Ewha Med J.  2014 Mar;37(1):1-9. 10.12771/emj.2014.37.1.1.

Current Evidence for the Treatment of Bladder Cancer

• Kim KH
• Park YY

• KMID: 2171267
• DOI: http://doi.org/10.12771/emj.2014.37.1.1

Abstract

Bladder cancer is the second most common malignancy in urological field. Most new cases are diagnosed as non-muscle invasive bladder cancer (NMIBC), which includes Ta, T1 or carcinoma in situ. Initial management of NMIBC is endoscopic resection, which allows both treatment and pathological staging. Urologist should consider adjuvant intravesical chemotherapy or Bacillus Calmette-Guerin (BCG) immunotherapy, depending on the tumor grade or stage to prevent recurrence and progression. Patients with muscle invasive bladder cancer (MIBC) are best treated with radical cystectomy. However, radical cystectomy should be considered even in patients with NMIBC with high risk of progression and BCG refractory tumors. Delay of radical cystectomy in these patients might lead decreased disease specific survival. Patients treated by radical cystectomy should undergo any form of the urinary diversion. Ileal conduit is still most common method for urinary diversion. Orthotopic neobladder is generally performed by experienced hands in high volume center. Patients undergoing orthotopic neobladder should be educated and manually skillful to manipulate their diversion. Neoadjuvant cisplatin-based chemotherapy is recommended based on level 1 evidence with survival benefit. Recent updated meta-analysis also demonstrated survival benefit in patients with MIBC treated by adjuvant chemotherapy.

Keyword

Urinary bladder neoplasms; Cystectomy; Urinary diversion

MeSH Terms

Bacillus
Carcinoma in Situ
Chemotherapy, Adjuvant
Cystectomy
Drug Therapy
Hand
Humans
Immunotherapy
Mycobacterium bovis
Recurrence
Urinary Bladder Neoplasms*
Urinary Bladder*
Urinary Diversion

Figure

• 

  Fig. 1 Non muscle invasive bladder cancer. (A) Cystoscopy reveals papillary bladder tumor (BT), located lateral to the left ureteral orfice. (B) The bladder mass (arrow) is detected in computed tomography on the left posterior wall of the urinary bladder with enhancement. BT, bladder tumor.

• 

  Fig. 2 Orthotopic neobladder formation using Studer method. (A) Ileal neobladder is consisted of afferent tubular limb and spherical reservoir. Afferent tubular limb is used for ureteral implantation and prevents ureteral reflux using bowel peristalsis. Spherical reservoir is formed by detubularization and four-cross folding of ileal segments to maximize bladder capacity and minimize intra-luminal pressure. (B) Most caudal part of the ileal neobladder is anastomosed to urethra over the urethral catheter. L, afferent tubular limb; R, spherical reservoir; N, neobladder; U, urethra.

Reference

1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008 GLOBOCAN. Int J Cancer. 2010; 127:2893–2917.

2. National Cancer Information Center. Available from: http://www.cancer.go.kr/mbs/cancer/.

3. Burger M, Catto JW, Dalbagni G, Grossman HB, Herr H, Karakiewicz P, et al. Epidemiology and risk factors of urothelial bladder cancer. Eur Urol. 2013; 63:234–241.

4. Ploeg M, Aben KK, Kiemeney LA. The present and future burden of urinary bladder cancer in the world. World J Urol. 2009; 27:289–293.

5. Zeegers MP, Tan FE, Dorant E, van Den Brandt PA. The impact of characteristics of cigarette smoking on urinary tract cancer risk: a meta-analysis of epidemiologic studies. Cancer. 2000; 89:630–639.

6. Babjuk M, Burger M, Zigeuner R, Shariat SF, van Rhijn BW, Comperat E, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol. 2013; 64:639–653.

7. Stenzl A, Cowan NC, De Santis M, Kuczyk MA, Merseburger AS, Ribal MJ, et al. Treatment of muscle-invasive and metastatic bladder cancer: update of the EAU guidelines. Eur Urol. 2011; 59:1009–1018.

8. Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010; 17:1471–1474.

9. Kirkali Z, Chan T, Manoharan M, Algaba F, Busch C, Cheng L, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology. 2005; 66:4–34.

