Review on the Increasing Role for PSMA-Based Radioligand Therapy in Prostate Cancer.

Simple Summary: In 2021, the randomized controlled trial VISION showed that prostate-specific membrane antigen (PSMA)-based third-line radioligand therapy as monotherapy for patients with metastatic castration-resistant prostate cancer with positive lesions on PSMA PET/CT increases overall survival relative to the comparator treatment. The good results have inspired new trials. Our review provides a comprehensive update on post-VISION trials on RLT. The results are promising and may expand the role of PSMA-based RLT in patients with prostate cancer. In 2021, two randomized controlled trials (RCTs), TheraP and VISION, demonstrated that 177Lu-PSMA-617 as monotherapy was more effective for the decline of PSA than the comparator third-line treatments. Methods: Our review summarizes new RCTs that add to the use of radioligand therapy (RLT) for patients with high-risk prostate cancer (PCa). Results: Four past and present RCTs included 1081 patients. An RCT, ENZA-p, studied first-line treatment of patients with metastatic castration-resistant PCa (mCRPC). A combination of enzalutamide (ENZA) and 177Lu-PSMA-617 gave longer progression-free survival than ENZA as monotherapy. Other RCTs of patients with mCRPC, including the PSMAfore, and SPLASH trials, showed 177Lu-PSMA-617 as second-line treatment gave better progression-free survival than androgen receptor pathway inhibitors (combined p value < 6.9 × 10−6). Conclusions: Patients with PCa gain if they are given PSMA-RLT early in the treatment of PCa and as part of combination therapies. [ABSTRACT FROM AUTHOR]