Monday, March 10, 2014

Obesity and Urological Malignancies: Understanding the Impact

More than 1 in 3 adults in the United States are classified as obese, as defined by a Body Mass Index (BMI) greater than 30 kg/m2 [1]. Obese patients have been shown to be at an increased risk for a variety of health problems including cardiovascular disease, diabetes, and many types of cancer [2]. Significant evidence has demonstrated that obesity has a tremendous impact on the incidence and treatment outcomes of the most common types of genitourinary cancers.

Here we review the link between obesity and cancers of the bladder, kidney and prostate.

BLADDER

Several studies have attempted to demonstrate a definitive link between obesity and an increased incidence of urothelial carcinoma of the bladder. Two analyses of high-volume patient populations published in 2007-2008 showed conflicting data; one demonstrated a statistically significant increased risk for bladder cancer with increasing BMI while the other showed no correlation [3, 4].

Despite the lack of a definitive connection between obesity and the incidence of bladder cancer, there is a substantial amount of literature detailing that obesity has a clear impact on rates of operative complications and treatment outcomes. Patients with a BMI greater than 40 kg/m2 more frequently undergo incontinent urinary diversions rather than procedures that preserve continence at the time of radical cystectomy [5]. Additionally, patients with higher BMI are at increased risk for complications both during and after a procedure, and have been shown to have longer operative times and more blood loss during surgery [5-7]. Despite the increased risk of surgical complications, however, evidence has shown that there is no association between obesity and decreased survival following a radical cystectomy [6, 8].

KIDNEY

Renal cell carcinoma (RCC), which accounts for more than 90% of all kidney cancer cases, has been clearly demonstrated to have an increased incidence in the obese population [9]. A 2001 study summarized the findings of 22 prior reports, concluding that for every increase of 1 kg/m2 in BMI there was a 7% increase in the relative risk of having RCC (RR=1.07) [10]. Biologic changes at the molecular level may contribute to this observed association between obesity and kidney cancer. Specifically, metabolism and breakdown of lipid stores, which are increased in obese patients, have been shown to increase the amount of DNA damage in certain kidney cells. This DNA damage is thought to increase the risk of inactivation of genes, such as VHL, that prevent cells from ultimately becoming cancerous [11].

Interestingly, multiple studies have shown that obese patients with RCC have an improved survival following nephrectomy when compared with patients who have a normal BMI [12-14]. This phenomenon has been labeled the "obesity paradox."[15] One such analysis postulated that this survival advantage may be due to less aggressive and more localized cancers in obese patients at presentation, though this has yet to be definitively demonstrated [14].

PROSTATE

The relationship between obesity and prostate cancer has been widely studied. In 2006 a summary of 56 studies showed that there was a slight overall increased relative risk of prostate cancer with increasing BMI (RR=1.06 per 5 kg/m2 increase in BMI). This study also found that obese patients were at a significantly increased risk of developing advanced stage prostate cancer (RR=1.12 per 5 kg/m2 increase in BMI) [16].

Why do obese patients tend to present with more aggressive cancers? First, obese patients with prostate cancer are diagnosed later than patients with a normal BMI. A larger body habitus may make an accurate digital rectal examination more difficult to perform, leading to decreased detection rates. In addition, data has shown that in patients with diagnosed prostate cancer, PSA levels decrease as BMI increases, suggesting that the results of PSA testing may be complicated by obesity [17]. Thus, obese patients with prostate cancer are more likely to have PSA concentrations below the typical values suspicious for cancer in a patient with normal BMI, contributing to further decreased detection rates. Finally, several biologic mechanisms at the cellular level have been proposed to account for the increased incidence of aggressive cancers seen in the obese population. Excess fatty tissue in obese patients has been shown to lead to increased levels of several hormones in the blood, including insulin and IGF-1. These hormones have been shown in experimental animal models to increase growth rates in tumor cells, and it is thought that a similar effect occurs in humans with obesity [18].

Multiple studies have shown that obesity is associated with poorer treatment outcomes following prostatectomy, as obese patients have an increased risk of positive surgical margins and recurrence of PSA levels [19]. It has also been shown that procedures done on obese patients have lower rates of successful nerve sparing, leading to worse erectile function outcomes and impaired quality of life [20]. Ultimately, obese patients with prostate cancer in two large trials were shown to have a significantly increased cancer-specific mortality rate (RR=1.21-1.27) [21].

SUMMARY


  • Obesity has been shown to increase the risk of developing renal cell carcinoma and aggressive prostate cancer, while its influence on the risk of bladder cancer remains less clear.
  • Obesity is associated with poorer treatment outcomes in bladder and prostate cancer including increased rates of operative complications.
  • Obesity has been shown to have varying effects on survival in cancers of the bladder (no effect), kidney (improved survival) and prostate (worsened survival).
  • Biologic mechanisms have been implicated in the link between obesity and both kidney and prostate cancers.
  • Lifestyle modification via weight reduction and exercise is important as it may reverse the increased risk for genitourinary cancers and improve treatment outcomes [22].


This blog was written by Jack Cooper, medical student at Johns Hopkins Medical School.  Jack recently finished a four-week sub-internship at the Brady Urological Institute and gave a presentation to the department on "Obesity and Genitourinary Malignancies" from which this blog is inspired.  Jack is looking forward to a career in urology.







