Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial

Wolfgang P Fendler, Jeremie Calais, Matthias Eiber, Robert R Flavell, Ashley Mishoe, Felix Y Feng, Hao G Nguyen, Robert E Reiter, Matthew B Rettig, Shozo Okamoto, Louise Emmett, Helle D Zacho, Harun Ilhan, Axel Wetter, Christoph Rischpler, Heiko Schoder, Irene A Burger, Jeannine Gartmann, Raven Smith, Eric J SmallRoger Slavik, Peter R Carroll, Ken Herrmann, Johannes Czernin, Thomas A Hope

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Abstract

Importance: In retrospective studies, 68Ga-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. Objective: To assess 68Ga-PSMA-11 PET accuracy in a prospective multicenter trial. Design, Setting, and Participants: In this single-arm prospective trial conducted at University of California, San Francisco and University of California, Los Angeles, 635 patients with biochemically recurrent prostate cancer after prostatectomy (n = 262, 41%), radiation therapy (n = 169, 27%), or both (n = 204, 32%) underwent 68Ga-PSMA-11 PET. Presence of prostate cancer was recorded by 3 blinded readers on a per-patient and per-region base. Lesions were validated by histopathologic analysis and a composite reference standard. Main Outcomes and Measures: Endpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. Results: A total of 635 men were enrolled with a median age of 69 years (range, 44-95 years). On a per-patient basis, PPV was 0.84 (95% CI, 0.75-0.90) by histopathologic validation (primary endpoint, n = 87) and 0.92 (95% CI, 0.88-0.95) by the composite reference standard (n = 217). 68Ga-PSMA-11 PET localized recurrent prostate cancer in 475 of 635 (75%) patients; detection rates significantly increased with prostate-specific antigen (PSA): 38% for <0.5 ng/mL (n = 136), 57% for 0.5 to <1.0 ng/mL (n = 79), 84% for 1.0 to <2.0 ng/mL (n = 89), 86% for 2.0 to <5.0 ng/mL (n = 158), and 97% for ≥5.0 ng/mL (n = 173, P <.001). Interreader reproducibility was substantial (Fleiss κ, 0.65-0.78). There were no serious adverse events associated with 68Ga-PSMA-11 administration. PET-directed focal therapy alone led to a PSA drop of 50% or more in 31 of 39 (80%) patients. Conclusions and Relevance: Using blinded reads and independent lesion validation, we establish high PPV for 68Ga-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. Trial Registration: ClinicalTrials.gov identifiers: NCT02940262 and NCT03353740.

Original languageEnglish
JournalJAMA Oncology
Volume5
Issue number6
Pages (from-to)856-863
Number of pages8
ISSN2374-2437
DOIs
Publication statusPublished - 1 Jun 2019

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Fendler, W. P., Calais, J., Eiber, M., Flavell, R. R., Mishoe, A., Feng, F. Y., Nguyen, H. G., Reiter, R. E., Rettig, M. B., Okamoto, S., Emmett, L., Zacho, H. D., Ilhan, H., Wetter, A., Rischpler, C., Schoder, H., Burger, I. A., Gartmann, J., Smith, R., ... Hope, T. A. (2019). Assessment of 68Ga-PSMA-11 PET Accuracy in Localizing Recurrent Prostate Cancer: A Prospective Single-Arm Clinical Trial. JAMA Oncology, 5(6), 856-863. https://doi.org/10.1001/jamaoncol.2019.0096