3287 - Investigation of the Safety of Radium-223 Chloride in Combination with External Beam Radiotherapy for Bone Metastases of Prostate Cancer

Purpose/Objective(s): Radium-223 chloride (Ra-223) has demonstrated efficacy in relieving pain and improving survival in patients with castration-resistant prostate cancer (CRPC) and bone metastases, as shown in the ALSYMPCA trial. However, uncertainties remain regarding the optimal timing of Ra-223 therapy and its safety when combined with external beam radiation therapy (EBRT). This study aimed to investigate the safety of combining Ra-223 therapy with EBRT for patients with CRPC and multiple bone metastases, including lesions requiring urgent treatment, such as those causing neurological symptoms due to spinal cord compression. We hypothesized that concurrent Ra-223 and EBRT would not increase adverse events compared to Ra-223 alone.

Materials/Methods: This retrospective study analyzed data from patients with CRPC and bone metastases treated with Ra-223 therapy at our institution between September 2018 and December 2023. Concurrent EBRT was defined as EBRT delivered to a bone lesion within 4 weeks of initiating Ra-223 therapy. The primary endpoint was the incidence of grade 2 or higher adverse events. Secondary endpoints included treatment completion rate, survival, and symptom palliation. Adverse events were evaluated using CTCAE version 4.0. Survival rates were calculated using the Kaplan–Meier method, and significance tests were performed using the log-rank method.

Results: Of the 23 patients referred for Ra-223 therapy, 17 were included in this analysis as they had completed or discontinued treatment. Concurrent EBRT was administered in 8 patients for symptomatic lesions, including spinal cord compression. Nine patients received Ra-223 alone. The median follow-up period was 20 months. The overall treatment completion rate was 52.9% (50.0% in the concurrent EBRT group and 55.6% in the Ra-223 alone group). Grade 2 or higher adverse events occurred in 7 patients (41.2%), and grade 3 or higher in 2 (11.7%). The most common adverse event was anemia. One patient experienced grade 5 Pneumocystis jirovecii pneumonia, possibly due to steroid use for neurological symptoms and the patient’s underlying diabetes mellitus. No gastrointestinal toxicity was observed in patients receiving EBRT encompassing the intestinal tract. The 2-year overall survival rate was 56.9%. Super bone scan on pretreatment bone scintigraphy was a significant poor prognostic factor for survival (p=0.010). Limitations include the small sample size, retrospective design, and lack of Bone Scan Index data.

Conclusion: Combining Ra-223 with EBRT appears to be a potentially safe approach for managing patients with CRPC who experience symptomatic bone metastases requiring palliative radiotherapy. Careful patient selection, appropriate EBRT field design, and dose optimization are crucial. Attention should be paid to anemia, especially in patients with super bone scans. Further prospective studies are needed to confirm these findings and evaluate long-term safety and efficacy.