Obesity and chronic stress have both in prior studies been suggested to influence prostate cancer tumor biology. The mechanisms for this have not been fully described although for obesity, tissue hypoxia inducing systemic inflammation, and for chronic stress, prolonged stimulation of SNS and HPA inducing systemic inflammation as well as immune suppression may increase PCa risk by acting on any emerging or established tumor microenvironment. For obesity, clinical studies on localised PCa have investigated benign and tumor tissue in overweight patients as well as weight loss in presurgical patients.1,3,4 Tumor tissue from obese patients had overexpression of gene sets relating to chromatin remodeling which links to DNA mutational burden,3 whereas weight loss in presurgical patients induced reduced expression of genes related to insulin secretion, and overexpression of DNA repair and immune response genes,1 all of which are biologically advantageous. In the presurgical weight loss study, increased expression of the proliferative biomarker Ki67 was seen, but a follow-up study found this linked to loss of lean muscle, which would be reversed by a weight loss program that includes resistance muscle training.4 Interestingly, another review of chronic stress and it’s influence on PCa racial disparities showed living with chronic stress induced by racism could facilitate SNS and corticosteroid activation, increased expression of inflammatory genes as well as increased alcohol and smoking consumption all of which may contribute to a higher PCa incidence.5
With this in mind, a recent systematic review examined the current evidence for lifestyle programs in prostate cancer patients, focusing on improvements in oncological outcomes and mental health as well as assessing the status of lifestyle biomarkers.2 A total of 75 lifestyle studies were reviewed on cohorts with all stages and disease risks including 15 on mental health outcomes, 44 studies examining oncological outcomes, and 16 on lifestyle biomarkers. The lifestyle interventions were heterogenous in content, timing, and assessment tools, with a broad range of dietary advice, nutritional supplements, exercise programs, and stress reduction activities. The authors comment that this heterogeneity, combined with the range of disease stages and risks in patient groups studied, made meaningful conclusions regarding the influence of lifestyle interventions are challenging. Nevertheless, despite this heterogenous study mixture, there is compelling evidence for their benefit, especially for programs including or focused on moderate to vigorous physical activity. For studies focused on mental health outcomes, 10 out of 15 showed improvements, although, for those studies advocating physical activity alone, the success rate was 7/8. Where included, the diets were vegan or Mediterranean, with one study assessing a smart shirt and mobile app solution for stress reduction. The PA interventions were generally moderate or vigorous exercise (> 3 metabolic equivalent hours per week) from 2 to 12 months and although patients with advanced disease were studied, the majority had localised prostate cancer.2 A total of 44 studies examined the effect of lifestyle programs on oncological outcomes with 26/44 showing a positive benefit, but once again, for programs in which PA was either included or the only intervention, 11/13 studies were successful. 31 of these studies examined diet only including selenium, isoflavones, phytoestrogens, soy, lycopenes, and polyphenol containing foods although their overall success rate was less than 50:50. Again PA interventions were heterogenous, although a number of studies in this category used patient self-reported PA habits with longer follow up (eg sub analyses of CAPSURE and Health Professions Follow Up Studies with 27 years follow up). Oncological outcomes assessed were PSA kinetics, BCR, metastatic progression, and mortality (both cancer specific and overall) and patients cohorts included both localised and advanced disease with a predominance of the former. There were 16 studies reviewed exploring biomarkers potentially affected by lifestyle interventions, including NLRs, PLRs, SII, CRP, NK cells, and inflammatory cytokines based on the links between obesity and systemic inflammation. Although several studies demonstrated links between these markers in patients after lifestyle interventions, the number of patients studied was small, and the findings were inconsistent.
Based on their analysis of all 75 studies the authors concluded that making any specific recommendations was challenging because of the heterogeneity of patient populations, study design, intervention details, and assessment tools. However, adherence to regular moderate to vigorous exercise did seem to consistently improve both mental health and oncological outcomes. The results of certain dietary supplements were promising but inconsistent, and presently more research is required to understand the molecular biology linking obesity to prostate cancer before any biomarkers are found with clinical utility. Nevertheless, the review’s findings support guidelines from, for example, the National Institute of Clinical Excellence (UK), the Center for Disease Control, and the American Cancer Society who are all firm advocates of improved diet and exercise for all cancer patients.
Written by: Zach S Dovey, MD, MBBS, Assistant Professor of Urology at the Icahn School of Medicine, Mount Sinai Health System, New York, NY
References:
- Demark-Wahnefried W, Rais-Bahrami S, Desmond RA, Gordetsky JB, Hunter GR, Yang ES, et al. Presurgical weight loss affects tumour traits and circulating biomarkers in men with prostate cancer. Br J Cancer. 2017;117(9):1303–13.
- Dovey, Z, Horowitz, A, Waingankar, N. The influence of lifestyle changes (diet, exercise and stress reduction) on prostate cancer tumour biology and patient outcomes: A systematic review. BJUI Compass. 2023.
- Ebot EM, Gerke T, Labbé DP, Sinnott JA, Zadra G, Rider JR, et al. Gene expression profiling of prostate tissue identifies chromatin regulation as a potential link between obesity and lethal prostate cancer. Cancer. 2017;123(21):4130–8.
- Frugé AD, Smith KS, Bail JR, Rais-Bahrami S, Demark-Wahnefried W. Biomarkers associated with tumor Ki67 and Cathepsin L gene expression in prostate cancer patients participating in a presurgical weight loss trial. Front Oncol. 2020;10:544201.
- Minas TZ, Kiely M, Ajao A, Ambs S. An overview of cancer health disparities: new approaches and insights and why they matter. Carcinogenesis. 2021;42(1):2–13.
- Plym A, Zhang Y, Stopsack KH, et al. A Healthy Lifestyle in Men at Increased Genetic Risk for Prostate Cancer. Eur Urol. 2023;83(4):343-351.
- Wilson RL, Taaffe DR, Newton RU, Hart NH, Lyons-Wall P, Galvão DA. Obesity and prostate cancer: A narrative review. Crit Rev Oncol Hematol. 2022;169:103543. doi:10.1016/j.critrevonc.2021.103543