Evidence Suggesting That Obesity Prevention Measures May Improve Prostate Cancer Outcomes Using Data from a Prospective Randomized Trial

Abstract

Purpose. Increasing body mass index (BMI) is associated with higher risk prostate cancer (PC) at presentation. Whether increasing BMI also prompts earlier salvage androgen suppression therapy (sAST) is unknown. Materials and Methods. Between 1995 and 2001, 206 men with unfavorable risk PC were treated with radiation therapy (RT) or RT and six months of androgen suppression therapy in a randomized controlled trial (RCT). 108 sustained PSA failure; 51 received sAST for PSA approaching 10 ng/mL; 49 with BMI data comprised the study cohort. A multivariable Cox regression analysis identified pretreatment factors associated with earlier sAST receipt. Results. Increasing BMI prompted earlier sAST (median years: 3.7 for overweight/obese, 6.9 for normal weight; adjusted hazard ratio (AHR): 1.11; 95% CI: 1.04, 1.18; P = 0.002) as did high versus other risk PC (median: 3.2 versus 5.2 years; AHR: 2.01; 95% CI: 1.05, 3.83; P = 0.03). Increasing median time to sAST was observed for overweight/obese men with high versus other risk PC and for normal-weight men with any risk PC being 2.3, 4.6, and 6.9 years, respectively (P < 0.001 for trend). Conclusion. Increasing BMI was associated with earlier sAST. A RCT evaluating whether BMI reduction delays or eliminates need for sAST is warranted.

CXCL1 mediates obesity-associated adipose stromal cell trafficking and function in the tumour microenvironment

“…While the role of CXCL8 has been comprehensively studied in the context of prostate cancer and other cancers 42 43 54 , CXCL1 function in cancer remains insufficiently understood. Our study links obesity-dependent CXCL1/CXCR1 gradient activation in the prostate with obesity-dependent cancer progression reported previously 22 23 24 25 26 . Analysis of the tumours of 39 patients undergoing radical prostatectomy for localized disease under our clinical protocol demonstrated that obese patients were more likely than non-obese patients to have lymph node metastases (17 versus 0%, Supplementary Fig.…”

“…Increased adiposity in prostate cancer patients has been identified as a factor associated with disease aggressiveness 22 23 24 25 26 . Tumour stroma, composed of a mixture of various non-malignant cells types, has been identified as one of the drivers of cancer progression 15 18 19 51 52 .…”

“…One of the organs harbouring MSCs capable of stimulating tumours is white adipose tissue (WAT), which is overgrown in obese individuals 14 21 . A number of epidemiological studies have provided evidence that the progression of prostate cancer is associated with obesity 22 23 24 . Increased body mass index (BMI), waist-to-hip ratio (an indicator of abdominal adiposity), as well as overgrowth of periprostatic (PP) WAT are associated with more aggressive tumours and adverse outcome, including mortality 25 26 .…”