Bone-Targeting Radionuclides in the Treatment of Metastatic Castration-Resistant Prostate Cancer: A Review on Radium-223 Chloride (Alpharadin) in Combination with Other Therapies

Abstract

Recent advances have broadened the range of therapeutic options for mCRPC, with several new treatments, including novel hormonal therapies (enzalutamide, abiraterone), chemotherapeutic agents (docetaxel, cabazitaxel), immunotherapies (sipuleucel-T), and bone targeting radiopharmaceuticals (radium-223) showing improved clinical outcomes and receiving U.S. Food and Drug Administration approval. These new treatments provide new avenues for improving patient survival and quality of life. Radium-223, a targeted alpha-emitter, specifically targets bone metastases, offering palliative benefits and a potential increase in life expectancy. The integration of radium-223 with other treatments shows promise for managing mCRPC. However, the optimal sequencing and combination of radium-223 with other therapies are still being explored, with various clinical trials investigating new therapeutic approaches. The integration of these therapies, especially to provide more effective, personalized treatment strategies, requires further investigation. A thorough literature review was conducted on current treatments for mCRPC, including chemotherapeutic agents, oral hormonal therapies targeting the androgen receptor axis, immunotherapies, and radium-223. Ongoing clinical trials investigating radium-233 in the context of other therapies for the treatment of mCRPC patients were also reviewed. Further studies should focus on determining the optimal sequencing and dosing and identifying biomarkers that predict treatment response to enhance outcomes of mCRPC patients. This review underlines the rational strategies of combining radium-223 with other therapies, investigating their impact on bone in terms of delaying skeletal-related events, and managing bone disease progression in mCRPC patients.