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

ImportanceIn retrospective studies, Ga-68-PSMA-11 positron emission tomographic (PET) imaging improves detection of biochemically recurrent prostate cancer compared with conventional imaging. ObjectiveTo assess Ga-68-PSMA-11 PET accuracy in a prospective multicenter trial. Design, Setting, and ParticipantsIn 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 Ga-68-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 MeasuresEndpoints were positive predictive value (PPV), detection rate, interreader reproducibility, and safety. ResultsA 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). Ga-68-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 kappa, 0.65-0.78). There were no serious adverse events associated with Ga-68-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 RelevanceUsing blinded reads and independent lesion validation, we establish high PPV for Ga-68-PSMA-11 PET, detection rate and interreader agreement for localization of recurrent prostate cancer. Trial RegistrationClinicalTrials.gov identifiers: NCT02940262 and NCT03353740