Changes in periprostatic adipose tissue induced by 5α‐reductase inhibitors

Abstract

There is increasing interest in periprostatic fat and its influence on prostate cancer aggressiveness. In vitro data suggest that adipose stromal/stem cells (ASCs) can increase production of cytokines and growth factors resulting in invasive growth and metastasis in prostate cancer. The objective of the study was to determine the interaction between 5α-reductase inhibitors (5ARIs) and periprostatic adipose tissue (PPAT) and factors of prostate cancer aggressiveness. In this retrospective study, we identified 61 patients treated with 5ARIs for a period of ≥12 months before undergoing radiation therapy (brachytherapy or external beam radiotherapy). The control group consisted of 117 patients without any exposure to 5ARIs. Prior to being treated, all patients underwent abdominal computed tomography (CT). To measure PPAT, we defined the fat pad anteriorly to the prostate, as well as the intra-abdominal visceral adipose tissue (VAT) and subcutaneous tissue (SAT) at the level of L4/L5. All contours were performed manually. These adipose tissue measurements were correlated with the Cancer of the Prostate Risk Assessment (CAPRA) score using Pearson correlation coefficient. Differences in fat contents were evaluated using Student's t-test. Median time on 5ARIs for the 61 patients was 12 months (range 12-96). Patient on 5ARIs had a significantly (p < 0.001) smaller PPAT (0.4, SD 0.5) than patients without a 5ARI (0.6 cc, SD 0.4). There was no significant correlation between the CAPRA score and fat measurements when adjusted for 5ARI use (p = 0.18). In non-5ARI users, BMI was not correlated with PPAT but was correlated with SAT and VAT volume and its density. There were no significant differences in diabetics (p = 0.3), metformin users (p = 0.4) or statin users (p = 0.09) between both groups. 5ARIs taken for at least 12 months induce changes in PPAT volume. Whether these changes or the extent of changes will have an influence on outcome remains unknown.

Peri‐prostatic adipose tissue: the metabolic microenvironment of prostate cancer

“…The accumulated weight of evidence to date supports an association between PPAT quantity and increased PCa aggressiveness, although the mechanistic basis of this association remains inconclusive and has limited the development of potential interventions. Measuring PPAT area or density showed more significant correlations with PCa aggressiveness than measuring general obesity markers BMI and waist circumference , while the correlation of PPAT thickness with BMI or weight was non‐significant or weak . Moreover, no association has been demonstrated between subcutaneous adipose thickness and PCa aggressiveness ; thus, PPAT measurements may serve as an independent predictor of PCa aggressiveness rather than as a surrogate measure for body adiposity.…”

“…Most recently, Taussky et al. defined PPAT as the adipose bed located only anteriorly to the prostate gland in a CT section at the level of the intervertebral space at the L4 and L5 level. The authors reported no significant correlation between BMI and PPAT volume and density, nor between PPAT and PCa aggressiveness, as defined by Cancer of the Prostate Risk Assessment (CAPRA) score.…”

Assessment of Periprostatic and Subcutaneous Adipose Tissue Lipolysis and Adipocyte Size from Men with Localized Prostate Cancer

“…Importantly, others have shown that there was no difference in patient-derived xenografts of moderate-grade localized PCa tumorigenicity in lean and high-fat diet-induced obese severe combined immunodeficiency (SCID) mice [ 77 ]. It is important to note that PPAT thickness, as measured by MRI or similar techniques, does not correlate with BMI [ 78 ] and so the relationship between patient obesity, PPAT, and PCa biology remains complex and unresolved.…”

Prognostic Value of CT-Attenuation and 18F-Fluorodeoxyglucose Uptake of Periprostatic Adipose Tissue in Patients with Prostate Cancer

“…Considering that no significant correlation between BMI and either PPAT HU or SUV was observed in our study, these inconsistent results might be due to the confounding effects of qualitative features of PPAT. Recently, an attempt has been made to pharmacologically modify PPAT features with 5α-reductase inhibitors and estrogen, which is expected to affect the outcomes of prostate cancer [49,50]. Based on the results of the present study, PPAT HU and SUV might be used to select candidates and to monitor treatment response to future therapy that targets PPAT in patients with prostate cancer.…”