Diagnostic Performance and Safety of 18F-rhPSMA-7.3 PET in Men with Suspected Prostate Cancer Recurrence: Results from a Phase 3, Prospective, Multicenter Study (SPOTLIGHT).

SPOTLIGHT (NCT04186845) evaluated diagnostic performance and safety of radiohybrid (rh) 18F-rhPSMA-7.3, a novel high-affinity PET radiopharmaceutical.

Men with prostate cancer recurrence underwent PET/CT 50-70 minutes after intravenous administration of 296±20% MBq 18F-rhPSMA-7. 3. To assess the co-primary endpoints (verified detection rate [VDR] and combined region-level positive predictive value [crPPV]), 3 blinded, independent central readers evaluated the scans. VDR is equivalent to the overall detection rate (DR) x PPV. Standard of Truth (SoT) was established for each patient using histopathology or confirmatory imaging. Statistical thresholds (lower bounds of the confidence intervals) of 36.5% and 62.5% were prespecified for VDR and crPPV, respectively. Additional endpoints included DR, VDR and crPPV in patients with histopathology SoT, and safety.

The overall 18F-rhPSMA-7.3 DR among all 389 patients with an evaluable scan was 83% (majority read). Among the 366 patients (median PSA, 1.27 ng/mL) for whom a SOT (histopathology [n=69]/confirmatory imaging only [n=297]) was available, VDR ranged from 51% (95%CI, 46.1-56.6) to 54% (95%, 48.8-59.3), exceeding the prespecified statistical threshold. crPPV ranged from 46% (95%CI, 42.0-50.3%) to 60% (95%CI, 55.1-65.5%) across the readers, not meeting the threshold. In the subset of patients with histopathology SoT, the VDR and crPPV were both above the prespecified thresholds (majority read, 81% [95%CI, 69.9-89.6] and 72% [95%CI, 62.5-80.7], respectively). No significant safety concerns were identified.

18F-rhPSMA-7.3 offers a clinically meaningful VDR for localization of recurrent prostate cancer. Despite missing the co-primary endpoint of crPPV, the totality of the data support the potential clinical utility of 18F-rhPSMA-7.3.

The Journal of urology. 2023 Apr 26 [Epub ahead of print]

Ashesh B Jani, Gregory C Ravizzini, Benjamin A Gartrell, Barry A Siegel, Przemyslaw Twardowski, Daniel Saltzstein, Mark T Fleming, Albert Chau, Phillip Davis, Brian F Chapin, David M Schuster

Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia., Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas., Montefiore Medical Center, New York., Division of Nuclear Medicine, Mallinckrodt Institute of Radiology and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, Missouri., John Wayne Cancer Institute, California., Urology San Antonio, Texas., Virginia Oncology Associates, US Oncology Research, Norfolk, Virginia., Blue Earth Diagnostics Ltd, Oxford, United Kingdom., Blue Earth Diagnostics, Burlington, Massachusetts., Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, Texas., Division of Nuclear Medicine and Molecular Imaging, Department of Radiology and Imaging Sciences, Emory University, Atlanta, Georgia.