[1] Ogden CL, Carroll MD Kit BK, Flegal KM. Prevalence of obesity in the United States, 2009-2010. NCHS Data Brief, Jan 2012.
[2] Calle EE. Obesity and cancer. BMJ 2007; 335:1107.
[3] Koebnick C, Michaud D, Moore SC, et al. Body mass index, physical activity, and bladder cancer in a large prospective study. Cancer Epidemiol Biomarkers Prev. 2008 May;17(5):1214-21.
[4] Holick CN, Giovannucci EL, Stampfer MJ, Michaud DS. Prospective study of body mass index, height, physical activity, and incidence of bladder cancer in U.S. men and women. Int J Cancer. 2007 Jan 1; 120(1):140-6.
[5] Lee CT, Dunn RL, Chen BT, et al. Impact of body mass index on radical cystectomy. J Urol. 2004 Oct;172(4 Pt 1):1281-5.
[6] Maurer T, Maurer J, Retz M, et al. Influence of body mass index on operability, morbidity and disease outcome following radical cystectomy. Urol Int. 2009;82(4):432-9.
[7] Chang SS, Jacobs B, Wells N, et al. Increased body mass index predicts increased blood loss during radical cystectomy. J Urol. 2004 Mar;171(3):1077-9.
[8] Hafron J, Mitra N, Dalbagni G, et al. Does body mass index affect survival of patients undergoing radical or partial cystectomy for bladder cancer? J Urol. 2005 May;173(5):1513-7.
[9] Li L, Kaelin WG Jr. New insights into the biology of renal cell carcinoma. Hematol Oncol Clin North Am. 2011 Aug;25(4):667-86.
[10] Bergstrom A, Hsieh CC, Lindblad P, et al. Obesity and renal cell cancer—a quantitative review. Br J Cancer. 2001 Sep 28;85(7):984-90.
[11] Gago-Dominguez M, Castelao JE, Yuan JM, et al. Lipid peroxidation: A novel and unifying concept of the etiology of renal cell carcinoma. Cancer Causes Control. 2002 Apr;13(3):287-93.
[12] Haferkamp A, Pritsch M, Bedke J, et al. The influence of body mass index on the long-term survival of patients with renal cell carcinoma after tumour nephrectomy. BJU Int. 2008 May;101(10):1243-6.
[13] Kamat AM, Shock RP, Naya Y, et al. Prognostic value of body mass index in patients undergoing nephrectomy for localized renal tumors. Urology. 2004 Jan;63(1):46-50.
[14] Parker AS, Lohse CM, Cheville JC, et al. Greater body mass index is associated with better pathologic features and improved outcome among patients treated surgically for clear cell renal cell carcinoma. Urology. 2006 Oct;68(4):741-6.
[15] Hakimi AA1, Furberg H, Zabor EC, Jacobsen A, Schultz N, Ciriello G, Mikklineni N, Fiegoli B, Kim PH, Voss MH, Shen H, Laird PW, Sander C, Reuter VE, Motzer RJ, Hsieh JJ, Russo P.  An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma.J Natl Cancer Inst. 2013 Dec 18;105(24):1862-70. doi: 10.1093/jnci/djt310. Epub 2013 Nov 27.
[16] Macinnis, RJ, English DR. Body size and composition and prostate cancer risk: systematic review and meta-regression analysis. Cancer Causes Control. 2006 Oct;17(8):989-1003.
[17] Banez LL, Hamilton RJ, Partin AW, et al. Obesity-related plasma hemodilution and PSA concentration among men with prostate cancer. JAMA. 2007 Nov 21;298(19):2275-80.
[18] Calle EE, Kaaks R. Overweight, obesity, and cancer: Epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004 Aug; 4(8):579-91.
[19] Freedland SJ, Aronson WJ, Kane CJ, et al. Impact of obesity on biochemical control after radical prostatectomy for clinically localized prostate cancer: a report by the Shared Equal Access Regional Cancer Hospital database study group. J Clin Oncol. 2004 Feb 1;22(3):446-53.
[20] Sundi D, Reese AC, Mettee LZ, et al. Laparoscopic and robotic radical prostatectomy outcomes in obese and extremely obese men. Urology. 2013 Sep;82(3):600-5.
[21] Rodriguez C, Patel AV, Calle EE, 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 Apr;10(4):345-53.
[22] Chu KF, Rotker K, Ellsworth P. The impact of obesity on benign and malignant urologic conditions. Postgrad Med. 2013 Jul; 125(4):53-69.

2 comments:

  1. I just want to share this personal story about how my husband survived the problem of NO ERECTION after prostate surgery.
    My husband undertook prostate surgery 3 years ago and before then i always looked forward to great sex with him and after the surgery he was unable to achieve any erections, we were bothered and we tried so many drugs, injections and pumps and rings but none could give him an erection to even penetrate. I searched for a cure and got to know about Dr. Hillary who is renowned for curing problems of this nature and he did encouraged me not to give up and he recommended his herbal medication which my hubby took for 3 weeks and today his sexual performance is optimum. You too can contact him for similar problems on hillaconn@gmail.com. A man who cannot satisfy his wife's sexual need is not a real man!

    ReplyDelete