Novel radionuclide therapy combinations in prostate cancer

Prostate cancer remains the commonest cancer diagnosed in males and a leading cause of cancer-related death. Men with metastatic castration-resistant prostate cancer (mCRPC) who have progressed on chemotherapy and androgen receptor pathway inhibitors (ARPI) have limited treatment options, significant morbidity, and poor outcomes. Prostate-specific membrane antigen (PSMA)-directed radionuclide therapy (RNT) is emerging as an efficacious and well-tolerated therapy; however, disease progression is universal. Several ongoing RNT trials focus on combination strategies to improve efficacy and durability of treatment response, including combinations with ARPIs, chemotherapy, immunotherapy, and targeted therapies. Further, efforts are underway to expand the role of PSMA-directed RNT to earlier stages of disease including hormone-sensitive and localized prostate cancer. In this review, we discuss the rationale and ongoing RNT combination therapeutic trials in prostate cancer and summarize the efficacy and toxicity associated with RNT.