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

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.

Conflict of interest statement

Conflict of Interest Disclosures: Wolfgang Fendler is a consultant for Endocyte and Ipsen and received personal fees from Radiomedix. Matthias Eiber received funding from Blue Earth Diagnostics and ABX as part of an academic collaboration. Harun Ilhan is an advisory board member for Bayer and received research funding from Novartis. Matthias Eiber is a consultant for ABX and Blue Earth Diagnostics. Heiko Schoder served as a consultant to Aileron Therapeutics until June 2018. Ken Herrmann reports personal fees from Bayer, other from Sofie Biosciences, personal fees from SIRTEX, other from ABX, personal fees from Adacap, personal fees from Curium, personal fees from Endocyte, grants and personal fees from BTG, personal fees from IPSEN, personal fees and nonfinancial support from Siemens Healthineers, and nonfinancial support from GE Healthcare, outside the submitted work. Eric Small is a speaker and compensated advisory board member for Janssen, and compensated advisory board member for Fortis Therapeutics and Harpoon Therapeutics. Peter Carroll is on the Advisory Board for Nutcracker Therapeutics and has been a consultant to Insightec. Johannes Czernin is a founder, board member, and holds equity in Sofie Biosciences and Trethera Therapeutics. Intellectual property patented by the University of California is licensed to Sofie Biosciences and Trethera Therapeutics. Johannes Czernin serves on the medical advisory board of Actinium and is a member of the VISION trial steering committee, a clinical trial sponsored by Endocyte. Thomas Hope is a consultant for GE Healthcare and Ipsen, and receives grant support from GE Healthcare. Matthew Rettig is speaker and advisory board member for Janssen and receives research funding from Novartis.

Figures

Figure 1.. STARD Flow Diagram for the Efficacy Cohort with Composite Validation

PET indicates positron emission tomography.

Figure 2.. Detection Rate on a Patient Basis Stratified by PSA and Region

Tr indicates prostate bed only; N1, pelvic nodes only; M1, extrapelvic only. Proportion of patients with 68Ga-PSMA-11 PET positive findings were stratified by PSA range and region of disease in accordance with PROMISE.