Bladder Cancer: Diagnosis and Treatment

 

Am Fam Physician. 2017 Oct 15;96(8):507-514.

  Patient information: See related handout on bladder cancer.

Author disclosure: No relevant financial affiliations.

Bladder cancer is the sixth most prevalent malignancy in the United States and causes more than 16,000 deaths annually. The most common clinical presentation is asymptomatic hematuria, which should prompt evaluation with cystoscopy, renal function testing, and upper urinary tract imaging in adults 35 years and older and in those with irritative voiding symptoms, risk factors for bladder cancer, or gross hematuria at any age. Transurethral resection of the bladder tumor allows for definitive diagnosis, staging, and primary treatment. Non–muscle-invasive disease is treated with transurethral resection, most often followed by intravesical bacille Calmette-Guérin or intravesical chemotherapy. Bladder cancer that invades the muscle layer is typically treated with radical cystectomy and neoadjuvant chemotherapy because of higher rates of progression and recurrence. No major organization recommends screening asymptomatic adults for bladder cancer, and the U.S. Preventive Services Task Force concluded that current evidence is insufficient to assess the balance of benefits and harms of screening.

Bladder cancer comprises 5% of new cancer diagnoses in the United States and is the sixth most prevalent malignancy.1 About 90% of affected patients are older than 55 years, with a mean age at diagnosis of 73 years.1 Men are three to four times more likely than women to develop the disease, with a lifetime risk of one in 26 for men and one in 88 for women.1 Bladder cancer affects whites about two times more often than blacks or Hispanics, but it is more likely to be diagnosed at an advanced stage in black patients.1 As the incidence of the disease has decreased, bladder cancer–related mortality has decreased for women but remains unchanged for men.1 An estimated 16,400 deaths were caused by bladder cancer in 2016.1

 Enlarge     Print

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferencesComments

Urine cytology and testing for urine tumor markers should not be performed routinely for evaluation of bladder cancer.

C

21, 29

Urine cytology has > 90% sensitivity for detection of high-grade tumors and carcinoma in situ; it can be of benefit in patients with high pretest probability of disease.

Cystoscopy should be performed in all patients with gross hematuria, all patients 35 years and older who have microscopic hematuria, and all patients with symptomatic microscopic hematuria of unclear etiology, regardless of age.

C

21

Initial evaluation for bladder cancer should include imaging of the upper urinary tract.

C

27, 30

Computed tomography urography is preferred.

Non–muscle-invasive bladder cancer should be treated with transurethral resection of the tumor, with or without intravesical instillation of immunotherapy or chemotherapy.

C

20, 27, 32

Cisplatin-based neoadjuvant chemotherapy should be considered in addition to radical cystectomy with extended lymphadenectomy for additional survival benefit in patients with muscle-invasive bladder cancer.

A

29

There is an absolute five-year survival benefit of 5% to 8%.

The U.S. Preventive Services Task Force concludes the current evidence is insufficient to assess the balance of benefits and harms of screening for bladder cancer in asymptomatic adults.

C

33

The American Academy of Family Physicians concurs.


A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort.

SORT: KEY RECOMMENDATIONS FOR PRACTICE

Clinical recommendationEvidence ratingReferencesComments

Urine cytology and testing for urine tumor markers should not be performed routinely for evaluation of bladder cancer.

C

21, 29

Urine cytology has > 90% sensitivity for detection of high-grade tumors and carcinoma in situ; it can be of benefit in patients with high pretest probability of disease.

Cystoscopy should be performed in all patients with gross hematuria, all patients 35 years and older who have microscopic hematuria, and all patients with symptomatic microscopic hematuria of unclear etiology, regardless of age.

C

21

Initial evaluation for bladder cancer should include imaging of the upper urinary tract.

C

27, 30

Computed tomography urography is preferred.

Non–muscle-invasive bladder cancer should be treated with transurethral resection of the tumor, with or without intravesical instillation of immunotherapy or chemotherapy.

C

20, 27, 32

Cisplatin-based neoadjuvant chemotherapy should be considered in addition to radical cystectomy with extended lymphadenectomy for additional survival benefit in patients with muscle-invasive bladder cancer.

A

29

There is an absolute five-year survival benefit of 5% to 8%.

The U.S. Preventive Services Task Force concludes the current evidence is insufficient

The Authors

show all author info

KATHARINE C. DeGEORGE, MD, MS, is an assistant professor of family medicine at the University of Virginia School of Medicine, Charlottesville....

