Elsevier

European Urology

Volume 63, Issue 5, May 2013, Pages 800-809
European Urology

Platinum Priority – Review – Prostate Cancer
Editorial by Lars Holmberg on pp. 821–822 of this issue
Obesity and Prostate Cancer: Weighing the Evidence

https://doi.org/10.1016/j.eururo.2012.11.013Get rights and content

Abstract

Context

Obesity and prostate cancer (PCa) affect substantial proportions of Western society. Mounting evidence, both epidemiologic and mechanistic, for an association between the two is of public health interest. An improved understanding of the role of this modifiable risk factor in PCa etiology is imperative to optimize screening, treatment, and prevention.

Objective

To consolidate and evaluate the evidence for an epidemiologic link between obesity and PCa, in addition to examining the proposed underlying molecular mechanisms.

Evidence acquisition

A PubMed search for relevant articles published between 1991 and July 2012 was performed by combining the following terms: obesity, BMI, body mass index and prostate cancer risk, prostate cancer incidence, prostate cancer mortality, radical prostatectomy, androgen-deprivation therapy, external-beam radiation, brachytherapy, prostate cancer and quality of life, prostate cancer and active surveillance, in addition to obesity, BMI, body mass index and prostate cancer and insulin, insulin-like growth factor, androgen, estradiol, leptin, adiponectin, and IL-6. Articles were selected based on content, date of publication, and relevancy, and their references were also searched for relevant articles.

Evidence synthesis

Increasing evidence suggests obesity is associated with elevated incidence of aggressive PCa, increased risk of biochemical failure following radical prostatectomy and external-beam radiotherapy, higher frequency of complications following androgen-deprivation therapy, and increased PCa-specific mortality, although perhaps a lower overall PCa incidence. These results may in part relate to difficulties in detecting and treating obese men. However, multiple molecular mechanisms could explain these associations as well. Weight loss slows PCa in animal models but has yet to be fully tested in human trials.

Conclusions

Obesity appears to be linked with aggressive PCa. We suggest clinical tips to better diagnose and treat obese men with PCa. Whether reversing obesity slows PCa growth is currently unknown, although it is an active area of research.

Introduction

Prostate cancer (PCa) is the second most commonly diagnosed cancer and the sixth most common cause of cancer-related mortality among men worldwide [1]. In the last decade, multiple epidemiologic studies have suggested that obesity is associated with increased risk and death from numerous cancer types including PCa [2], [3], [4]. Like PCa, obesity affects many men, with two-thirds of the US classified as overweight (body mass index [BMI] ≥25 kg/m2) and one-third as obese (BMI ≥30 kg/m2). These trends have stabilized in the past 10 yr [5], suggesting these levels are established as a permanent feature of US society. In Europe, the prevalence of overweight and obesity continues to rise, and current levels are comparable with those of the United States 15 yr ago [6].

Because obesity and PCa affect substantial proportions of the male population, the association between the two is of great public health significance. Existing epidemiologic data are somewhat conflicting, and the consolidation and review of findings to date is required. Attention is increasingly turning to the elucidation of underlying molecular mechanisms, a number of which are emerging. This review focuses on the epidemiologic association between obesity and PCa incidence, treatment, and mortality, in addition to proposed underlying molecular mechanisms. It concludes with clinical recommendations for our obese patients. The contribution of specific dietary components, clearly intertwined with obesity, is the focus of our companion review [7]. We previously reviewed the literature on this topic several years ago [8]. At that time, a PubMed search of obesity and PCa generated 237 articles. The same search in July 2012 generated 796 articles, a greater than three-fold increase in the past 5 yr (Fig. 1). Thus we decided an updated review was needed.

Section snippets

Evidence acquisition

Relevant literature published between January 1991 and July 2012 was identified by a search of the PubMed database using the following terms: obesity, BMI, body mass index combined with prostate cancer risk, prostate cancer incidence, prostate cancer mortality, radical prostatectomy, androgen-deprivation therapy, external-beam radiation, brachytherapy, quality of life, active surveillance, and prostate cancer combined with obesity, BMI, body mass index, and insulin, IGF, sex hormones,

Measuring obesity

BMI, calculated using an individual's height and weight (kilograms per square meter), is a straightforward and cost-effective method of measuring overall adiposity. Although BMI does not account for body mass composition or the distribution of adipose tissue, it has been repeatedly demonstrated as a reliable surrogate of obesity on a population level, with the advantage of being the most widely used measure, enabling interstudy comparisons. Thus, due to ease of use and near ubiquitous use in

Conclusions

The epidemiologic association of obesity and aggressive PCa is particularly relevant due to the pervasive nature of both diseases and the large numbers of men affected. Beyond age, race, and family history, there are few established risk factors for PCa. The identification of obesity as an additional risk factor for aggressive PCa is of significant public health interest due to its modifiable nature. Adipose tissue as an organ is unique in its capacity to expand and diminish throughout the

References (98)

  • G. Ploussard et al.

    The risk of upstaged disease increases with body mass index in low-risk prostate cancer patients eligible for active surveillance

    Eur Urol

    (2012)
  • K.Y. Wolin et al.

    Risk of urinary incontinence following prostatectomy: the role of physical activity and obesity

    J Urol

    (2010)
  • S.J. Freedland et al.

    Obesity does not adversely affect health-related quality-of-life outcomes after anatomic retropubic radical prostatectomy

    Urology

    (2005)
  • S.M. Collin et al.

    Prostate-cancer mortality in the USA and UK in 1975–2004: an ecological study

    Lancet Oncol

    (2008)
  • J. Ma et al.

