PSMA Radiotheranostics in Prostate Cancer: Principles, Practice, and Future Prospects.

Prostate cancer is a leading cause of cancer-related mortality in men, with metastatic castration-resistant prostate cancer presenting a substantial treatment challenge. The authors focuse on prostate-specific membrane antigen (PSMA) radiotheranostics, particularly lutetium 177 (Lu)-PSMA radioligand therapy, as an emerging treatment modality for metastatic castration-resistant prostate cancer. The U.S. Food and Drug Administration approval of Lu-PSMA-617 marked a substantial advancement in the treatment paradigm of metastatic castration-resistant prostate cancer, based on the VISION trial that showed improved overall survival and quality of life compared with those for standard care. PSMA expression, assessed via PSMA PET, is crucial for patient selection and assessment of treatment eligibility. The authors discuss current practices, including therapy administration, dosing, and side effects, with a particular focus on eligibility criteria and the added value of posttherapy imaging. Response assessment criteria using PSMA PET are discussed, although these require further validation. The discussion of future directions highlights ongoing trials investigating PSMA targeting agents, the extension of radioligand therapy to earlier stages of prostate cancer, and combination therapies. This review underscores the role of PSMA radioligand therapy in the evolving landscape of prostate cancer treatment and its promise for improving patient outcomes. RSNA, 2024 Supplemental material is available for this article.