False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial

Eur J Nucl Med Mol Imaging. 2021 Feb;48(2):501-508. doi: 10.1007/s00259-020-04945-1. Epub 2020 Aug 17.


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.

Keywords: Interpretation; PET; PSMA; Pitfall; Radiotherapy; Recurrence.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Edetic Acid
  • Humans
  • Male
  • Neoplasm Recurrence, Local
  • Positron Emission Tomography Computed Tomography
  • Prospective Studies
  • Prostate*
  • Prostatectomy
  • Prostatic Neoplasms* / diagnostic imaging
  • Prostatic Neoplasms* / radiotherapy
  • Prostatic Neoplasms* / surgery


  • Edetic Acid

Associated data

  • ClinicalTrials.gov/NCT02940262
  • ClinicalTrials.gov/NCT03353740