    Prediagnostic body-mass index, plasma C-peptide concentration, and prostate cancer-specific mortality in men with prostate cancer: a long-term survival analysis

    Lancet Oncol

    (2008)
  • A.G. Renehan et al.

    Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis

    Lancet

    (2004)
  • G. Williams

    Aromatase up-regulation, insulin and raised intracellular oestrogens in men, induce adiposity, metabolic syndrome and prostate disease, via aberrant ER-alpha and GPER signalling

    Mol Cell Endocrinol

    (2012)
  • A. Morgentaler

    Testosterone and prostate cancer: an historical perspective on a modern myth

    Eur Urol

    (2006)
  • H. Bonkhoff et al.

    The evolving role of oestrogens and their receptors in the development and progression of prostate cancer

    Eur Urol

    (2009)
  • P. Somasundar et al.

    Prostate cancer cell proliferation is influenced by leptin

    J Surg Res

    (2004)
  • S.J. Freedland et al.

    Serum leptin and pathological findings at the time of radical prostatectomy

    J Urol

    (2005)
  • S. Goktas et al.

    Prostate cancer and adiponectin

    Urology

    (2005)
  • S.F. Shariat et al.

    Plasma levels of interleukin-6 and its soluble receptor are associated with prostate cancer progression and metastasis

    Urology

    (2001)
  • K. Fizazi et al.

    Randomised phase II study of siltuximab (CNTO 328), an anti-IL-6 monoclonal antibody, in combination with mitoxantrone/prednisone versus mitoxantrone/prednisone alone in metastatic castration-resistant prostate cancer

    Eur J Cancer

    (2012)
  • D.S. Finley et al.

    Periprostatic adipose tissue as a modulator of prostate cancer aggressiveness

    J Urol

    (2009)
  • Y. Liu et al.

    Does physical activity reduce the risk of prostate cancer? A systematic review and meta-analysis

    Eur Urol

    (2011)
  • E.E. Calle et al.

    Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults

    N Engl J Med

    (2003)
  • G.K. Reeves et al.

    Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study

    BMJ

    (2007)
  • K.M. Flegal et al.

    Prevalence and trends in obesity among US adults, 1999–2008

    JAMA

    (2010)
  • A. Berghofer et al.

    Obesity prevalence from a European perspective: a systematic review

    BMC Public Health

    (2008)
  • R.J. MacInnis et al.

    Body size and composition and prostate cancer risk: systematic review and meta-regression analysis

    Cancer Causes Control

    (2006)
  • A. Bergstrom et al.

    Overweight as an avoidable cause of cancer in Europe

    Int J Cancer

    (2001)
  • J. Baillargeon et al.

    Obesity, adipokines, and prostate cancer in a prospective population-based study

    Cancer Epidemiol Biomarkers Prev

    (2006)
  • A. Engeland et al.

    Height, body mass index, and prostate cancer: a follow-up of 950000 Norwegian men

    Br J Cancer

    (2003)
  • S.O. Andersson et al.

    Body size and prostate cancer: a 20-year follow-up study among 135006 Swedish construction workers

    J Natl Cancer Inst

    (1997)
  • M.P. Porter et al.

    Obesity and the risk of prostate cancer

    Prostate

    (2005)
  • Z. Gong et al.

    Obesity, diabetes, and risk of prostate cancer: results from the prostate cancer prevention trial

    Cancer Epidemiol Biomarkers Prev

    (2006)
  • C. Rodriguez et al.

    Body mass index, weight change, and risk of prostate cancer in the Cancer Prevention Study II Nutrition Cohort

    Cancer Epidemiol Biomarkers Prev

    (2007)
  • M.E. Wright et al.

    Prospective study of adiposity and weight change in relation to prostate cancer incidence and mortality

    Cancer

    (2007)
  • L.L. Banez et al.

    Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer

    JAMA

    (2007)
  • I.A. Hekal et al.

    Obesity-PSA relationship: a new formula

    Prostate Cancer Prostatic Dis

    (2010)
  • J. Baillargeon et al.

    The association of body mass index and prostate-specific antigen in a population-based study

    Cancer

    (2005)
  • R.L. Grubb et al.

    Serum prostate-specific antigen hemodilution among obese men undergoing screening in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial

    Cancer Epidemiol Biomarkers Prev

    (2009)
  • D.I. Chu et al.

    Predictive value of digital rectal examination for prostate cancer detection is modified by obesity

    Prostate Cancer Prostatic Dis

    (2011)
  • C. Rodriguez et al.

    Body mass index, height, and prostate cancer mortality in two large cohorts of adult men in the United States

    Cancer Epidemiol Biomarkers Prev

    (2001)
  • Y. Cao et al.

    Body mass index, prostate cancer-specific mortality, and biochemical recurrence: a systematic review and meta-analysis

    Cancer Prev Res (Phila)

    (2011)
  • S.J. Freedland et al.

    Obesity and oncological outcome after radical prostatectomy: impact of prostate-specific antigen-based prostate cancer screening: results from the Shared Equal Access Regional Cancer Hospital and Duke Prostate Center databases

    BJU Int

    (2008)
  • G.S. Merrick et al.

    Obesity is not predictive of overall survival following permanent prostate brachytherapy

    Am J Clin Oncol

    (2007)
  • C.J. Keto et al.

    Obesity is associated with castration-resistant disease and metastasis in men treated with androgen deprivation therapy after radical prostatectomy: results from the SEARCH database

    BJU Int

    (2011)
  • Cited by (0)

    Please visit www.eu-acme.org/europeanurology to read and answer questions on-line. The EU-ACME credits will then be attributed automatically.

    View full text