10. Mariappan P, Zachou A, Grigor KM. Edinburgh Uro-Oncology Group. Detrusor muscle in the first, apparently complete transurethral resection of bladder tumour specimen is a surrogate marker of resection quality, predicts risk of early recurrence, and is dependent on operator experience. Eur Urol. 2010; 57:843–849.

11. Palou J, Sylvester RJ, Faba OR, Parada R, Pena JA, Algaba F, et al. Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guérin. Eur Urol. 2012; 62:118–125.

12. Kausch I, Sommerauer M, Montorsi F, Stenzl A, Jacqmin D, Jichlinski P, et al. Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urol. 2010; 57:595–606.

13. Witjes JA, Redorta JP, Jacqmin D, Sofras F, Malmström PU, Riedl C, et al. Hexaminolevulinate-guided fluorescence cystoscopy in the diagnosis and follow-up of patients with non-muscle-invasive bladder cancer: review of the evidence and recommendations. Eur Urol. 2010; 57:607–614.

14. Mowatt G, N'Dow J, Vale L, Nabi G, Boachie C, Cook JA, et al. Photodynamic diagnosis of bladder cancer compared with white light cystoscopy: systematic review and meta-analysis. Int J Technol Assess Health Care. 2011; 27:3–10.

15. Schumacher MC, Holmang S, Davidsson T, Friedrich B, Pedersen J, Wiklund NP. Transurethral resection of non-muscle-invasive bladder transitional cell cancers with or without 5-aminolevulinic Acid under visible and fluorescent light: results of a prospective, randomised, multicentre study. Eur Urol. 2010; 57:293–299.

16. Stenzl A, Penkoff H, Dajc-Sommerer E, Zumbraegel A, Hoeltl L, Scholz M, et al. Detection and clinical outcome of urinary bladder cancer with 5-aminolevulinic acid-induced fluorescence cystoscopy: a multicenter randomized, double-blind, placebo-controlled trial. Cancer. 2011; 117:938–947.

17. Grossman HB, Stenzl A, Fradet Y, Mynderse LA, Kriegmair M, Witjes JA, et al. Long-term decrease in bladder cancer recurrence with hexaminolevulinate enabled fluorescence cystoscopy. J Urol. 2012; 188:58–62.

18. Cauberg EC, Kloen S, Visser M, de la Rosette JJ, Babjuk M, Soukup V, et al. Narrow band imaging cystoscopy improves the detection of non-muscle-invasive bladder cancer. Urology. 2010; 76:658–663.

19. East JE, Suzuki N, Stavrinidis M, Guenther T, Thomas HJ, Saunders BP. Narrow band imaging for colonoscopic surveillance in hereditary non-polyposis colorectal cancer. Gut. 2008; 57:65–70.

20. Sharma P, Bansal A, Mathur S, Wani S, Cherian R, McGregor D, et al. The utility of a novel narrow band imaging endoscopy system in patients with Barrett's esophagus. Gastrointest Endosc. 2006; 64:167–175.

21. Liu JJ, Droller MJ, Liao JC. New optical imaging technologies for bladder cancer: considerations and perspectives. J Urol. 2012; 188:361–368.

22. Zheng C, Lv Y, Zhong Q, Wang R, Jiang Q. Narrow band imaging diagnosis of bladder cancer: systematic review and meta-analysis. BJU Int. 2012; 110:E680–E687.

23. Miladi M, Peyromaure M, Zerbib M, Saighi D, Debre B. The value of a second transurethral resection in evaluating patients with bladder tumours. Eur Urol. 2003; 43:241–245.

24. Brauers A, Buettner R, Jakse G. Second resection and prognosis of primary high risk superficial bladder cancer: is cystectomy often too early? J Urol. 2001; 165:808–810.

25. Divrik RT, Yildirim U, Zorlu F, Ozen H. The effect of repeat transurethral resection on recurrence and progression rates in patients with T1 tumors of the bladder who received intravesical mitomycin: a prospective, randomized clinical trial. J Urol. 2006; 175:1641–1644.

26. Dalbagni G, Vora K, Kaag M, Cronin A, Bochner B, Donat SM, et al. Clinical outcome in a contemporary series of restaged patients with clinical T1 bladder cancer. Eur Urol. 2009; 56:903–910.

27. Grimm MO, Steinhoff C, Simon X, Spiegelhalder P, Ackermann R, Vogeli TA. Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. J Urol. 2003; 170:433–437.

