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.
AJR. American journal of roentgenology. 2026 Jul 15 [Epub ahead of print]
Wonkyu P Choi, Frankis G Almaguel, Elisa Franquet-Elia, Sangeet Ghai, Michael A Gorin, Michael Repka, Rodney J Hicks, Baris Turkbey, Lale Umutlu, Steven P Rowe, Spencer C Behr
The Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, USA., Molecular Imaging and Therapeutics, Loma Linda University Cancer Center, Loma Linda, CA, USA., Department of Radiology, University of Massachusetts Chan Medical School, Worcester, MA, USA., Joint Department of Medical Imaging, University Medical Imaging Toronto, University of Toronto, Toronto, Canada., Milton and Carroll Petrie Department of Urology, Icahn School of Medicine at Mount Sinai, New York, NY, USA., Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA., The University of Melbourne Department of Medicine, St Vincent's Hospital, Melbourne, Australia., Molecular Imaging Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA., Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Germany., Department of R adiology, University of Texas Southwestern Medical Center, Dallas, TX, USA., Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, USA.