A prospective trial of 68Ga-PSMA and 18F-FDG PET/CT in nonmetastatic prostate cancer patients with an early PSA progression during castration

Purpose: Tumor heterogeneity and burden, which impact treatment outcome in prostate cancer, are rarely evaluated using next generation imaging. Materials and methods: The trial prospectively included 37 patients who had an early PSA progression (≤2ng/ml)during castration, and high-risk (PSA doubling time ≤10 months) nonmetastatic disease by conventional imaging. All patients underwent both 68Ga-PSMA and 18F-FDG PET/CT. Lesions were classified into PSMA+FDG+/- lesions and PSMA-FDG+ lesions. The primary endpoint was the prevalence of PSMA-FDG+ disease. Tumor burden, predictors for positive imaging and suitability for oligometastases-directed therapy (OMDT) were also evaluated. Results: All patients were treated with RP and the median duration of castration was 23 months. The median PSA at imaging was 0.57ng/ml. Overall, 114 lesions were detected in 29 of the 37 patients. A high prevalence (73%) of N+/M+ disease was observed. Of the 114 lesions, 81 were PSMA+FDG+/- and 33 were PSMA-FDG+. Per patient level, 9 men (24%, 95%CI: 10%-39%) showed at least one new PSMA-FDG+ lesions. A short PSA doubling time (P=0.009, OR=8.000) was associated with PSMA+FDG+/- disease, while a high Gleason grade group (P=0.022, OR=13.091) with PSMA-FDG+ disease. 19 patients (51%) with 51 lesions, including 10 PSMA-FDG+ lesions, could be enrolled for OMDT. Among different disease stages, PSMA-FDG+ disease was rarely detected in the hormone-sensitive cohort, but frequently found in the castration-resistant cohort. Conclusions: Using 68Ga-PSMA and 18F-FDG PET, we observed a high prevalence of N+/M+ disease anda significant proportion of PSMA-FDG+ disease in patients with an early PSA progression during castration. (ChiCTR1900022634)