World Journal of Urology

, Volume 29, Issue 4, pp 457–463 | Cite as

Impact of gender on bladder cancer incidence, staging, and prognosis

  • Harun Fajkovic
  • Joshua A. Halpern
  • Eugene K. Cha
  • Atessa Bahadori
  • Thomas F. Chromecki
  • Pierre I. Karakiewicz
  • Eckart Breinl
  • Axel S Merseburger
  • Shahrokh F. Shariat
Topic Paper



While patient gender is an important factor in the clinical decision-making for the management of bladder cancer, there are minimal evidence-based recommendations to guide health care professionals. Recent epidemiologic and translational research has shed some light on the complex relationship between gender and bladder cancer. Our aim was to review the literature on the effect of gender on bladder cancer incidence, biology, mortality, and treatment.


Using MEDLINE, we performed a search of the literature between January 1975 and April 2011.


Although men are nearly 3–4 times more likely to develop bladder cancer than women, women present with more advanced disease and have worse survival. Recently, a number of population-based and multicenter collaborative studies have shown that female gender is associated with a significantly higher rate of cancer-specific recurrence and mortality after radical cystectomy. The disparity between genders is proposed to be the result of a differences exposure to carcinogens (i.e., tobacco and chemicals) as well as reflective of genetic, anatomic, hormonal, societal, and environmental factors. Explanations for the differential behavior of bladder cancer between genders include sex steroids and their receptors as well as inferior quality of care for women (inpatient length of stay, referral patterns, and surgical outcomes).


It is imperative that health care practitioners and researchers from disparate disciplines collectively focus efforts to appropriately develop gender-specific evidence-based guidelines for bladder cancer patients. We must strive to develop multidisciplinary collaborative efforts to provide tailored gender-specific care for bladder cancer patients.


Female Male Gender Recurrence Survival Bladder cancer prognosis Urothelial carcinoma 


Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics. CA Cancer J Clin 60:277–300PubMedCrossRefGoogle Scholar
  2. 2.
    Sievert KD, Amend B, Nagele U et al (2009) Economic aspects of bladder cancer: what are the benefits and costs? World J Urol 27:295–300PubMedCrossRefGoogle Scholar
  3. 3.
    Herman MP, Svatek RS, Lotan Y, Karakiewizc PI, Shariat SF (2008) Urine-based biomarkers for the early detection and surveillance of non-muscle invasive bladder cancer. Minerva Urol Nefrol 60:217–235PubMedGoogle Scholar
  4. 4.
    Shariat SF, Karakiewicz PI, Palapattu GS, et al (2006) Outcomes of radical cystectomy for transitional cell carcinoma of the bladder: a contemporary series from the Bladder Cancer Research Consortium. J Urol 176:2414–22 (discussion 22)Google Scholar
  5. 5.
    Stein JP, Lieskovsky G, Cote R et al (2001) Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1, 054 patients. J Clin Oncol 19:666–675PubMedGoogle Scholar
  6. 6.
    Madersbacher S, Hochreiter W, Burkhard F et al (2003) Radical cystectomy for bladder cancer today–a homogeneous series without neoadjuvant therapy. J Clin Oncol 21:690–696PubMedCrossRefGoogle Scholar
  7. 7.
    USIo Medicine (2001) Exploring the biological contributions to human health: does sex matter? J Womens Health Gend Based Med 10:433–439CrossRefGoogle Scholar
  8. 8.
    Pushkar DY, Govorov AV, Matveev VB (2008) The epidemiology of bladder cancer in Russia. Scand J Urol Nephrol Suppl 218:21–24Google Scholar
  9. 9.
    Puente D, Malats N, Cecchini L et al (2003) Gender-related differences in clinical and pathological characteristics and therapy of bladder cancer. Eur Urol 43:53–62PubMedCrossRefGoogle Scholar
  10. 10.
    Horstmann M, Witthuhn R, Falk M, Stenzl A (2008) Gender-specific differences in bladder cancer: a retrospective analysis. Gend Med 5:385–394PubMedCrossRefGoogle Scholar
  11. 11.
    Mungan NA, Aben KK, Schoenberg MP et al (2000) Gender differences in stage-adjusted bladder cancer survival. Urology 55:876–880PubMedCrossRefGoogle Scholar
  12. 12.
    Mungan NA, Kiemeney LA, van Dijck JA, van der Poel HG, Witjes JA (2000) Gender differences in stage distribution of bladder cancer. Urology 55:368–371PubMedCrossRefGoogle Scholar
  13. 13.
    Pou SA, Osella AR, Diaz MeP (2011) Bladder cancer mortality trends and patterns in Córdoba, Argentina (1986–2006). Cancer Causes Control 22:407–415PubMedCrossRefGoogle Scholar
  14. 14.
    Tracey E, Roder D, Luke C, Bishop J (2009) Bladder cancer survivals in New South Wales, Australia: why do women have poorer survival than men? BJU Int 104:498–504PubMedCrossRefGoogle Scholar
  15. 15.
    Svatek RS, Shariat SF, Dinney C et al (2009) Evidence-based gender related outcomes after radical cystectomy: results of a large multicenter study (abstract #1744). J Urol 181:629CrossRefGoogle Scholar
  16. 16.
    Jeldres C, Isbarn H, Capitanio U et al (2009) Gender is an important predictor of cancer-specific survival in patients with urothelial carcinoma after radical cystectomy (abstract #1761). J Urol 181:635CrossRefGoogle Scholar
  17. 17.
    Datta GD, Neville B, Datta NS, Earle C (2006) Gender disparities in bladder cancer survival: An assessment of socio-demographic factors. AACR Meeting Abstracts. 2006:B38 (2006 November 1)Google Scholar
  18. 18.
    Scosyrev E, Noyes K, Feng C, Messing E (2009) Sex and racial differences in bladder cancer presentation and mortality in the US. Cancer 115:68–74PubMedCrossRefGoogle Scholar
  19. 19.
    Tilki D, Reich O, Svatek RS et al (2010) Characteristics and outcomes of patients with clinical carcinoma in situ only treated with radical cystectomy: an international study of 243 patients. J Urol 183:1757–1763PubMedCrossRefGoogle Scholar
  20. 20.
    Tilki D, Svatek RS, Novara G et al (2010) Stage pT0 at radical cystectomy confers improved survival: an international study of 4, 430 patients. J Urol 184:888–894PubMedCrossRefGoogle Scholar
  21. 21.
    Tilki D, Svatek RS, Karakiewicz PI et al (2010) Characteristics and outcomes of patients with pT4 urothelial carcinoma at radical cystectomy: a retrospective international study of 583 patients. J Urol 183:87–93PubMedCrossRefGoogle Scholar
  22. 22.
