Evaluating the Heterogeneity of Advanced Prostate Cancer by 18F‐DCFPyL and 18F‐FDG PET/CT in a Prospective Cohort

ABSTRACT Purpose 18 F‐DCFPyL (targeted PSMA) and 18 F‐FDG dual‐tracer PET/CT combination with next‐generation sequencing was applied in a prospective cohort of men with prostate cancer to identify the clinical and genetic characteristics with heterogeneous PET/CT imaging features. Methods 104 men with documented prostate cancer underwent 18 F‐DCFPyL and 18 F‐FDG PET/CT, of which 83 underwent next‐generation sequencing for detecting variation of AR , TP53, RB1, PTEN , etc. Lesions were classified into DCFPyL+FDG± lesions and DCFPyL‐FDG+ lesions and analyzed for heterogeneous distribution. We divided the patients with positive lesions into DCFPyL+FDG± group and DCFPyL‐FDG+ group, then compared the differences in clinical features and genetic mutations between the two groups with CRPC. Results Overall, 92 men had positive lesions detected. By comparing lesion distribution with the DCFPyL+FDG ± , DCFPyL‐FDG+ disease had higher proportions of visceral metastases (4.1% vs. 1.0%, p = 0.002). DCFPyL‐FDG+ was more frequently found in CRPC cohorts, and in the CRPC cohort, patients with DCFPyL‐FDG+ lesions often had worse PSA response. Exploratory analysis showed that TP53 and/or RB1 mutations might be a risk factor for DCFPyL‐FDG+ disease (OR = 10.625, 95% CI 3.492–32.332, p < 0.001). Conclusion Patients with DCFPyL‐FDG+ lesions were more likely to have visceral metastases detected, be found in castration‐resistant cohorts, have TP53 and/or RB1 mutations detected, and have poor therapeutic response compared to patients with DCFPyL+FDG± lesions. Therefore, dual‐tracer ( 18 F‐DCFPyL and 18 F‐FDG) PET/CT is recommended for patients with low PSMA expression incompatible with the true burden of the disease and those with TP53 and/or RB1 mutations to better evaluate the disease burden, tumor heterogeneity, and prognosis.