Prostate-specific membrane antigen radioligand therapy (PSMA-RLT) is approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Following the phase 3 VISION clinical trial showing prolonged overall and progression-free survival after PSMA-RLT, 177Lu-PSMA-617 was initially introduced as a standard of care for patients with mCRPC with prior exposure to an androgen receptor pathway inhibitor (ARPI) and taxane chemotherapy. In recent years, three phase 3 clinical trials with published, presented, or announced results (PSMAfore, SPLASH, and ECLIPSE, respectively) have shown that PSMA-RLT delays progression-free survival when compared with a change in ARPI in patients with post-ARPI, chemotherapy-naive mCRPC. This mini-review summarizes the available results from these phase 3 trials and select randomized phase 2 trials and discusses their impact on mCRPC management and optimal sequencing of PSMA-RLT. PATIENT SUMMARY: PSMA-RLT is a targeted radioactive drug that prolongs the lives of patients living with advanced prostate cancer when given after chemotherapy. PSMA-RLT has also been shown to delay cancer progression in patients who have not received any chemotherapy, making it an emerging option for those who are not eligible for chemotherapy.
European urology focus. 2026 Jun 23 [Epub ahead of print]
Jean-Mathieu Beauregard, Michael Ong, Frédéric Pouliot
Department of Radiology and Nuclear Medicine, Université Laval, Quebec City, Canada; Division of Nuclear Medicine, Department of Medical Imaging, CHU de Québec - Université Laval, Quebec City, Canada. Electronic address: ., Division of Medical Oncology, Department of Medicine, Ottawa Hospital Research Institute, Ottawa, Canada., Department of Surgery, Université Laval, Quebec City, Canada; Division of Urology, Department of Surgery, CHU de Québec - Université Laval, Quebec City, Canada.