HARRY R. HOLT, MD, is a family physician at Baltimore (Md.) Medical System. At the time this article was written, he was an assistant professor of family medicine at the University of Virginia School of Medicine.

STEPHANIE C. HODGES, MD, is a family physician at the Everett Clinic, Lake Stevens, Wash. At the time this artcile was written, she was a third-year family medicine resident at the University of Virginia School of Medicine.

Address correspondence to Katharine C. DeGeorge, MD, MS, University of Virginia, P.O. Box 800729, Charlottesville, VA 22908 (e-mail: kd6fp@mcc.virginia.edu). Reprints are not available from the authors.

Author disclosure: No relevant financial affiliations.


This article updates a previous article on this topic by Sharma, et al.35

Data Sources: A PubMed search was completed in Clinical Queries using the key terms bladder cancer, diagnosis, treatment, hematuria, urothelial mass, bladder carcinoma, carcinoma in situ, and transurethral resection of bladder tumor. The search included meta-analyses, randomized controlled trials, clinical trials, and reviews. We also searched DynaMed Plus, the Agency for Healthcare Research and Quality evidence reports, Clinical Evidence, the Cochrane database, Essential Evidence Plus, the National Comprehensive Cancer Network, and the National Guideline Clearinghouse database. Search dates: May 20, 2016, and April 28, 2017.

REFERENCES

show all references

1. American Cancer Society. Key statistics for bladder cancer. http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-key-statistics. Accessed May 20, 2016....

2. American Cancer Society. Bladder cancer risk factors. http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-risk-factors. Accessed May 20, 2016.

3. Freedman ND, Silverman DT, Hollenbeck AR, Schatzkin A, Abnet CC. Association between smoking and risk of bladder cancer among men and women [published correction appears in JAMA. 2011;306(20): 2220]. JAMA. 2011;306(7):737–745.

4. Ferrucci LM, Sinha R, Ward MH, et al. Meat and components of meat and the risk of bladder cancer in the NIH-AARP Diet and Health Study. Cancer. 2010;116(18):4345–4353.

5. American Cancer Society. Can bladder cancer be found early? http://www.cancer.org/cancer/bladdercancer/detailedguide/bladder-cancer-detection. Accessed May 20, 2016.

6. Ho CH, Sung KC, Lim SW, et al. Chronic indwelling urinary catheter increase the risk of bladder cancer, even in patients without spinal cord injury. Medicine (Baltimore). 2015;94(43):e1736.

7. Mostafa MH, Sheweita SA, O'Connor PJ. Relationship between schistosomiasis and bladder cancer. Clin Microbiol Rev. 1999;12(1):97–111.

8. Sun JW, Zhao LG, Yang Y, Ma X, Wang YY, Xiang YB. Obesity and risk of bladder cancer: a dose-response meta-analysis of 15 cohort studies. PLoS One. 2015;10(3):e0119313.

9. Mathews JD, Forsythe AV, Brady Z, et al. Cancer risk in 680,000 people exposed to computed tomography scans in childhood or adolescence: data linkage study of 11 million Australians. BMJ. 2013;346:f2360.

10. Yan L, Chen P, Chen EZ, Gu A, Jiang ZY. Risk of bladder cancer in renal transplant recipients: a meta-analysis. Br J Cancer. 2014;110(7):1871–1877.

11. Guillaume L, Guy L. Epidemiology of and risk factors for bladder cancer and for urothelial tumors (in French). Rev Prat. 2014;64(10):1372–1374, 1378–1380.

12. Janković S, Radosavljević V. Risk factors for bladder cancer. Tumori. 2007;93(1):4–12.

13. Ferwana M, Firwana B, Hasan R, et al. Pioglitazone and risk of bladder cancer: a meta-analysis of controlled studies. Diabet Med. 2013;30(9):1026–1032.

14. Zhu Z, Wang X, Shen Z, Lu Y, Zhong S, Xu C. Risk of bladder cancer in patients with diabetes mellitus: an updated meta-analysis of 36 observational studies. BMC Cancer. 2013;13:310.

15. Li N, Yang L, Zhang Y, Zhao P, Zheng T, Dai M. Human papillomavirus infection and bladder cancer risk: a meta-analysis. J Infect Dis. 2011;204(2):217–223.

16. Olfert SM, Felknor SA, Delclos GL. An updated review of the literature: risk factors for bladder cancer with focus on occupational exposures. South Med J. 2006;99(11):1256–1263.

17. Bellmunt J, Orsola A, Leow JJ, Wiegel T, De Santis M, Horwich A; ESMO Guidelines Working Group. Bladder cancer: ESMO practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014;25(suppl 3): iii40–iii48.

