Increased Prostate Cancer Glucose Metabolism Detected by 18F-fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in Localised Gleason 8–10 Prostate Cancers Identifies Very High–risk Patients for Early Recurrence and Resistance to Castration

The accuracy of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) to stage prostate cancer (PCa) is limited. However, Gleason 8–10 PCa and more aggressive metastatic PCa have been shown to exhibit a higher glycolytic activity. To evaluate the potential of intraprostatic FDG uptake to prognose Gleason 8–10 PCa patients prior to prostatectomy, based on tumour intrinsic biology. FDG-PET/CT and a bone scan were performed as a staging procedure prior to prostatectomy in 148 consecutive patients diagnosed with PCa with a Gleason sum of ≥8 at biopsy. The FDG-PET/CT images were blind reviewed. Lymph node (LN) metastasis and intraprostatic FDG uptake were systematically recorded, and correlated with the patients’ clinicopathological characteristics. FDG-PET/CT detected foci of intraprostatic FDG uptake in 66% of patients. An intraprostatic FDG uptake of maximum intraprostatic standardised uptake value (SUVmax) of ≥4.6 was statistically significantly associated with a higher pathological Gleason ≥8, extracapsular extension, seminal vesicle invasion, and pathological LN metastasis. In multivariate analysis, an intraprostatic SUVmax of ≥4.6 was associated with a two-fold increased risk of biochemical recurrence in the year following surgery. Patients with an intraprostatic SUVmax of ≥4.6 had estimated median biochemical recurrence-free survival (BFS) of 11.3mo compared with 49.5mo for those with a lower SUVmax. Finally, high intraprostatic FDG uptake was associated with shorter time to castration resistance following radical prostatectomy (RP). Preoperative intraprostatic FDG uptake is an integrator of adverse pathological prognostic factors, predicting BFS and castration resistance following RP in patients with a Gleason score ≥8 PCa at biopsy. These results support the use of preoperative FDG-PET/CT as a tool to distinguish at diagnosis very high–risk Gleason 8–10 PCa patients in whom novel neoadjuvant or adjuvant therapies should be explored. This study shows that an increased use of glucose by prostate cancer cells detected by 18F-fluorodeoxyglucose positron emission tomography molecular imaging can identify aggressive prostate cancers. In Gleason 8–10 prostate cancers, intraprostatic 18F-fluorodeoxyglucose uptake can discriminate, before local therapy, patients at risk of treatment failure and castration resistance. These patients might benefit from upfront adjuvant systemic therapies.