hirosaki, Japan.
⁴ Department of Urology, Hirosaki University Graduate of Medicine, Hirosaki, Japan; Department of Advanced Blood Purification Therapy, Hirosaki University Graduate of Medicine, Hirosaki, Japan.
⁵ Department of Radiation Oncology, Hirosaki University Graduate of Medicine, Hirosaki, Japan.
⁶ Nuclear Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan.
⁷ Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan. Electronic address: alesy1980@gmail.com.

PMID: 41967770
DOI: 10.1016/j.bj.2026.100976

Abstract

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.

Keywords: Alkaline phosphatase (ALP); Biomarkers; Metastatic castration-resistant prostate cancer (mCRPC); Outcomes; Prostate cancer; Prostate-specific antigen (PSA); Radium-223 (Ra-223); Survival risk.