UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Chemoprevention of urothelial carcinoma of the bladder

Authors
Juan Antonio Jiménez, MD, PhD
Steven C Campbell, MD, PhD
Section Editors
Jerome P Richie, MD, FACS
Seth P Lerner, MD
Deputy Editor
Michael E Ross, MD

INTRODUCTION

Urothelial carcinoma of the bladder, the most common malignancy of the urinary tract, is the fourth most common malignancy in men and the tenth most common malignancy in women. (See "Epidemiology and risk factors of urothelial (transitional cell) carcinoma of the bladder", section on 'Risk factors'.)

The majority of cases of urothelial carcinoma of the bladder can be attributed to smoking and occupational and environmental carcinogen exposures, which cause diffuse changes in the urothelium and eventually result in bladder cancer. The identification of these risk factors provides an opportunity to minimize the incidence of bladder cancer through smoking cessation programs and decreasing exposure to workplace carcinogens [1-3].

Other potentially useful approaches include increasing cruciferous vegetable [4] and fluid intake [5], decreasing dietary fat [6], and losing weight [7]. Any of these factors must be placed in the context of possible predisposing genetic factors, which are poorly understood [8].

Chemoprevention is the use of systemic agents to prevent or reverse these changes. Primary chemoprevention seeks to block the formation of de novo bladder cancers in healthy individuals, while secondary chemoprevention focuses on avoiding formation of additional tumors in patients who have already been treated for bladder cancer. Although chemoprevention is not routinely recommended in either primary or secondary settings, it is an area of active clinical investigation.

The chemoprevention of bladder cancer with systemic agents is reviewed here, with the focus primarily on agents for which epidemiologic or clinical trial data are available. The use of intravesical agents to prevent the recurrence of non-muscle invasive bladder cancer is discussed separately. (See "Treatment of primary non-muscle invasive urothelial bladder cancer".)

                

