The integration of [177Lu]Lu-prostate-specific membrane antigen (PSMA) therapy into the treatment paradigm for advanced prostate cancer has improved survival and quality of life; however, resistance and disease progression remain inevitable. Radionuclide combination strategies, particularly α-/β-emitter pairings, aim to overcome biological and dosimetric limitations of [177Lu]Lu-PSMA monotherapy. The AlphaBet trial demonstrated the feasibility and safety of combining the bone-seeking α-emitter radium-223 with [177Lu]Lu-PSMA in metastatic castration-resistant prostate cancer, underpinned by complementary spatial targeting and radiophysical properties. Ongoing studies are evaluating other novel combinations to overcome resistance, earlier integration to define optimal sequencing, and biomarker-driven approaches to refine patient selection. For patients, these strategies may enable more effective and durable treatments by combining different types of targeted radiation or systemic therapies; however, further studies are needed to confirm long-term benefits and safety.
European urology focus. 2026 May 30 [Epub ahead of print]
Louise Kostos, James P Buteau, Arun A Azad, Michael S Hofman
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia. Electronic address: ., Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia; Prostate Cancer Theranostics and Imaging Centre of Excellence (ProsTIC), Molecular Imaging and Therapeutic Nuclear Medicine, Cancer Imaging, Peter MacCallum Centre, Melbourne, Australia., Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, Australia.