Optimal Imaging Strategies After Negative PSMA PET/CT Results in Patients With Prostate Cancer Biochemical Recurrence: AJR Expert Panel Narrative Review.

PSMA PET/CT has become widely incorporated into restaging algorithms for patients with biochemical recurrence (BCR) of prostate cancer, defined as a rising PSA level after attempted curative therapy. A substantial proportion of patients with BCR demonstrate no detectable disease on PSMA PET/CT. In these patients, management remains challenging as clinicians must balance risks of undertreatment of occult disease and potential morbidity of empiric salvage therapies with a potential missed therapeutic window from further diagnostic workup. Guidelines recommend not withholding salvage radiation therapy based on negative PSMA PET/CT results. In practice, additional imaging is frequently pursued to attempt to localize disease before salvage treatment. This AJR Expert Panel Narrative Review examines the available evidence addressing the ongoing uncertainty surrounding optimal imaging strategies and related management after a negative PSMA PET/CT examination in patients with BCR. We review performance characteristics of initial and repeat PSMA PET/CT examinations, explore prognostic factors that may guide imaging timing and selection, and evaluate the role of radiotracers other than PSMA and modalities other than PET. Based on the presented information, we provide consensus statements for imaging strategies emphasizing PSA kinetics and tumor biology while acknowledging areas where additional data are needed for informed clinical decision-making.