PSMA-based PET imaging in newly diagnosed, high-risk localized prostate cancer, a National Cancer Institute (NCI) Cancer Moonshot trial.

327 Background: Prospective randomized trials have suggested that prostate specific membrane antigen (PSMA)-based PET/CT may improve the detection of metastatic disease in patients with high-risk prostate cancer (HR-PCa) diagnosed by conventional imaging. Of patients with HR-PCa who undergo radical prostatectomy (RP), the majority will experience PSA recurrence within 5 years. PSMA-based PET/CT may improve patient selection for local therapy, suggesting that this imaging advancement may be integral to improving patient outcomes. Here, we present results from the NCI cohort of NCT03976843, which evaluated the use of 18F-DCFPyL PSMA- PET/CT in newly diagnosed HR-PCa prior to RP. Methods: Enrolled patients (pts) had HR-PCa (biopsy Gleason score [GS] ≥8, PSA >20, or ≥T3) with negative conventional imaging (CT & bone scan). Pts underwent 18F-DCFPyL PSMA PET/CT and prostate MRI prior to RP. The primary hypothesis was that the subgroup of patients with a negative pre-operative PET/CT would have improved progression-free survival (PFS) over historical controls. Progression was defined as a confirmed PSA ≥ 0.2 ng/mL and PET/CT at progression. Correlatives included IHC of RP specimens and expert NCI radiologic imaging review. Results: Forty patients enrolled, and 38 patients underwent RP. Of the 38, the median age was 68 years old (61-71 years old), median PSA was 8.15 ng/mL (5.75-16.25), median biopsy GS was 8 (8-9), and median RP GS 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, 2 had recurrent pelvic nodal disease, and 9 had no visible disease. No AEs were observed. Conclusions: 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. Expert NCI radiologic review for this multisite study, with correlative molecular and genomic work, is ongoing. Clinical trial information: NCT03976843 .