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

Abstract

Background: 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.

Objective: To evaluate the potential of intraprostatic FDG uptake to prognose Gleason 8-10 PCa patients prior to prostatectomy, based on tumour intrinsic biology.

Design, setting, and participants: 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.

Outcome measurements and statistical analysis: 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.

Results and limitations: 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).

Conclusions: 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.

Patient summary: 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.

Keywords: (18)F-fluorodeoxyglucose; Castration resistance; Failure to local therapies; High-grade prostate cancer; High-risk prostate cancer; Positron emission tomography.