PSMA-PET Guided Radiotherapy in Prostate Cancer: A Critical Review of Current Applications and Future Directions

Prostate-specific membrane antigen/positron emission tomography (PSMA-PET) changed the diagnostic approach in prostate cancer (PCa), providing superior diagnostic accuracy compared to conventional imaging (CI) modalities like computed tomography (CT), bone scintigraphy (BS) or other PET radiopharmaceuticals like choline or fluciclovine. This improved diagnostic accuracy plays a crucial role in its synergy with radiotherapy, particularly in the context of metastasis-directed therapy. Even in advanced stages of prostate cancer, the synergy with radiotherapy is evident in the promising results emerging from the combination of RT and RLT. To evaluate the value of PSMA as biomarker, the technological advancements in PSMA-PET, and its integration into clinical practice, focusing on its impact on RT and RLT. A comprehensive nonsystematic literature review was performed using PubMed/MEDLINE and EMBASE biomedical databases. Literature search was updated until March 2025. The most relevant studies have been summarized, giving priority to registered clinical trials and multicenter collaborations. The higher accuracy of PSMA-PET is advancing RT planning in PCa, from initial staging to salvage and metastasis-directed therapy. Ongoing trials combining RLT with external beam radiotherapy (EBRT) may expand its role into earlier stages. Key challenges include the need for long-term outcome data, standardization, cost-effectiveness, and avoiding overtreatment. Future efforts should optimize PSMA-guided RT, evaluate novel RLT combinations, and identify predictive biomarkers for personalized care. The synergy between PSMA-PET and radiotherapy enables a more effective therapeutic approach across both early and advanced stages of PCa, particularly through the promising integration with RLT.