Related Experiment Video
Updated: Dec 11, 2025
A Cognitive Fusion-guided Prostate Biopsy Using Multiparametric Magnetic Resonance Imaging and Transrectal Ultrasound
Published on: March 21, 2025
False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a
Wolfgang P Fendler1,2, Jeremie Calais3, Matthias Eiber3,4
1Department of Molecular and Medical Pharmacology, Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA. wolfgang.fendler@uk-essen.de.
Purpose:
Readers need to be informed about potential pitfalls of [68Ga]Ga-PSMA-11 PET interpretation.
Methods:
Here we report [68Ga]Ga-PSMA-11 PET findings discordant with the histopathology/composite reference standard in a recently published prospective trial on 635 patients with biochemically recurrent prostate cancer.
Results:
Consensus reads were false positive in 20 regions of 17/217 (8%) patients with lesion validation. Majority of the false positive interpretations (13 of 20, 65%) occurred in the context of suspected prostate (bed) relapse (T) after radiotherapy (n = 11); other false positive findings were noted for prostate bed post prostatectomy (T, n = 2), pelvic nodes (N, n = 2), or extra pelvic lesions (M, n = 5). Major sources of false positive findings were PSMA-expressing residual adenocarcinoma with marked post-radiotherapy treatment effect. False negative interpretation occurred in 8 regions of 6/79 (8%) patients with histopathology validation, including prostate (bed) (n = 5), pelvic nodes (n = 1), and extra pelvic lesions (n = 2). Lesions were missed mostly due to small metastases or adjacent bladder/urine uptake.
Conclusion:
[68Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [68Ga]Ga-PSMA-11 PET false positivity. In few cases, PET correctly detects residual PSMA expression post-radiotherapy, originating however from treated, benign tissue or potentially indolent tumor remnants.
Trial Registration Number:
ClinicalTrials.gov Identifiers: NCT02940262 and NCT03353740.