    Liberman D, Alasker A, Sun M et al (2011) Radical cystectomy for patients with pT4 urothelial carcinoma in a large population-based study. BJU Int 107:905–911PubMedCrossRefGoogle Scholar
  23. 23.
    Yafi FA, Duclos M, Correa JA, Tanguay S, Aprikian AG, Cury F, Souhami L, Rajan R, Kassouf W (2011) Contemporary outcome and management of patients who had an aborted cystectomy due to unresectable bladder cancer. Urol Oncol 29(3):309–313Google Scholar
  24. 24.
    Brookfield KF, Cheung MC, Gomez C et al (2009) Survival disparities among African American women with invasive bladder cancer in Florida. Cancer 115:4196–4209PubMedCrossRefGoogle Scholar
  25. 25.
    Lloyd-Jones D, Adams RJ, Brown TM et al (2010) Heart disease and stroke statistics–2010 update: a report from the American Heart Association. Circulation 121:e46–e215PubMedCrossRefGoogle Scholar
  26. 26.
    Hemelt M, Yamamoto H, Cheng KK, Zeegers MP (2009) The effect of smoking on the male excess of bladder cancer: a meta-analysis and geographical analyses. Int J Cancer 124:412–419PubMedCrossRefGoogle Scholar
  27. 27.
    Hartge P, Harvey EB, Linehan WM et al (1990) Unexplained excess risk of bladder cancer in men. J Natl Cancer Inst 82:1636–1640PubMedCrossRefGoogle Scholar
  28. 28.
    McGrath M, Michaud DS, De Vivo I (2006) Hormonal and reproductive factors and the risk of bladder cancer in women. Am J Epidemiol 163:236–244PubMedCrossRefGoogle Scholar
  29. 29.
    Okajima E, Hiramatsu T, Iriya K, Ijuin M, Matsushima S (1975) Effects of sex hormones on development of urinary bladder tumours in rats induced by N-butyl-N-(4-hydroxybutyl) nitrosamine. Urol Res 3:73–79PubMedCrossRefGoogle Scholar
  30. 30.
    Miyamoto H, Yang Z, Chen YT et al (2007) Promotion of bladder cancer development and progression by androgen receptor signals. J Natl Cancer Inst 99:558–568PubMedCrossRefGoogle Scholar
  31. 31.
    Boorman GA (1977) Animal model of human disease: carcinoma of the ureter and urinary bladder. Am J Pathol 88:251–254PubMedGoogle Scholar
  32. 32.
    Imada S, Akaza H, Ami Y, Koiso K, Ideyama Y, Takenaka T (1997) Promoting effects and mechanisms of action of androgen in bladder carcinogenesis in male rats. Eur Urol 31:360–364PubMedGoogle Scholar
  33. 33.
    Zhuang YH, Blauer M, Tammela T, Tuohimaa P (1997) Immunodetection of androgen receptor in human urinary bladder cancer. Histopathology 30:556–562PubMedCrossRefGoogle Scholar
  34. 34.
    Boorjian S, Ugras S, Mongan NP et al (2004) Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64:383–388PubMedCrossRefGoogle Scholar
  35. 35.
    Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND, van der Kwast TH (1991) Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem 39:927–936PubMedCrossRefGoogle Scholar
  36. 36.
    Chen F, Langenstroer P, Zhang G, Iwamoto Y, See WA (2003) Androgen dependent regulation of bacillus Calmette-Guerin induced interleukin-6 expression in human transitional carcinoma cell lines. J Urol 170:2009–2013PubMedCrossRefGoogle Scholar
  37. 37.
    Boorjian S, Ugras S, Mongan NP et al (2004) Androgen receptor expression is inversely correlated with pathologic tumor stage in bladder cancer. Urology 64:383–388PubMedCrossRefGoogle Scholar
  38. 38.
    Tuygun C, Kankaya D, Imamoglu A et al (2011) Sex-specific hormone receptors in urothelial carcinomas of the human urinary bladder: a comparative analysis of clinicopathological features and survival outcomes according to receptor expression. Urol Oncol 29:43–51PubMedCrossRefGoogle Scholar
  39. 39.
    Mir C, Shariat SF, Van Der Kwast TH et al (2010) Loss of androgen receptor expression is not associated with pathological stage, grade, gender or outcome in bladder cancer: a large multi-institutional study. BJU Int. doi: 10.1111/j.1464-410X.2010.09834.x
  40. 40.
    Shen SS, Smith CL, Hsieh JT et al (2006) Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer 106:2610–2616PubMedCrossRefGoogle Scholar
  41. 41.
    Bolenz C, Lotan Y, Ashfaq R, Shariat SF (2009) Estrogen and progesterone hormonal receptor expression in urothelial carcinoma of the bladder. Eur Urol 56:1093–1095PubMedCrossRefGoogle Scholar
  42. 42.
    Sonpavde G, Okuno N, Weiss H et al (2007) Efficacy of selective estrogen receptor modulators in nude mice bearing human transitional cell carcinoma. Urology 69:1221–1226PubMedCrossRefGoogle Scholar