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Tue Sep 01 00:00:00 GMT+00:00 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. Besaratinia A, Tommasi S. Genotoxicity of tobacco smoke-derived aromatic amines and bladder cancer: current state of knowledge and future research directions. FASEB J 2013; 27:2090.
  2. Skipper PL, Tannenbaum SR, Ross RK, Yu MC. Nonsmoking-related arylamine exposure and bladder cancer risk. Cancer Epidemiol Biomarkers Prev 2003; 12:503.
  3. Tao L, Day BW, Hu B, et al. Elevated 4-aminobiphenyl and 2,6-dimethylaniline hemoglobin adducts and increased risk of bladder cancer among lifelong nonsmokers--The Shanghai Bladder Cancer Study. Cancer Epidemiol Biomarkers Prev 2013; 22:937.
  4. Michaud DS, Spiegelman D, Clinton SK, et al. Fruit and vegetable intake and incidence of bladder cancer in a male prospective cohort. J Natl Cancer Inst 1999; 91:605.
  5. Zhou J, Smith S, Giovannucci E, Michaud DS. Reexamination of total fluid intake and bladder cancer in the Health Professionals Follow-up Study Cohort. Am J Epidemiol 2012; 175:696.
  6. Steinmaus CM, Nuñez S, Smith AH. Diet and bladder cancer: a meta-analysis of six dietary variables. Am J Epidemiol 2000; 151:693.
  7. 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; 17:1214.
  8. Yuan JM, Chan KK, Coetzee GA, et al. Genetic determinants in the metabolism of bladder carcinogens in relation to risk of bladder cancer. Carcinogenesis 2008; 29:1386.
  9. Clapp RW, Jacobs MM, Loechler EL. Environmental and occupational causes of cancer: new evidence 2005-2007. Rev Environ Health 2008; 23:1.
  10. Vickers AJ, Bennette C, Kibel AS, et al. Who should be included in a clinical trial of screening for bladder cancer?: a decision analysis of data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Cancer 2013; 119:143.
  11. Mir MC, Stephenson AJ, Grubb RL 3rd, et al. Predicting risk of bladder cancer using clinical and demographic information from prostate, lung, colorectal, and ovarian cancer screening trial participants. Cancer Epidemiol Biomarkers Prev 2013; 22:2241.
  12. Lotan R, Clifford JL. Nuclear receptors for retinoids: mediators of retinoid effects on normal and malignant cells. Biomed Pharmacother 1991; 45:145.
  13. Cohen SM, Wittenberg JF, Bryan GT. Effect of avitaminosis A and hypervitaminosis A on urinary bladder carcinogenicity of N-(4-(5-Nitro-2-furyl)-2-thiazolyl)formamide. Cancer Res 1976; 36:2334.
  14. Sporn MB, Squire RA, Brown CC, et al. 13-cis-retinoic acid: inhibition of bladder carcinogenesis in the rat. Science 1977; 195:487.
  15. Becci PJ, Thompson HJ, Grubbs CJ, et al. Inhibitory effect of 13-cis-retinoic acid on urinary bladder carcinogenesis induced in C57BL/6 mice by N-butyl-N-(4-hydroxybutyl)-nitrosamine. Cancer Res 1978; 38:4463.
  16. Mathews-Roth MM, Lausen N, Drouin G, et al. Effects of carotenoid administration on bladder cancer prevention. Oncology 1991; 48:177.
  17. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med 1994; 330:1029.
  18. Virtamo J, Edwards BK, Virtanen M, et al. Effects of supplemental alpha-tocopherol and beta-carotene on urinary tract cancer: incidence and mortality in a controlled trial (Finland). Cancer Causes Control 2000; 11:933.
  19. Alfthan O, Tarkkanen J, Gröhn P, et al. Tigason (etretinate) in prevention of recurrence of superficial bladder tumors. A double-blind clinical trial. Eur Urol 1983; 9:6.
  20. Studer UE, Jenzer S, Biedermann C, et al. Adjuvant treatment with a vitamin A analogue (etretinate) after transurethral resection of superficial bladder tumors. Final analysis of a prospective, randomized multicenter trial in Switzerland. Eur Urol 1995; 28:284.
  21. Sabichi AL, Lerner SP, Atkinson EN, et al. Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer. Clin Cancer Res 2008; 14:224.
  22. Decensi A, Torrisi R, Bruno S, et al. Randomized trial of fenretinide in superficial bladder cancer using DNA flow cytometry as an intermediate end point. Cancer Epidemiol Biomarkers Prev 2000; 9:1071.
  23. Yoshida O, Brown RR, Bryan GT. Relationship between tryptophan metabolism and heterotopic recurrences of human urinary bladder tumors. Cancer 1970; 25:773.
  24. Byar D, Blackard C. Comparisons of placebo, pyridoxine, and topical thiotepa in preventing recurrence of stage I bladder cancer. Urology 1977; 10:556.
  25. Newling DW, Robinson MR, Smith PH, et al. Tryptophan metabolites, pyridoxine (vitamin B6) and their influence on the recurrence rate of superficial bladder cancer. Results of a prospective, randomised phase III study performed by the EORTC GU Group. EORTC Genito-Urinary Tract Cancer Cooperative Group. Eur Urol 1995; 27:110.
  26. Fukushima S, Imaida K, Sakata T, et al. Promoting effects of sodium L-ascorbate on two-stage urinary bladder carcinogenesis in rats. Cancer Res 1983; 43:4454.
