Associations of periprostatic adipose tissue measures obtained post-androgen deprivation therapy with prostate tumor aggressiveness and gene expression profiles

Abstract Background: Higher periprostatic adipose tissue (PPAT) quantity has been associated with increased prostate cancer aggressiveness. However, PPAT definitions vary between studies, and few examined associations of PPAT with tumor biology. Methods: Using radiation-planning computed tomography scans from 316 prostate cancer patients treated with androgen deprivation therapy at the Northern Ireland Cancer Centre, we contoured PPAT according to three anatomical definitions. Associations of adipose tissue quantity and density (continuous measures and tertiles) with disease aggressiveness (Gleason grade ≥4+3 vs ≤3+4) were examined using logistic regression. Exploratory gene set enrichment analysis identified PPAT-associated pathways enriched in prostate tumors. Results: Among men with prostate cancer, an elevated total quantity of pelvic adipose tissue (ORT3vsT1 1.97; 95%CI 1.10-3.56) and higher density of PPAT in closest proximity to the prostate (ORT3vsT1 2.36; 95%CI 1.00-5.68), were associated with increased odds of high-grade disease. Higher waist circumference was also associated with increased tumor aggressiveness (ORT3vsT1 1.99; 95%CI 1.04-3.86). Men with higher quantity of total pelvic adipose tissue had enriched glucose and lipid signalling-related pathways in their tumors. Conclusions: Greater total pelvic adipose tissue quantity and higher PPAT density were associated with increased tumor aggressiveness among men with prostate cancer. Exploratory analyses identified tumor glucose and lipid metabolism as potential contributing mechanisms. Impact: Our findings support a potential role for PPAT in prostate cancer aggressiveness. Associations of increased PPAT density with higher tumor grade, and of higher quantity of pelvic fat with enhanced tumor glucose and lipid signalling, suggest potential contributing mechanisms to be explored in future studies.