  43. 43.
    Pelletier G (2000) Localization of androgen and estrogen receptors in rat and primate tissues. Histol Histopathol 15:1261–1270PubMedGoogle Scholar
  44. 44.
    Makela S, Strauss L, Kuiper G et al (2000) Differential expression of estrogen receptors alpha and beta in adult rat accessory sex glands and lower urinary tract. Mol Cell Endocrinol 170:219–229PubMedCrossRefGoogle Scholar
  45. 45.
    Saez S, Martin PM (1981) Evidence of estrogen receptors in the trigone area of human urinary bladder. J Steroid Biochem 15:317–320PubMedCrossRefGoogle Scholar
  46. 46.
    Shen SS, Smith CL, Hsieh JT et al (2006) Expression of estrogen receptors-alpha and -beta in bladder cancer cell lines and human bladder tumor tissue. Cancer 106:2610–2616PubMedCrossRefGoogle Scholar
  47. 47.
    Wolpert BJ, Amr S, Saleh DA et al (2011) Associations differ by sex for catechol-O-methyltransferase genotypes and bladder cancer risk in South Egypt. Urol Oncol [Epub ahead of print]Google Scholar
  48. 48.
    Taub DA, Hollenbeck BK, Cooper KL et al (2006) Racial disparities in resource utilization for cystectomy. Urology 67:288–293PubMedCrossRefGoogle Scholar
  49. 49.
    Cárdenas-Turanzas M, Cooksley C, Kamat AM, Pettaway CA, Elting LS (2008) Gender and age differences in blood utilization and length of stay in radical cystectomy: a population-based study. Int Urol Nephrol 40:893–899PubMedCrossRefGoogle Scholar
  50. 50.
    Siegrist T, Savage C, Shabsigh A, Cronin A, Donat SM (2010) Analysis of gender differences in early perioperative complications following radical cystectomy at a tertiary cancer center using a standardized reporting methodology. Urol Oncol 28:112–117PubMedCrossRefGoogle Scholar
  51. 51.
    Liberman D, Lughezzani G, Sun M et al (2011) Perioperative mortality is significantly greater in septuagenarian and octogenarian patients treated with radical cystectomy for urothelial carcinoma of the bladder. Urology 77:660–666PubMedCrossRefGoogle Scholar
  52. 52.
    Nagele U, Anastasiadis AG, Stenzl A, Kuczyk M (2011) Radical cystectomy with orthotopic neobladder for invasive bladder cancer: a critical analysis of long-term oncological, functional, and quality of life results. World J Urol [Epub ahead of print]Google Scholar
  53. 53.
    Porter MP, Gore JL, Wright JL (2011) Hospital volume and 90-day mortality risk after radical cystectomy: a population-based cohort study. World J Urol 29:73–77PubMedCrossRefGoogle Scholar
  54. 54.
    Schulman KA, Berlin JA, Harless W et al (1999) The effect of race and sex on physicians’ recommendations for cardiac catheterization. N Engl J Med 340:618–626PubMedCrossRefGoogle Scholar
  55. 55.
    Johnson EK, Daignault S, Zhang Y, Lee CT (2008) Patterns of hematuria referral to urologists: does a gender disparity exist? Urology 72:498–502 discussion -3PubMedCrossRefGoogle Scholar
  56. 56.
    Nielsen ME, Palapattu GS, Karakiewicz PI et al (2007) A delay in radical cystectomy of >3 months is not associated with a worse clinical outcome. BJU Int 100:1015–1020PubMedGoogle Scholar
  57. 57.
    Gore JL, Lai J, Setodji CM, Litwin MS, Saigal CS (2009) Project UDiA. Mortality increases when radical cystectomy is delayed more than 12 weeks: results from a Surveillance, Epidemiology, and End Results-Medicare analysis. Cancer 115:988–996PubMedCrossRefGoogle Scholar
  58. 58.
    Mallin K, David KA, Carroll PR, Milowsky MI, Nanus DM (2011) Transitional cell carcinoma of the bladder: racial and gender disparities in survival (1993 to 2002), stage and grade (1993 to 2007). J Urol 185:1631–1636PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • Harun Fajkovic
    • 1
    • 2
  • Joshua A. Halpern
    • 1
  • Eugene K. Cha
    • 1
  • Atessa Bahadori
    • 1
  • Thomas F. Chromecki
    • 1
    • 3
  • Pierre I. Karakiewicz
    • 4
  • Eckart Breinl
    • 2
  • Axel S Merseburger
    • 5
  • Shahrokh F. Shariat
    • 1
  1. 1.Department of Urology and Division of Medical Oncology, Weill Cornell Medical CollegeNew York-Presbyterian HospitalNew YorkUSA
  2. 2.Landesklinikum St. PoeltenSankt PoeltenAustria
  3. 3.Medical University of GrazGrazAustria
  4. 4.University of MontréalMontréalCanada
  5. 5.Department of UrologyHannover Medical SchoolHannoverGermany

Personalised recommendations