28. van Rhijn BW, Burger M, Lotan Y, Solsona E, Stief CG, Sylvester RJ, et al. Recurrence and progression of disease in non-muscle-invasive bladder cancer: from epidemiology to treatment strategy. Eur Urol. 2009; 56:430–442.

29. Sylvester RJ, Oosterlinck W, van der Meijden AP. A single immediate postoperative instillation of chemotherapy decreases the risk of recurrence in patients with stage Ta T1 bladder cancer: a meta-analysis of published results of randomized clinical trials. J Urol. 2004; 171:2186–2190.

30. Berrum-Svennung I, Granfors T, Jahnson S, Boman H, Holmang S. A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences. J Urol. 2008; 179:101–105.

31. Gudjonsson S, Adell L, Merdasa F, Olsson R, Larsson B, Davidsson T, et al. Should all patients with non-muscle-invasive bladder cancer receive early intravesical chemotherapy after transurethral resection? The results of a prospective randomised multicentre study. Eur Urol. 2009; 55:773–780.

32. Sylvester RJ, Oosterlinck W, Witjes JA. The schedule and duration of intravesical chemotherapy in patients with non-muscle-invasive bladder cancer: a systematic review of the published results of randomized clinical trials. Eur Urol. 2008; 53:709–719.

33. Shelley MD, Jones G, Cleves A, Wilt TJ, Mason MD, Kynaston HG. Intravesical gemcitabine therapy for non-muscle invasive bladder cancer (NMIBC): a systematic review. BJU Int. 2012; 109:496–505.

34. Malmström PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guérin for non-muscle-invasive bladder cancer. Eur Urol. 2009; 56:247–256.

35. Han RF, Pan JG. Can intravesical bacillus Calmette-Guérin reduce recurrence in patients with superficial bladder cancer? A meta-analysis of randomized trials. Urology. 2006; 67:1216–1223.

36. Jarvinen R, Kaasinen E, Sankila A, Rintala E. FinnBladder Group. Long-term efficacy of maintenance bacillus Calmette-Guérin versus maintenance mitomycin C instillation therapy in frequently recurrent TaT1 tumours without carcinoma in situ: a subgroup analysis of the prospective, randomised FinnBladder I study with a 20-year follow-up. Eur Urol. 2009; 56:260–265.

37. Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical bacillus Calmette-Guerin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized clinical trials. J Urol. 2002; 168:1964–1970.

38. Sylvester RJ, Brausi MA, Kirkels WJ, Hoeltl W, Calais Da, Powell PH, et al. Long-term efficacy results of EORTC genito-urinary group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder. Eur Urol. 2010; 57:766–773.

39. Sylvester RJ, van der Meijden AP, Witjes JA, Kurth K. Bacillus calmette-guerin versus chemotherapy for the intravesical treatment of patients with carcinoma in situ of the bladder: a meta-analysis of the published results of randomized clinical trials. J Urol. 2005; 174:86–91.

40. Bohle A, Jocham D, Bock PR. Intravesical bacillus Calmette-Guerin versus mitomycin C for superficial bladder cancer: a formal meta-analysis of comparative studies on recurrence and toxicity. J Urol. 2003; 169:90–95.

41. Oddens J, Brausi M, Sylvester R, Bono A, van de Beek G, van Andel G, et al. Final results of an EORTC-GU cancers group randomized study of maintenance bacillus Calmette-Guérin in intermediate- and high-risk Ta, T1 papillary carcinoma of the urinary bladder: one-third dose versus full dose and 1 year versus 3 years of maintenance. Eur Urol. 2013; 63:462–472.

42. Herr HW, Sogani PC. Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? J Urol. 2001; 166:1296–1299.

43. Raj GV, Herr H, Serio AM, Donat SM, Bochner BH, Vickers AJ, et al. Treatment paradigm shift may improve survival of patients with high risk superficial bladder cancer. J Urol. 2007; 177:1283–1286.

44. Stein JP, Lieskovsky G, Cote R, Groshen S, Feng AC, Boyd S, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol. 2001; 19:666–675.

45. Gakis G, Efstathiou J, Lerner SP, Cookson MS, Keegan KA, Guru KA, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: radical cystectomy and bladder preservation for muscle-invasive urothelial carcinoma of the bladder. Eur Urol. 2013; 63:45–57.

46. Dorin RP, Daneshmand S, Eisenberg MS, Chandrasoma S, Cai J, Miranda G, et al. Lymph node dissection technique is more important than lymph node count in identifying nodal metastases in radical cystectomy patients: a comparative mapping study. Eur Urol. 2011; 60:946–952.

