PSMA PET-directed radiotherapy for prostate cancer: From precision planning to future innovations

Positron emission tomography (PET), particularly with prostate-specific membrane antigen (PSMA) tracers, has revolutionized the clinical management of prostate cancer (PCa). This review highlights the pivotal role of PET molecular imaging in guiding radiotherapy (RT) across diverse clinical scenarios, from postoperative biochemical recurrence to oligometastatic disease. Growing evidence shows that PET excels in lesion detection, enhances target volume delineation, enables focal dose escalation, and guides treatment intensification. PSMA PET increases the precision of RT planning, supports personalized therapeutic approaches, and is associated with improved outcomes, including biochemical recurrence-free and metastasis-free survival. The integration of PET with advanced RT technologies, including biology-guided radiotherapy (BgRT), is paving the way for real-time, biologically adaptive treatment paradigms. However, challenges remain, including the need for standardized protocols, management of tracer variability, and clinical translation of innovations such as PET-linear accelerator (LINAC) into routine practice. Future research should prioritize large-scale, prospective studies to establish the clinical efficacy, cost-effectiveness, and optimal integration of PET-guided RT in PCa care.