A Prospective Trial of ⁶⁸Ga-PSMA and ¹⁸F-FDG PET/CT in Nonmetastatic Prostate Cancer Patients with an Early PSA...

Tumor heterogeneity and burden, which impact treatment outcome in prostate cancer, are rarely evaluated using next-generation imaging.

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) 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.

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.

Using ⁶⁸Ga-PSMA and ¹⁸F-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).