Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) is now an established treatment for metastatic castration-resistant prostate cancer (mCRPC), demonstrating improved oncologic outcomes and incorporation into international guidelines. Landmark trials including VISION, TheraP, and PSMAfore have defined the efficacy, safety, and clinical role of [177Lu] Lu-PSMA-617, showing improvements in survival, progression-free survival, and biochemical response rates. Appropriate patient selection remains critical, relying on PSMA positron emission tomography imaging, disease burden assessment, and multidisciplinary evaluation. Emerging imaging biomarkers may further refine selection but remain investigational. Beyond heavily pretreated mCRPC, evidence is expanding for earlier use in taxane-naïve disease, metastatic hormone-sensitive prostate cancer, and neoadjuvant settings. This Clinical Consultation Guide summarises contemporary evidence, practical treatment considerations, toxicity monitoring, and future directions for integrating PSMA-RLT into prostate cancer management.
European urology focus. 2026 Jun 28 [Epub ahead of print]
David Hennes, Abdullah Al-Khanaty, Mylestone Monna, Nathan Lawrentschuk, Marlon L Perera, Renu S Eapen, James P Buteau, Michael S Hofman, Declan G Murphy
Department of Urology, Austin Health, Melbourne, Australia; Monash University, Hudson Institute of Medical Research, Melbourne, Australia., Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Department of Surgery, Austin Health, Melbourne, Australia., Department of Urology, Austin Health, Melbourne, Australia., Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Department of Surgery, Royal Melbourne Hospital, Melbourne, Australia; EJ Whitten Prostate Cancer Research Centre at Epworth Healthcare, Melbourne, Australia., Department of Urology, Austin Health, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Department of Surgery, Austin Health, Melbourne, Australia., Department of Urology, Austin Health, Melbourne, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, Australia., Department of Molecular Imaging and Therpeautic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia; Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer, Melbourne, Australia., Department of Molecular Imaging and Therpeautic Nuclear Medicine, Peter MacCallum Cancer Centre, Melbourne, Australia; Prostate Cancer Theranostics and Imaging Centre of Excellence, Peter MacCallum Cancer, Melbourne, Australia; University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, Australia., Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Australia; University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, Australia. Electronic address: .