False positive PSMA PET for tumor remnants in the irradiated prostate and other interpretation pitfalls in a prospective multi-center trial
Wolfgang P. Fendler, Jérémie Calais, Matthias Eiber, Jeffrey P. Simko, John Kurhanewicz, Romelyn Delos Santos, Felix Y. Feng, Robert E. Reiter, Matthew B. Rettig, Nicholas G. Nickols, Amar U. Kishan, PSMA PET Reader Group, Shozo Okamoto, Louise Emmett, Helle D. Zacho, Harun Ilhan, Christoph Rischpler, Axel Wetter, Heiko Schöder, Irene A. Burger, Roger Slavik, Peter R. Carroll, Courtney Lawhn-Heath, Ken Herrmann, Johannes Czernin, Thomas A. Hope
Abstract
PURPOSE: Ga]Ga-PSMA-11 PET interpretation. METHODS: Ga]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: Ga]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.