Combination Radiopharmaceutical Approaches in Metastatic Castration-Resistant Prostate Cancer

Dr. Pedro Barata and Dr. Johann De Bono discuss emerging combination strategies involving radiopharmaceuticals in metastatic castration-resistant prostate cancer (mCRPC), with a focus on the scientific rationale behind combining these agents with other systemic therapies. Dr. De Bono reviews ongoing investigations evaluating radiopharmaceuticals alongside androgen receptor pathway inhibitors, PARP inhibitors, chemotherapy, and immunotherapy, highlighting how these approaches may enhance PSMA expression, increase DNA damage, and potentially improve tumor targeting. The discussion also explores evolving concepts surrounding alpha-emitting therapies, including radium Ra 223 dichloride and actinium-based approaches, as well as the growing interest in tandem and PSMA-targeted strategies. Importantly, the faculty emphasize the need to balance efficacy with tolerability, particularly regarding hematologic toxicities, chronic anemia, and long-term bone marrow effects associated with combination approaches. Together, the conversation provides insight into the future direction of radiopharmaceutical development and combination strategies in mCRPC.