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.

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

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.

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.

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

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.

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%]).

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.

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

JAMA oncology. 2021 Sep 16 [Epub ahead of print]

Thomas A Hope, Matthias Eiber, Wesley R Armstrong, Roxanna Juarez, Vishnu Murthy, Courtney Lawhn-Heath, Spencer C Behr, Li Zhang, Francesco Barbato, Francesco Ceci, Andrea Farolfi, Sarah M Schwarzenböck, Marcus Unterrainer, Helle D Zacho, Hao G Nguyen, Matthew R Cooperberg, Peter R Carroll, Robert E Reiter, Stuart Holden, Ken Herrmann, Shaojun Zhu, Wolfgang P Fendler, Johannes Czernin, Jeremie Calais

Department of Radiology and Biomedical Imaging, University of California, San Francisco., Ahmanson Translational Theranostics Division, Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles., Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco., Technical University of Munich, School of Medicine, Klinikum rechts der Isar, Department of Nuclear Medicine, Munich, Germany., Division of Nuclear Medicine, IEO European Institute of Oncology IRCCS, Milan, Italy., Division of Nuclear Medicine, Azienda Ospedaliero-Universitaria Di Bologna, Bologna, Italy., Department of Nuclear Medicine, University Medical Centre, Rostock, Germany., Department of Radiology, University Hospital, LMU Munich, Munich, Germany., Department of Nuclear Medicine and Clinical Cancer Research Centre, Aalborg University Hospital, Aalborg, Denmark., Department of Urology, University of California, San Francisco., Institute of Urologic Oncology, University of California, Los Angeles.