Let food be thy healer, and movement thy shield, before the scalpel entering the field—praise for a pre-prostatectomy diet and exercise program

Obesity and increased visceral fat have been associated with the cause or the exacerbation of many illnesses including but not limited to respiratory issues, hypertension, coronary artery disease and stroke (1). Additionally, obesity is associated with an increased risk of both cancer progression and mortality in colon, kidney, pancreatic and gastric cancers, and more specifically hormone related cancers such as endometrial, breast, and prostate cancer (2).

Bechtel et al. in a phase II randomized controlled trial assessed the effect of weight loss via a weight management program on metabolic and immune-related biomarkers, body composition, and quality of life. In this study, overweight or obese men were randomized to an intervention group that were instructed to follow a calorie-restricted diet along with an exercise and coaching plan prior to radical prostatectomy vs. a control group which was provided standard counseling and educational materials only (3). The program began 4–16 weeks prior to prostatectomy and continued for 6 months after surgery. The intervention group achieved 5.5% weight loss pre-operatively and a net loss of 11% by the end of the study. The intervention group had lower levels of insulin, total cholesterol, low-density lipoprotein, leptin, and visceral adipose tissue. However, no significant changes were in seen in tissue proliferative marker Ki67 or immune markers CXCL12, PDGFRβ or CXCR7. The study intervention participants did report improvements in general and emotional health.

The positive effect of the study program improving metabolic markers and body composition makes complete sense. Weight loss is consistently associated with decreased visceral adipose tissue and insulin resistance profile thus reducing long term cardiovascular risk (4-6). Diet and exercise also logically improve quality of life measures, which may also be derived from the sense of community offered by this program over time. In addition, participating in this program may provide patients with a sense of control over their cancer in a time when they may feel helpless.

The lack of change in circulating or prostate immune-mediated markers is not surprising. While obesity is a state of chronic inflammation with increased cytokines secretion by adipose cells, these interactions are complex and studies correlating these markers in prostate cancer is challenging (7,8). It is possible any true differences cannot be captured by the 5.5% weight decrease seen in this short-term study in a small cohort. Perhaps as patients continue through this program over time, we will see changes between the two groups in their serum immune-mediated biomarker levels.

Importantly, the planned long-term follow-up for biochemical recurrence will provide the key oncologic outcome for this intervention as obese men are at increased risk of biochemical recurrence (9). This program plans to facilitate and maintain weight loss for up to 5 years. The result will be a strong point of motivation when we counsel patients on optimizing their health prior to surgery. Even without a measurable difference in oncologic outcomes, common sense and our body of literature tell us that healthier patients do better peri-operatively and post-operatively. Most surgeons would probably want their patients to enroll in similar programs pre-operatively. In the absence of these thoughtful and resource-intensive programs, the impact of a cancer diagnosis along with careful counseling from the surgeon may provide the impetus for patients to change their lifestyle and improving their health overall.

There are limitations to this study. As this is a randomized control trial, willingness to participate in the trial typically selects for more motivated patients than the average prostatectomy candidate. The study is also not generalizable in that unfortunately the majority of patients do not have access to a multi-session program built by academic dieticians and lifestyle coaches. However, this should be our goal as a healthcare system to work with patients to build sustainable, accessible, community-based programs to improve health in pragmatic ways. In an era of instant gratification and glucagon-like peptide-1 blockers, commitment to programs such as this adds immense long-term value for our patients and this study should be greatly applauded.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Andrology and Urology. The article has undergone external peer review.

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2024-771/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2024-771/coif). The authors have no conflicts of interest to declare.

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References

1. Kopelman P. Health risks associated with overweight and obesity. Obes Rev 2007;8:13-7. [Crossref] [PubMed]
2. Gallagher EJ, LeRoith D. Obesity and Diabetes: The Increased Risk of Cancer and Cancer-Related Mortality. Physiol Rev 2015;95:727-48. [Crossref] [PubMed]
3. Bechtel MD, Michel C, Srinivasan P, et al. Impact of Weight Management on Obesity-Driven Biomarkers of Prostate Cancer Progression. J Urol 2024;211:552-62. [Crossref] [PubMed]
4. Cesaro A, De Michele G, Fimiani F, et al. Visceral adipose tissue and residual cardiovascular risk: a pathological link and new therapeutic options. Front Cardiovasc Med 2023;10:1187735. [Crossref] [PubMed]
5. Magkos F, Fraterrigo G, Yoshino J, et al. Effects of Moderate and Subsequent Progressive Weight Loss on Metabolic Function and Adipose Tissue Biology in Humans with Obesity. Cell Metab 2016;23:591-601. [Crossref] [PubMed]
6. Wing RR, Lang W, Wadden TA, et al. Benefits of modest weight loss in improving cardiovascular risk factors in overweight and obese individuals with type 2 diabetes. Diabetes Care 2011;34:1481-6. [Crossref] [PubMed]
7. Divella R, De Luca R, Abbate I, et al. Obesity and cancer: the role of adipose tissue and adipo-cytokines-induced chronic inflammation. J Cancer 2016;7:2346-59. [Crossref] [PubMed]
8. Grandl G, Wolfrum C. Hemostasis, endothelial stress, inflammation, and the metabolic syndrome. Semin Immunopathol 2018;40:215-24. [Crossref] [PubMed]
9. Rivera-Izquierdo M, Pérez de Rojas J, Martínez-Ruiz V, et al. Obesity and biochemical recurrence in clinically localised prostate cancer: a systematic review and meta-analysis of 86,490 patients. Prostate Cancer Prostatic Dis 2022;25:411-21. [Crossref] [PubMed]