Impact of Weight Management on Obesity-Driven Biomarkers of Prostate Cancer Progression

Abstract

Purpose: Excess body and visceral fat increase the risk of death from prostate cancer (PCa). This phase II study aimed to test whether weight reduction by > 5% total body weight counteracts obesity-driven PCa biomarkers.

Materials and methods: Forty men scheduled for prostatectomy were randomized into intervention (n = 20) or control (n = 20) arms. Intervention participants followed a weight management program for 4 to 16 weeks before and 6 months after surgery. Control participants received standardized educational materials. All participants attended visits at baseline, 1 week before surgery, and 6 months after surgery. Circulating immune cells, cytokines, and chemokines were evaluated. Weight loss, body composition/distribution, quality of life, and nutrition literacy were assessed. Prostate tissue samples obtained from biopsy and surgery were analyzed.

Results: From baseline to surgery (mean = 5 weeks), the intervention group achieved 5.5% of weight loss (95% CI, 4%-7%). Compared to the control, the intervention also reduced insulin, total cholesterol, LDL cholesterol, leptin, leptin:adiponectin ratio, and visceral adipose tissue. The intervention group had reduced c-peptide, plasminogen-activator-inhibitor-1, and T cell count from baseline to surgery. Myeloid-derived suppressor cells were not statistically different by group. Intervention group anthropometrics improved, including visceral and overall fat loss. No prostate tissue markers changed significantly. Quality of life measures of general and emotional health improved in the intervention group. The intervention group maintained or kept losing to a net loss of 11% initial body weight (95% CI, 8%-14%) at the study end.

Conclusions: Our study demonstrated improvements in body composition, PCa biomarkers, and quality of life with a weight management intervention.

Keywords: obesity; prostate cancer; quality-of-life; visceral fat; weight loss.

Figure 1.

Study schema showing the different intervention phases and timing of assessments. The same assessments were measured and analyzed in all participants at their study visits occurring at baseline, within 1 week prior to radical prostatectomy, and 6 months after radical prostatectomy using the tools/instruments described in the feasibility study. Anthropometrics were conducted in a hospital gown without shoes using standardized procedures. Body weight was taken on the same scale, and body composition was measured using a dual-energy x-ray absorptiometry Lunar GE. Two 24-hour diet recalls were obtained and averaged together for dietary intake analysis. Nutrient intake was analyzed using Nutrition Data System for Research software version 2017. Dietary intake was also scored using the Alternative Healthy Eating Index. Nutrition literacy was assessed using the Nutrition Literacy Assessment Instrument at baseline and final visits only. The Expanded Prostate Cancer Index Composite survey was administered at the final study visit and at 1 year after radical prostatectomy. Coaches and participants interacted in real time using a health platform to communicate for better adherence, monitoring, and reinforcement. The intervention participants tracked body weight, diet intake, exercise, and adverse events in the m.Care app platform from LifeScience Technologies, customized specifically for our study and codeveloped with input from our pilot study participants. Intervention participants met weekly with a registered dietitian to adjust energy targets based on rate of weight loss, hunger, or fatigue with an initial target at 25% below estimated energy requirements. Coaching sessions focused on goal-setting, self-monitoring, discussing progress, overcoming obstacles, adjusting diet/exercise plans, teaching nutrition and exercise strategies. Intervention participants also had a midweek coaching phone check-in during the weight loss phase. In the weight maintenance phase, intervention participants met weekly by phone with their dietitian and attended 4 group educational classes. Intervention and control groups received the “Heal Well Cancer Nutrition Guide” from the American Institute of Cancer Research and Dr Walsh’s book, “Guide to Surviving Prostate Cancer.” The books were recommended by the ambassadors from the feasibility study (previous research participants) because they felt it was important to offer helpful education to the control group that would not affect the study outcomes.

Figure 2.

CONSORT diagram for the WARRIOR study.

Figure 3.

Waterfall plot showing the individual percent weight loss from baseline to study end. The dotted line represents the 5% weight loss goal to achieve clinically significant weight change.