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

  • Author(s): Fendler, Wolfgang P;
  • Calais, Jeremie;
  • Eiber, Matthias;
  • Simko, Jeffrey P;
  • Kurhanewicz, John;
  • Santos, Romelyn Delos;
  • Feng, Felix Y;
  • Reiter, Robert E;
  • Rettig, Matthew B;
  • Nickols, Nicholas G;
  • Kishan, Amar U;
  • PSMA PET Reader Group;
  • Slavik, Roger;
  • Carroll, Peter R;
  • Lawhn-Heath, Courtney;
  • Herrmann, Ken;
  • Czernin, Johannes;
  • Hope, Thomas A
  • et al.
Abstract

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.

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