Simple SummaryRadium-223 is a bone-targeted radiopharmaceutical that has been shown to improve overall survival (OS) and reduce bone pain in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we evaluated the efficacy and safety of radium-223 in patients with mCRPC who had received prior treatment with enzalutamide or abiraterone. We found that patients who received enzalutamide prior to radium-223 had a significantly longer median OS (25.1 months vs. 14.8 months) than those who received abiraterone. We also found that patients who received more than five doses of radium-223 had a longer median OS than those who received fewer doses. These findings suggest that the use of enzalutamide prior to radium-223 and the number of doses of radium-223 received may impact OS in patients with mCRPC.AbstractMetastatic castration-resistant prostate cancer (mCRPC) is a progressive stage of prostate cancer that often spreads to the bone. Radium-223, a bone-targeting radiopharmaceutical, has been shown to improve the overall survival in mCRPC in patients without visceral metastasis. However, the impact of prior systemic therapy on the treatment outcome of mCRPC patients receiving radium-223 remains unclear. This study aimed to investigate the optimal choice of systemic therapy before radium-223 in mCRPC patients. The study included 41 mCRPC patients who received radium-223 therapy, with 22 receiving prior enzalutamide and 19 receiving prior abiraterone. The results showed that the median overall survival was significantly longer in the enzalutamide group than in the abiraterone group (25.1 months vs. 14.8 months,p= 0.049). Moreover, the number of patients requiring blood transfusion was higher in the abiraterone group than in the enzalutamide group (9.1% vs. 26.3%,p= 0.16). The study also found that the number of doses of Radium-223 received was significantly associated with overall survival (≥5 vs. <5, HR 0.028, 95%CI 0.003–0.231,p= 0.001). Our study provides insights into the optimal treatment choice for mCRPC prior to radium-223, indicating that enzalutamide prior to radium-223 administration may have better outcomes compared to abiraterone in mCRPC patients without visceral metastasis.