PSMA PET Imaging in the Postradiotherapy Setting: Implications for the Diagnosis of Recurrent Prostate Cancer

Prostate-specific membrane antigen (PSMA) PET/CT is a highly sensitive tool for detecting metastatic prostate cancer. While its role in staging and advanced disease is well established, its diagnostic role after local therapies-particularly radiotherapy (RT)-remains less defined. This review analyzes the use of PSMA PET/CT after RT in hormone-sensitive and oligometastatic patients treated with metastasis-directed radiotherapy (MDRT). A key challenge is the interpretation of uptake in irradiated regions-such as the prostate bed, lymph nodes, and bone-where inflammation or fibrosis may cause false positives. We also address the modulation of PSMA expression by RT and by androgen receptor inhibitors. Both can induce transient increases in tracer uptake (flare phenomenon) without true progression. The timing and clinical meaning of this effect remain uncertain in hormone-naïve disease. Finally, we review quantitative PET biomarkers such as SUVmax, SUVmean, PSMA-TV, PSMA-TL, and tumor asphericity (ASP). These metrics show prognostic potential but lack validated criteria in the post-RT setting. In summary, current evidence highlights the need to clarify the role of PSMA PET/CT after RT. A better definition of its diagnostic value is essential to guide treatment decisions and future clinical guideline.