How to cite: Yu, Evan Y. “Clinical Use of Lutetium-177–PSMA-617 for Metastatic Castrate Resistant Prostate Cancer.” November 25, 2025. Accessed Mar 2026. https://grandroundsinurology.com/clinical-use-of-lutetium-177-psma-617-for-metastatic-castrate-resistant-prostate-cancer/
In this presentation, urological specialists Dr. Evan Y. Yu, Dr. Daniel W. Lin, and Dr. Amir Iravani from the University of Washington in Seattle, Washington, discuss the practical clinical use of Lutetium-177–PSMA-617 for metastatic prostate cancer, including patient selection using prostate-specific membrane antigen (PSMA) positron emission tomography (PET), workflow considerations, safety monitoring, and strategies for preventing adverse events. The experts also review emerging clinical trial data that may shape future sequencing of radioligand therapy.
Evan Y. Yu, MD, Medical Oncologist, presents the therapeutic framework for Lutetium-177–PSMA-617 in metastatic prostate cancer. Dr. Yu explains that Lutetium-177–PSMA-617, a radioligand composed of a PSMA-targeting molecule linked to Lutetium-177, delivers beta radiation to PSMA-expressing cancer cells. Amir Iravani, MD, Nuclear Medicine Physician, states that this therapeutic approach builds upon diagnostic PSMA PET, which has already demonstrated high sensitivity in detecting metastatic disease.
Daniel W. Lin, MD, Chief of Urological Oncology, describes the expanding use of PSMA PET in the initial staging of unfavorable intermediate and high-risk prostate cancer, in biochemical recurrence after local therapy, and in metastatic castration resistant disease. He notes that the modality detects nodal and osseous metastases at low prostate-specific antigen (PSA) levels and increasingly guides treatment decisions throughout the disease course.
Dr. Yu explains that Lutetium-177–PSMA-617 first gained approval for metastatic castration resistant prostate cancer after an androgen receptor pathway inhibitor (ARPI) and docetaxel, and later received approval in the pre-chemotherapy setting. Dr. Iravani reports growing referral volume for pre-chemotherapy patients who prefer radioligand therapy because of concerns related to cytotoxic chemotherapy toxicity profiles.
The panel addresses patient selection criteria for Lutetium-177–PSMA-617. Suitable candidates typically show PSMA uptake greater than liver background and lack PSMA-negative visceral lesions, particularly in the liver. Uniformly, PSMA-avid polymetastatic disease suggests a higher likelihood of response. Routine monitoring includes laboratory evaluation for cytopenias, xerostomia, and renal parameters during six-week dosing intervals.
The group also discusses early PSMA addition study results in metastatic hormone-sensitive disease, which show an improvement in radiographic progression-free survival with the addition of Lutetium-177–PSMA-617 to androgen deprivation therapy (ADT) and an ARPI. Interpretation of overall survival outcomes remains limited due to early follow-up and high crossover rates.
