Retreatment of Metastatic Castration-Resistant Prostate Cancer Patients with²²³Ra Therapy in Daily Practice

²²³Ra-dichloride (²²³Ra) is an approved therapeutic option for patients with metastatic castration-resistant prostate cancer (mCRPC) who have symptomatic bone metastases. After an initial course of 6 ²²³Ra injections, treatment may be repeated. The purpose of this study was to evaluate the safety and efficacy of ²²³Ra retreatment of mCRPC in a real-world population. <b>Methods:</b> This multicenter, retrospective cohort study included patients who had mCRPC and bone metastases who previously received 6 consecutive injections of ²²³Ra and received at least 1 ²²³Ra retreatment injection between 2014 and 2024. The primary endpoint was safety, measured as hematologic and nonhematologic adverse events (AEs), including skeletal-related events. Secondary endpoints included the number of injections administered, overall survival, and biochemical response rates. Exploratory analyses intended to identify variables associated with alkaline phosphatase response during retreatment, completion of ²²³Ra retreatment, and overall survival. <b>Results:</b> Sixty-one patients were evaluated. Median age was 75 y, 44% of patients received prior chemotherapy, and 87% of patients previously received at least 1 androgen receptor pathway inhibitor. The median number of prior systemic therapies was 3. In total, 56 patients (95%) experienced at least 1 hematologic AE, including 14% with grade 3 hematologic AEs. Forty-four patients (72%) experienced at least 1 nonhematologic AE during ²²³Ra retreatment. No grade 4 or 5 AEs occurred. Patients received a median of 6 ²²³Ra retreatment injections. Overall survival was 16.9 mo (95% CI, 11.9-21.9 mo), and 56% of patients had an alkaline phosphatase response of at least 30%. High baseline hemoglobin levels, no prior chemotherapy, and a prostate-specific antigen response of at least 30% during the initial ²²³Ra course were predictors for completion of 6 ²²³Ra retreatment injections. A prior skeletal-related event, baseline performance status, and baseline hemoglobin level were prognostic for survival in this population. <b>Conclusion:</b> ²²³Ra retreatment was well tolerated and is therefore deemed safe in selected patients with mCRPC. In addition, the high number of administered injections and the high alkaline phosphatase response rate suggest that retreatment is beneficial to patients with advanced mCRPC. Patients with high hemoglobin levels, good performance status, and prior prostate-specific antigen response to ²²³Ra therapy may be the best candidates for ²²³Ra retreatment.