Diagnostic Accuracy of 68Ga-PSMA-11 PET for Pelvic Nodal Metastasis Detection Prior to Radical Prostatectomy and Pelvic Lymph Node Dissection: A Multicenter Prospective Phase 3 Imaging Trial

Abstract

Importance: The presence of pelvic nodal metastases at radical prostatectomy is associated with biochemical recurrence after prostatectomy.

Objective: To assess the accuracy of prostate-specific membrane antigen (PSMA) 68Ga-PSMA-11 positron emission tomographic (PET) imaging for the detection of pelvic nodal metastases compared with histopathology at time of radical prostatectomy and pelvic lymph node dissection.

Design, setting, and participants: This investigator-initiated prospective multicenter single-arm open-label phase 3 imaging trial of diagnostic efficacy enrolled 764 patients with intermediate- to high-risk prostate cancer considered for prostatectomy at University of California, San Francisco and University of California, Los Angeles from December 2015 to December 2019. Data analysis took place from October 2018 to July 2021.

Interventions: Imaging scan with 3 to 7 mCi of 68Ga-PSMA-11 PET.

Main outcomes and measures: The primary end point was the sensitivity and specificity for the detection pelvic lymph nodes compared with histopathology on a per-patient basis using nodal region correlation. Each scan was read centrally by 3 blinded independent central readers, and a majority rule was used for analysis.

Results: A total of 764 men (median [interquartile range] age, 69 [63-73] years) underwent 1 68Ga-PSMA-11 PET imaging scan for primary staging, and 277 of 764 (36%) subsequently underwent prostatectomy with lymph node dissection (efficacy analysis cohort). Based on pathology reports, 75 of 277 patients (27%) had pelvic nodal metastasis. Results of 68Ga-PSMA-11 PET were positive in 40 of 277 (14%), 2 of 277 (1%), and 7 of 277 (3%) of patients for pelvic nodal, extrapelvic nodal, and bone metastatic disease. Sensitivity, specificity, positive predictive value, and negative predictive value for pelvic nodal metastases were 0.40 (95% CI, 0.34-0.46), 0.95 (95% CI, 0.92-0.97), 0.75 (95% CI, 0.70-0.80), and 0.81 (95% CI, 0.76-0.85), respectively. Of the 764 patients, 487 (64%) did not undergo prostatectomy, of which 108 were lost to follow-up. Patients with follow-up instead underwent radiotherapy (262 of 379 [69%]), systemic therapy (82 of 379 [22%]), surveillance (16 of 379 [4%]), or other treatments (19 of 379 [5%]).

Conclusions and relevance: This phase 3 diagnostic efficacy trial found that in men with intermediate- to high-risk prostate cancer who underwent radical prostatectomy and lymph node dissection, the sensitivity and specificity of 68Ga-PSMA-11 PET were 0.40 and 0.95, respectively. This academic collaboration is the largest known to date and formed the foundation of a New Drug Application for 68Ga-PSMA-11.

Trial registration: ClinicalTrials.gov Identifiers: NCT03368547, NCT02611882, and NCT02919111.

Conflict of interest statement

Conflict of Interest Disclosures: Dr Hope reported grants from National Cancer Institute (National Institutes of Health [NIH]) and Prostate Cancer Foundation during the conduct of the study; grants from Clovis Oncology and Philips; and personal fees from Curium, Blue Earth Diagnostics, and Ipsen outside the submitted work. Dr Eiber reported personal fees and a cooperation project from Blue Earth Diagnostics and personal fees from Progenics and Point Biopharma outside the submitted work; in addition, Dr Eiber had a patent for rhPSMA issued Scintomics/Blue Earth Diagnostics. Dr Behr reported grants from Commercialization Transition Track (Small Business Innovation Research NIH grant), personal fees from Progenics (honorarium), and personal fees from AAA Novartis (scientific advisory board) outside the submitted work. Dr Zhang reported personal fees from Smith- Kettlewell Eye Research Institute and Raydiant Oximetry, Inc outside the submitted work. Dr Schwarzenböck reported grants from Novartis and personal fees from ABX CRO outside the submitted work. Dr Cooperberg reported personal fees from Janssen, Astellas, AstraZeneca, Dendreon, Merck, Bayer, Foundation Medicine, and Veracyte outside the submitted work. Dr Carroll reported personal fees from Progenics (advisory board) during the conduct of the study; and serving on an advisory board for Nutcracker Therapeutics and receiving personal fees for serving on an advisory board for Insightec outside the submitted work. Dr Herrmann reported research grants from Theragnostics; personal fees from Bayer (speakers bureau, advisory board), Sofie Biosciences (board member, consultant), SIRTEX (speakers bureau), Adacap/Novartis (advisory board, consultant, speakers bureaus), Curium (advisory board, consultant), BTG/BSC (research, advisory board, speakers bureau), Ipsen (advisory board), Siemens Healthineers (speakers bureau, advisory board), GE Healthcare (advisory board), Amgen (advisory board, consultant), Y-mAbs Therapeutics (data monitoring committee), Aktis Oncology (consultant), and Pharma 15 (board member); and nonfinancial support from ABX (consultant) outside the submitted work. Dr Czernin reported being founder and shareholder of Trethera Corporation and Sofie Biosciences. Dr Fendler reported personal fees from RadioMedix, Bayer, Parexel, and BTG outside the submitted work. Dr Calais reported grants from Progenics for PyL Research Access Program, investigator-initiated trial NCT04457245; personal fees (consultant) from POINT Biopharma, Curium Pharma, GE Healthcare, Blue Earth Diagnostics, Janssen Pharmaceuticals, and Progenics; personal fees (blinded independent central reader) from Advanced Accelerator Applications, Radiomedix, Progenics, and Exini; and personal fees (speaker fees) from IBA RadioPharma, and Telix Pharmaceuticals outside the submitted work. No other disclosures were reported.

Figures

Figure.. CONSORT Flow Diagram

PET indicates positron emission tomography; PSMA, prostate-specific membrane antigen; UCLA, University of California, Los Angeles; UCSF, University of California, San Francisco.