  27. Shibata A, Paganini-Hill A, Ross RK, Henderson BE. Intake of vegetables, fruits, beta-carotene, vitamin C and vitamin supplements and cancer incidence among the elderly: a prospective study. Br J Cancer 1992; 66:673.
  28. Nomura AM, Kolonel LN, Hankin JH, Yoshizawa CN. Dietary factors in cancer of the lower urinary tract. Int J Cancer 1991; 48:199.
  29. Bruemmer B, White E, Vaughan TL, Cheney CL. Nutrient intake in relation to bladder cancer among middle-aged men and women. Am J Epidemiol 1996; 144:485.
  30. Jacobs EJ, Henion AK, Briggs PJ, et al. Vitamin C and vitamin E supplement use and bladder cancer mortality in a large cohort of US men and women. Am J Epidemiol 2002; 156:1002.
  31. Michaud DS, Pietinen P, Taylor PR, et al. Intakes of fruits and vegetables, carotenoids and vitamins A, E, C in relation to the risk of bladder cancer in the ATBC cohort study. Br J Cancer 2002; 87:960.
  32. Liang D, Lin J, Grossman HB, et al. Plasma vitamins E and A and risk of bladder cancer: a case-control analysis. Cancer Causes Control 2008; 19:981.
  33. Michaud DS, Spiegelman D, Clinton SK, et al. Prospective study of dietary supplements, macronutrients, micronutrients, and risk of bladder cancer in US men. Am J Epidemiol 2000; 152:1145.
  34. Lotan Y, Goodman PJ, Youssef RF, et al. Evaluation of vitamin E and selenium supplementation for the prevention of bladder cancer in SWOG coordinated SELECT. J Urol 2012; 187:2005.
  35. Lamm DL, Riggs DR, Shriver JS, et al. Megadose vitamins in bladder cancer: a double-blind clinical trial. J Urol 1994; 151:21.
  36. Nepple KG, Lightfoot AJ, Rosevear HM, et al. Bacillus Calmette-Guérin with or without interferon α-2b and megadose versus recommended daily allowance vitamins during induction and maintenance intravesical treatment of nonmuscle invasive bladder cancer. J Urol 2010; 184:1915.
  37. Zeegers MP, Goldbohm RA, Bode P, van den Brandt PA. Prediagnostic toenail selenium and risk of bladder cancer. Cancer Epidemiol Biomarkers Prev 2002; 11:1292.
  38. Kellen E, Zeegers M, Buntinx F. Selenium is inversely associated with bladder cancer risk: a report from the Belgian case-control study on bladder cancer. Int J Urol 2006; 13:1180.
  39. Yalçin O, Karataş F, Erulaş FA, Ozdemir E. The levels of glutathione peroxidase, vitamin A, E, C and lipid peroxidation in patients with transitional cell carcinoma of the bladder. BJU Int 2004; 93:863.
  40. Goossens ME, Buntinx F, Joniau S, et al. Designing the selenium and bladder cancer trial (SELEBLAT), a phase lll randomized chemoprevention study with selenium on recurrence of bladder cancer in Belgium. BMC Urol 2012; 12:8.
  41. Garland M, Morris JS, Stampfer MJ, et al. Prospective study of toenail selenium levels and cancer among women. J Natl Cancer Inst 1995; 87:497.
  42. Messing EM, Hanson P, Reznikoff CA. Normal and malignant human urothelium: in vitro response to blockade of polyamine synthesis and interconversion. Cancer Res 1988; 48:357.
  43. Messing E, Kim KM, Sharkey F, et al. Randomized prospective phase III trial of difluoromethylornithine vs placebo in preventing recurrence of completely resected low risk superficial bladder cancer. J Urol 2006; 176:500.
  44. Dovedi SJ, Kirby JA, Davies BR, et al. Celecoxib has potent antitumour effects as a single agent and in combination with BCG immunotherapy in a model of urothelial cell carcinoma. Eur Urol 2008; 54:621.
  45. Sabichi AL, Lee JJ, Grossman HB, et al. A randomized controlled trial of celecoxib to prevent recurrence of nonmuscle-invasive bladder cancer. Cancer Prev Res (Phila) 2011; 4:1580.
  46. Kelly JD, Hall E. Boxing bladder cancer with COX-2-specific inhibition. Cancer Prev Res (Phila) 2011; 4:1534.
  47. Messina M, Barnes S. The role of soy products in reducing risk of cancer. J Natl Cancer Inst 1991; 83:541.
  48. Theodorescu D, Laderoute KR, Calaoagan JM, Guilding KM. Inhibition of human bladder cancer cell motility by genistein is dependent on epidermal growth factor receptor but not p21ras gene expression. Int J Cancer 1998; 78:775.
  49. Sun CL, Yuan JM, Wang XL, et al. Dietary soy and increased risk of bladder cancer: a prospective cohort study of men in Shanghai, China. Int J Cancer 2004; 112:319.
  50. Sato D, Matsushima M. Preventive effects of urinary bladder tumors induced by N-butyl-N-(4-hydroxybutyl)-nitrosamine in rat by green tea leaves. Int J Urol 2003; 10:160.
  51. Wang X, Lin YW, Wang S, et al. A meta-analysis of tea consumption and the risk of bladder cancer. Urol Int 2013; 90:10.
  52. Zhang XL, Geng J, Zhang XP, et al. Statin use and risk of bladder cancer: a meta-analysis. Cancer Causes Control 2013; 24:769.
  53. Jacobs EJ, Newton CC, Thun MJ, Gapstur SM. Long-term use of cholesterol-lowering drugs and cancer incidence in a large United States cohort. Cancer Res 2011; 71:1763.
  54. Crivelli JJ, Xylinas E, Kluth LA, et al. Effect of statin use on outcomes of non-muscle-invasive bladder cancer. BJU Int 2013; 112:E4.