18. Grignon DJ. The current classification of urothelial neoplasms. Mod Pathol. 2009;22(suppl 2):S60–S69.

19. Badawi AF, Mostafa MH, Probert A, O'Connor PJ. Role of schistosomiasis in human bladder cancer: evidence of association, aetiological factors, and basic mechanisms of carcinogenesis. Eur J Cancer Prev. 1995;4(1):45–59.

20. Hall MC, Chang SS, Dalbagni G, et al. Guideline for the management of nonmuscle invasive bladder cancer (stages Ta, T1, and Tis): 2007 update. J Urol. 2007;178(6):2314–2330.

21. Davis R, Jones JS, Barocas DA, et al.; American Urological Association. Diagnosis, evaluation and follow-up of asymptomatic microhematuria (AMH) in adults: AUA guideline. J Urol. 2012;188(6 suppl):2473–2481.

22. Pashos CL, Botteman MF, Laskin BL, Redaelli A. Bladder cancer: epidemiology, diagnosis, and management. Cancer Pract. 2002;10(6): 311–322.

23. Mohr DN, Offord KP, Owen RA, Melton LJ III. Asymptomatic microhematuria and urologic disease. A population-based study. JAMA. 1986;256(2):224–229.

24. Golin AL, Howard RS. Asymptomatic microscopic hematuria. J Urol. 1980;124(3):389–391.

25. American Cancer Society. Cancer facts and figures 2016. http://www.cancer.org/acs/groups/content/@research/documents/document/acspc-047079.pdf. Accessed May 20, 2016.

26. Shinagare AB, Ramaiya NH, Jagannathan JP, Fennessy FM, Taplin ME, Van den Abbeele AD. Metastatic pattern of bladder cancer: correlation with the characteristics of the primary tumor. AJR Am J Roentgenol. 2011;196(1):117–122.

27. Clark PE, Agarwal N, Biagioli MC, et al.; National Comprehensive Cancer Network. Bladder cancer. J Natl Compr Canc Netw. 2013;11(4):446–475.

28. Sharp VJ, Barnes KT, Erickson BA. Assessment of asymptomatic microscopic hematuria in adults. Am Fam Physician. 2013;88(11):747–754.

29. Witjes JA, Compérat E, Cowan NC, et al.; European Association of Urology. EAU guidelines on muscle-invasive and metastatic bladder cancer: summary of the 2013 guidelines. Eur Urol. 2014;65(4):778–792.

30. American College of Radiology. ACR appropriateness criteria: hematuria. https://acsearch.acr.org/docs/69490/Narrative. Accessed May 20, 2016.

31. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A III. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer; 2010:573–574.

32. Babjuk M, Böhle A, Burger M, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2016. Eur Urol. 2017;71(3):447–461.

33. Moyer VA; U.S. Preventive Services Task Force. Screening for bladder cancer: U.S. Preventive Services Task Force recommendation statement [published correction appears in Ann Intern Med. 2011;155(6):408.] Ann Intern Med. 2011;155(4):246–251.

34. American Academy of Family Physicians. Clinical preventive service recommendation: bladder cancer. http://www.aafp.org/patient-care/clinical-recommendations/all/bladder-cancer.html. Accessed May 20, 2016.

35. Sharma S, Ksheersagar P, Sharma P. Diagnosis and treatment of bladder cancer. Am Fam Physician. 2009;80(7):717–723.

36. Chang SS, Bochner BH, Chou R, et al. Treatment of non-metastatic muscle-invasive bladder cancer: AUA/ASCO/ASTRO/SUO guideline. J Urol. Published online ahead of print April 26, 2017. http://www.sciencedirect.com/science/article/pii/S0022534717578362. Accessed June 6, 2017.

37. Aldousari S, Kassouf W. Update on the management of non-muscle invasive bladder cancer. Can Urol Assoc J. 2010;4(1):56–64.

38. Chang SS, Boorjian SA, Chou R, et al. Diagnosis and treatment of non-muscle invasive bladder cancer: AUA/SUO guideline. J Urol. 2016;196(4):1021–1029.

39. Sfakianos JP, Kim PH, Hakimi AA, Herr HW. The effect of restaging transurethral resection on recurrence and progression rates in patients with nonmuscle invasive bladder cancer treated with intravesical bacillus Calmette-Guérin. J Urol. 2014;191(2):341–345.

40. Hollenbeck BK, Dunn RL, Ye Z, et al. Delays in diagnosis and bladder cancer mortality. Cancer. 2010;116(22):5235–5242.

