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. Experimental Design: The trial prospectively included 37 patients who had an early PSA progression (<= 2 ng/mL) during castration and high-risk (PSA doubling time <= 10 months) non-metastatic disease by conventional imaging. All patients underwent both Ga-68-PSMA and F-18-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 oligo-metastases-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 0.57 ng/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% confidence interval: 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. Nineteen 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 Ga-68-PSMA and F-18-FDG PET, we observed a high prevalence of N+/M+disease and a significant proportion of PSMA-FDG+ disease in patients with an early PSA progression during castration (ChiCTR1900022634).