Combination prostate-specific membrane antigen-targeted radiopharmaceutical therapy in metastatic prostate cancer

Radiopharmaceutical therapy is emerging rapidly as an effective and safe pillar in cancer management. The regulatory approvals for ¹⁷⁷Lu-PSMA-617 radiopharmaceutical therapy in both the pre- and post-chemotherapy metastatic castration resistant prostate cancer clinical space have paved the way for the implementation of this life-prolonging therapy in clinical practice. However, the emergence of resistance to radiopharmaceutical therapy is inevitable, and therefore, combination therapies will be needed to synergize treatment efficacy without untoward collective toxicity. Biologically rational combination therapies across various phases of prostate cancer will lead to more optimal patient outcomes than what can be achieved with monotherapy. This article summarizes select clinical trials on prostate-specific membrane antigen-targeted radiopharmaceutical therapy in combination with other treatments that are either actively accruing or have provided preliminary results.