How will PLUDO, PSMAfore, SPLASH, and ECLIPSE Impact Prostate Cancer Management?

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.