How to cite: Morris MJ, Calais J, and Shore ND. “Sequencing Lu-177 PSMA-directed RLT.” August 15, 2025. Accessed Feb 2026. https://grandroundsinurology.com/sequencing-lu-177-psma-directed-rlt/
Summary
This expert panel discussion features Michael J. Morris, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, New York, New York; Jérémie Calais, MD, PhD, Nuclear Medicine Physician, University of California, Los Angeles, Los Angeles, California; and Neal D. Shore, MD, Urologist, Atlantic Urology Specialists, Myrtle Beach, South Carolina. The experts explore how emerging clinical evidence is reshaping the sequencing of Lu-177 prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) across the prostate cancer spectrum. Dr. Morris reviews the foundational VISION trial, which established Lu-177–PSMA-617 as an effective life-prolonging therapy in late-stage metastatic castration-resistant prostate cancer (mCRPC). He highlights VISION’s significant improvements in radiographic progression-free survival and overall survival, along with its relatively low screen-failure rate due to permissive imaging criteria.
The discussion then transitions to earlier-line integration of RLT. Dr. Calais reviews the PSMAfore study, which evaluates Lu-177–PSMA-617 in androgen receptor pathway inhibitor (ARPI)-pretreated but taxane-naïve mCRPC. The panel highlights PSMAfore’s positive radiographic progression-free survival (PFS) results and patient-reported outcomes, while acknowledging that the crossover allowance complicates the interpretation of overall survival (OS). Dr. Shore emphasizes how these results may influence sequencing decisions in patients who progress on first-line androgen receptor pathway inhibitors (ARPIs) yet are not ideal chemotherapy candidates.
The panel examines the PSMA Addition trial, which tests the incorporation of Lu-177 earlier in the disease course, within metastatic hormone-sensitive prostate cancer (mHSPC) alongside androgen deprivation therapy (ADT) and ARPI. Although OS data remain immature, notable improvements in radiographic PFS hint at further upstream movement of radioligand therapy. The speakers discuss how disease volume, systemic therapy backbones, and evolving biomarker insights, including imaging intensity and heterogeneity, may eventually guide differential treatment pathways.
The experts stress the importance of understanding inclusion criteria, managing expectations around OS endpoints, and anticipating future combinations and sequencing strategies. Together, the data paint a rapidly evolving landscape in which Lu-177–PSMA therapy is steadily moving earlier in the disease continuum, raising practical questions for clinicians regarding timing, patient selection, and imaging-based decision making.
