Wolfgang P Fendler1,2, Jeremie Calais3, Matthias Eiber3,4, Jeffrey P Simko5, John Kurhanewicz6, Romelyn Delos Santos6, Felix Y Feng6, Robert E Reiter7, Matthew B Rettig7,8, Nicholas G Nickols7,9, Amar U Kishan10, Roger Slavik3, Peter R Carroll6, Courtney Lawhn-Heath11, Ken Herrmann3,12, Johannes Czernin3, Thomas A Hope11. 1. Department of Molecular and Medical Pharmacology, Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA. wolfgang.fendler@uk-essen.de. 2. Department of Nuclear Medicine, University of Duisburg-Essen, Essen, Germany. wolfgang.fendler@uk-essen.de. 3. Department of Molecular and Medical Pharmacology, Ahmanson Translational Imaging Division, University of California Los Angeles, Los Angeles, CA, USA. 4. Department of Nuclear Medicine, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany. 5. Department of Anatomic Pathology and Department of Urology, University of California San Francisco, San Francisco, CA, USA. 6. Department of Urology, University of California San Francisco, San Francisco, CA, USA. 7. Department of Urology, UCLA Medical Center, University of California Los Angeles, Los Angeles, CA, USA. 8. Department of Medicine, Division of Hematology/Oncology, University of California Los Angeles, Los Angeles, CA, USA. 9. Department of Radiation Oncology, VA Greater Los Angeles Healthcare System, University of California Los Angeles, Los Angeles, CA, USA. 10. Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA. 11. Departments of Radiology and Biomedical Imaging and Pharmaceutical Chemistry, University of California San Francisco, San Francisco, CA, USA. 12. Department of Nuclear Medicine, University of Duisburg-Essen, Essen, Germany.
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.
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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