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

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; Shozo, Okamoto; Emmett, Louise; Zacho, Helle D.; Ilhan, Harun; Rischpler, Christoph; Wetter, Axel; Schoder, Heiko; Burger, Irene A.; Slavik, Roger; Carroll, Peter R.; Lawhn-Heath, Courtney; Herrmann, Ken; Czernin, Johannes; Hope, Thomas A.

doi:10.1007/s00259-020-04945-1

Cited by 56Prostate Cancer Diagnosis and TreatmentRadiopharmaceutical Chemistry and ApplicationsMedical Imaging Techniques and Applications

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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

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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, Shozo, Okamoto, Emmett, Louise, Zacho, Helle D., Ilhan, Harun, Rischpler, Christoph, Wetter, Axel, Schoder, Heiko, Burger, Irene A., Slavik, Roger, Carroll, Peter R., Lawhn-Heath, Courtney, Herrmann, Ken, Czernin, Johannes, Hope, Thomas A.·2021·European Journal of Nuclear Medicine and Molecular Imaging

DOI 10.1007/s00259-020-04945-1PMC PMC7835157

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Abstract

Purpose: Readers need to be informed about potential pitfalls of [ 68 Ga]Ga-PSMA-11 PET interpretation. Methods: Here we report [ 68 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: [ 68 Ga]Ga-PSMA-11 PET at biochemical recurrence resulted in less than 10% false positive interpretations. Post-radiotherapy prostate uptake was a major source of [ 68 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.

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Sources of false positive or negative findings still remain with higher-specificity tracers and must be considered during image interpretation.
“However, sources of false positive or negative findings still remain with these tracers [131,132,133,134] and must be considered during image interpretation.”
From Influences on PET Quantification and Interpretation (2022) · cites this paper as [131]

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Authors: Fendler, W. P., Calais, J., Eiber, M., Simko, J. P., Kurhanewicz, J., Santos, R. D., Feng, F. Y., Reiter, R. E., Rettig, M. B., Nickols, N. G., Kishan, A. U., PSMA PET Reader Group, Shozo, O., Emmett, L., Zacho, H. D., Ilhan, H., Rischpler, C., Wetter, A., Schoder, H., Burger, I. A., Slavik, R., Carroll, P. R., Lawhn-Heath, C., Herrmann, K., Czernin, J., & Hope, T. A.
Affiliations: University of California, Los Angeles (US)
University of California, San Francisco (US)
Aalborg University Hospital (DK)
Ludwig-Maximilians-Universität München (DE)
Essen University Hospital (DE)
University of Duisburg-Essen (DE)
Corresponding author: Fendler, Wolfgang P.
ORCID: Fendler, Wolfgang P.
Eiber, Matthias
Kurhanewicz, John
Feng, Felix Y.
Reiter, Robert E.
Rettig, Matthew B.
Nickols, Nicholas G.
Kishan, Amar U.
Emmett, Louise
Zacho, Helle D.
Ilhan, Harun
Rischpler, Christoph
Burger, Irene A.
Carroll, Peter R.
Lawhn-Heath, Courtney
Herrmann, Ken
Hope, Thomas A.
Venue: European Journal of Nuclear Medicine and Molecular Imaging
Publisher: Springer Science and Business Media LLC
Published: 2020-08-17
Volume: 48
Issue: 2
Pages: 501-508
ISSN: 1619-7070 (ISSN-L)
1619-7089
DOI: 10.1007/s00259-020-04945-1
PMC: PMC7835157
OpenAlex: W3050429624
Cited by: 56
References: 22
Citations by year: 2026: 8 · 2025: 9 · 2024: 9 · 2023: 5 · 2022: 15 · 2021: 9 · 2020: 1
FWCI: 4.23
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0 (tdm)
creativecommons.org/licenses/by/4.0 (vor)
Locations: European Journal of Nuclear Medicine and Molecular Imaging (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
Zurich Open Repository and Archive (University of Zurich) (acceptedVersion, cc-by)
eScholarship (California Digital Library) (submittedVersion, cc-by)
Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion, cc-by)
Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion, other-oa)
VBN Forskningsportal (Aalborg Universitet) (submittedVersion, cc-by)
Zurich Open Repository and Archive (University of Zurich) (submittedVersion, cc-by)
Zurich Open Repository and Archive (University of Zurich)
Funders: Universitätsklinikum Essen
Topics: Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords: false positives, biochemically recurrent prostate cancer, pelvic lymph node metastasis
MeSH terms: Positron Emission Tomography Computed Tomography, Edetic Acid, Humans, Male, Neoplasm Recurrence, Local, Prospective Studies, Prostate, Prostatectomy, Prostatic Neoplasms

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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

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