Trials for Prostate Specific Membrane Antigen (PMSA)-Based PET Imaging of High Risk Prostate Cancer

Division Of Basic Sciences - Nci

Investigators

Abstract

During FY2025, major activities have been accomplished for this clinical research project. At the NCI, 40 participants were enrolled and 38 participants underwent RP. Enrolled participants had HR-PCa (biopsy Gleason Score greater than or equal to 8, PSA greater than 20, or greater than or equal to T3 staging) with negative conventional imaging (CT and bone scan). Participants underwent 18F-DCFPyL PSMA PET/CT and prostate MRI prior to RP. Specific objectives include blinded radiographic imaging reads of the MRIs and PSMAs by the Molecular Imaging Branch (MIB). This is ongoing through intramural collaborators in MIB. Histologic analysis was also completed on 38 RP samples. For the 38 participants that underwent RP , the median age was 68 years old (61-71 years old), median PSA was 8.15 ng/mL (5.75-16.25), median biopsy Gleason Score was 8 (8-9), and median RP Gleason Score was 7 (7-8). Pre-operative PET/CT demonstrated regional lymphadenopathy in 2 patients (5.3%), and the median SUVmax of the index lesion was 12.6 (6.6-17.1). At a median follow-up of 2.2 years, the 2- and 4-year PFS was 76% (63%-91%) and 45% (22%-95%), respectively. The median PFS was 3.2 years. Of the 11 pts who underwent progression restaging with a second PSMA PET/CT, 2 had recurrent pelvic nodal disease, and 9 had no visible disease. No toxicities were observed secondary to the tracer used in the PSMA PET/CT imaging. Expression of PSMA was modestly correlated with SUVmax values on PSMA PET/CT. Expression of PSMA was heterogenous and disconcordant cases between IHC and SUVmax highlight that IHC is not a complete surrogate for ligand binding avidity for 18F-DCPyL. These results support 18F-DCFPyL PET/CT as a safe and effective pre-operative staging strategy with the potential to improve patient selection for local definitive therapy. MIB radiologic review for the additional patients on this study with correlative molecular and genomic work, is ongoing.