41. Gore JL, Lai J, Setodji CM, Litwin MS, Saigal CS; Urologic Diseases in America Project. Mortality increases when radical cystectomy is delayed more than 12 weeks: results from a surveillance, epidemiology, and end results-Medicare analysis. Cancer. 2009;115(5):988–996.

42. Petrelli F, Coinu A, Cabiddu M, Ghilardi M, Vavassori I, Barni S. Correlation of pathologic complete response with survival after neoadjuvant chemotherapy in bladder cancer treated with cystectomy: a meta-analysis. Eur Urol. 2014;65(2):350–357.

43. Grossman HB, Natale RB, Tangen CM, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer [published ocrrection appears in N Engl J Med. 2003; 349(19):1880]. N Engl J Med. 2003;349(9):859–866.

44. Griffiths G, Hall R, Sylvester R, Raghavan D, Parmar MK; International Collaboration of Trialists; Medical Research Council Advanced Bladder Cancer Working Party (now the National Cancer Research Institute Bladder Cancer Clinical Studies Group); European Organisation for Research and Treatment of Cancer Genito-Urinary Tract Cancer Group; Australian Bladder Cancer Study Group; National Cancer Institute of Canada Clinical Trials Group; Finnbladder; Norwegian Bladder Cancer Study Group; Club Urologico Espanol de Tratamiento Oncologico Group. International phase III trial assessing neoadjuvant cisplatin, methotrexate, and vinblastine chemotherapy for muscle-invasive bladder cancer: long-term results of the BA06 30894 trial. J Clin Oncol. 2011;29(16): 2171–2177.

45. Stimson CJ, Chang SS, Barocas DA, et al. Early and late perioperative outcomes following radical cystectomy: 90-day readmissions, morbidity and mortality in a contemporary series. J Urol. 2010;184(4):1296–1300.

46. Bochner BH, Dalbagni G, Sjoberg DD, et al. Comparing open radical cystectomy and robot-assisted laparoscopic radical cystectomy: a randomized clinical trial. Eur Urol. 2015;67(6):1042–1050.

47. Yuh B, Wilson T, Bochner B, et al. Systematic review and cumulative analysis of oncologic and functional outcomes after robot-assisted radical cystectomy. Eur Urol. 2015;67(3):402–422.

48. Shelley MD, Barber J, Wilt T, Mason MD. Surgery versus radiotherapy for muscle invasive bladder cancer. Cochrane Database Syst Rev. 2002;(1): CD002079.

49. Cody JD, Nabi G, Dublin N, et al. Urinary diversion and bladder reconstruction/replacement using intestinal segments for intractable incontinence or following cystectomy. Cochrane Database Syst Rev. 2012;(2): CD003306.

50. Fedeli U, Fedewa SA, Ward EM. Treatment of muscle invasive bladder cancer: evidence from the National Cancer Database, 2003 to 2007. J Urol. 2011;185(1):72–78.

51. Ruggeri EM, Fabbri MA, Nelli F. Should we use adjuvant chemotherapy for muscle-invasive bladder cancer after radical cystectomy? J Clin Oncol. 2016;34(26):3223.

52. Advanced Bladder Cancer Overview Collaboration. Neoadjuvant chemotherapy for invasive bladder cancer. Cochrane Database Syst Rev. 2005;(2):CD005246.

53. Leow JJ, Martin-Doyle W, Rajagopal PS, et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol. 2014;66(1):42–54.

54. Shelley M, Cleves A, Wilt TJ, Mason M. Gemcitabine for unresectable, locally advanced or metastatic bladder cancer. Cochrane Database Syst Rev. 2011;(4):CD008976.

55. Shelley MD, Cleves A, Wilt TJ, Mason MD. Gemcitabine chemotherapy for the treatment of metastatic bladder carcinoma. BJU Int. 2011; 108(2):168–179.

56. National Cancer Institute. Cancer stat facts: bladder cancer. http://seer.cancer.gov/statfacts/html/urinb.html. Accessed May 27, 2016.

 

 

Copyright © 2017 by the American Academy of Family Physicians.
This content is owned by the AAFP. A person viewing it online may make one printout of the material and may use that printout only for his or her personal, non-commercial reference. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. Contact afpserv@aafp.org for copyright questions and/or permission requests.

Want to use this article elsewhere? Get Permissions

CME Quiz

More in AFP


Editor's Collections


Related Content


Email Alerts

Don't miss a single issue. Sign up for the free AFP email table of contents.

Sign Up Now

Navigate this Article