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

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

MATERIALS AND METHODS: Men with prostate cancer recurrence underwent PET/CT 50-70 minutes after intravenous administration of 296±20% MBq 18 F-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.

RESULTS: The overall 18 F-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.

CONCLUSIONS: 18 F-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 18 F-rhPSMA-7.3.