Abdominal and pelvic adipose tissue distribution and risk of prostate cancer recurrence after radiation therapy

Abstract

Background Fat distribution varies between individuals of similar body mass index (BMI). We hypothesized that visceral obesity is more strongly associated with poor prostate cancer outcomes than overall obesity defined by BMI. Materials and Methods We quantified abdominal visceral and subcutaneous fat area (VFA and SFA), and pelvic periprostatic adipose tissue area (PPAT), using computed tomography scans from radiation‐treated prostate cancer patients at the Durham North Carolina Veterans Administration Hospital. Multivariable‐adjusted Cox regression examined associations between each adiposity measure and risk of recurrence, overall and stratified by race and receipt of androgen deprivation therapy (ADT). Results Of 401 patients (59% black) treated from 2005 to 2011, 84 (21%) experienced recurrence during 9.3 years median follow‐up. Overall, obesity defined by BMI was not associated with recurrence risk overall or stratified by race or ADT, nor was any measure of fat distribution related to the risk of recurrence overall or by race. However, higher VFA was associated with increased risk of recurrence in men who received radiation only (hazard ratio [HR], 1.79; 95% confidence interval [CI], 0.87‐3.66), but inversely associated with recurrence risk in men treated with radiation and ADT (HR, 0.49; 95% CI, 0.24‐1.03; P‐interaction = .002), though neither association reached statistical significance. Similar patterns of ADT‐stratified associations were observed for PPAT and SFA. Conclusions Associations between abdominal and pelvic adiposity measures and recurrence risk differed significantly by ADT receipt, with positive directions of association observed only in men not receiving ADT. If confirmed, our findings suggest that obesity may have varying effects on prostate cancer progression risk dependent on the hormonal state of the individual.

Associations of fat and muscle mass with overall survival in men with prostate cancer: a systematic review with meta-analysis

“…Sarcopenia has become a topic of great interest in oncology [68]; however, poorly understood given the lack of reporting on assessment characteristics and definitions. For example, although studies had reported the time of body composition assessment [25,33,34,36,37,[40][41][42][43]45], the high heterogeneity and lack of standardisation could misclassify prostate cancer patients with obesity or sarcopenia and, therefore, mask the impact of these outcomes on overall survival. Future research should better inform definitions (i.e., cut-off values and rationale) and time of assessments, and information about clinical factors associated with muscle mass accrual or maintenance in this group of patients.…”

“…1 and Supplementary eAppendix 2). A total of 16 cohort studies undertaking retrospective analyses [16,24,25,[33][34][35][36][37][38][39][40][41][42][43][44][45] were included in the primary analysis. During the eligibility assessment, six additional studies [46][47][48][49][50][51] were initially selected and authors contacted given the lack of specific information on the results for prostate cancer patients.…”

“…In summary, a total of 4807 prostate cancer patients with a median age of 69.0 years (interquartile range (IQR): 67.2-71.3) and BMI of 26.6 kg m −2 (IQR: 24.3-28.7) participated in the included studies. All studies except one derived fat and muscle mass measures from CT scans [16,24,25,[34][35][36][37][38][39][40][41][42][43][44][45]. Most studies (n = 11) included advanced prostate cancer patients (e.g., metastatic, castration-resistant or metastatic castration-resistant patients) [16,24,34,35,38,39,[41][42][43][44][45], and the majority of patients received treatments such as radiotherapy [33,[36][37][38][39][40][41][42][43] and ADT [33,[35][36][37][40][41][42][43][44] (n = 9 for both), followed by surgery [25,33,…”

“…Eight studies [24, 33-35, 40, 43-45] [40]) [24,35,40,43,45], three studies examining VAT/ SAT ratio (with one study reporting a cut-off of 1.0 [44]) [34,44,45] and one study examining whole-body fat mass [33]. Given that six studies [24,34,35,40,43,45] undertook multivariable models controlling for BMI (median number of covariates of 7.0, ranging from 2 to 12; with two studies also controlling for muscle mass measures [24,43]), the results from the meta-analysis provided no differences in overall survival (HR 0.98, p = 0.888; Table 3) in a sample of 1697 prostate cancer patients. The heterogeneity was I 2 = 70%.…”

A Scoping Review on Lipocalin-2 and Its Role in Non-Alcoholic Steatohepatitis and Hepatocellular Carcinoma

“…On an organism scale, obesity is found to promote tumorigenesis through elevated levels of adipokines, growth factors, steroid hormones, chronic inflammation producing reactive oxygen species (ROS), and a change in gut microbiota [84]. For example, it has been proven that accumulated visceral fat, which is a hallmark of obesity, correlates with primary tumor recurrence, poor prognosis, and chemotherapeutic resistance [85,86] In that setting, adipose tissue plays a significant role by excreting adipokines, with LCN2 being one of them. Some authors even suggest that LCN2 expressed by adipose tissue causes the activation of both MMP-2 and MMP-9, which are promoters of tumorigenesis, and they found especially increased circulating concentrations of the LCN2/MMP-9 complex, which is known for its tissue remodeling properties [87].…”