47. Karl A, Carroll PR, Gschwend JE, Knuchel R, Montorsi F, Stief CG, et al. The impact of lymphadenectomy and lymph node metastasis on the outcomes of radical cystectomy for bladder cancer. Eur Urol. 2009; 55:826–835.

48. Leissner J, Ghoneim MA, Abol-Enein H, Thuroff JW, Franzaring L, Fisch M, et al. Extended radical lymphadenectomy in patients with urothelial bladder cancer: results of a prospective multicenter study. J Urol. 2004; 171:139–144.

49. Kader AK, Richards KA, Krane LS, Pettus JA, Smith JJ, Hemal AK. Robot-assisted laparoscopic vs open radical cystectomy: comparison of complications and perioperative oncological outcomes in 200 patients. BJU Int. 2013; 112:E290–E294.

50. Hautmann RE, Abol-Enein H, Davidsson T, Gudjonsson S, Hautmann SH, Holm HV, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: Urinary diversion. Eur Urol. 2013; 63:67–80.

51. World Health Organization (WHO) Consensus Conference on Bladder Cancer. Hautmann RE, Abol-Enein H, Hafez K, Haro I, Mansson W, et al. Urinary diversion. Urology. 2007; 69:1 Suppl. 17–49.

52. Gore JL, Litwin MS. Urologic Diseases in America Project. Quality of care in bladder cancer: trends in urinary diversion following radical cystectomy. World J Urol. 2009; 27:45–50.

53. Studer UE, Varol C, Danuser H. Orthotopic ileal neobladder. BJU Int. 2004; 93:183–193.

54. Hautmann RE. Surgery illustrated - surgical atlas ileal neobladder. BJU Int. 2010; 105:1024–1035.

55. Mills RD, Studer UE. Metabolic consequences of continent urinary diversion. J Urol. 1999; 161:1057–1066.

56. Kessler TM, Burkhard FC, Perimenis P, Danuser H, Thalmann GN, Hochreiter WW, et al. Attempted nerve sparing surgery and age have a significant effect on urinary continence and erectile function after radical cystoprostatectomy and ileal orthotopic bladder substitution. J Urol. 2004; 172:1323–1327.

57. Park J, Ahn H. Radical cystectomy and orthotopic bladder substitution using ileum. Korean J Urol. 2011; 52:233–240.

58. Porter MP, Penson DF. Health related quality of life after radical cystectomy and urinary diversion for bladder cancer: a systematic review and critical analysis of the literature. J Urol. 2005; 173:1318–1322.

59. Efstathiou JA, Spiegel DY, Shipley WU, Heney NM, Kaufman DS, Niemierko A, et al. Long-term outcomes of selective bladder preservation by combined-modality therapy for invasive bladder cancer: the MGH experience. Eur Urol. 2012; 61:705–711.

60. Krause FS, Walter B, Ott OJ, Haberle L, Weiss C, Rodel C, et al. 15-year survival rates after transurethral resection and radiochemotherapy or radiation in bladder cancer treatment. Anticancer Res. 2011; 31:985–990.

61. Rodel C, Grabenbauer GG, Kuhn R, Papadopoulos T, Dunst J, Meyer M, et al. Combined-modality treatment and selective organ preservation in invasive bladder cancer: long-term results. J Clin Oncol. 2002; 20:3061–3071.

62. Sternberg CN, Bellmunt J, Sonpavde G, Siefker-Radtke AO, Stadler WM, Bajorin DF, et al. ICUD-EAU International Consultation on Bladder Cancer 2012: chemotherapy for urothelial carcinoma-neoadjuvant and adjuvant settings. Eur Urol. 2013; 63:58–66.

63. Grossman HB, Natale RB, Tangen CM, Speights VO, Vogelzang NJ, Trump DL, et al. Neoadjuvant chemotherapy plus cystectomy compared with cystectomy alone for locally advanced bladder cancer. N Engl J Med. 2003; 349:859–866.

64. Herr HW, Faulkner JR, Grossman HB, Natale RB, deVere White R, Sarosdy MF, et al. Surgical factors influence bladder cancer outcomes: a cooperative group report. J Clin Oncol. 2004; 22:2781–2789.

65. Scosyrev E, Ely BW, Messing EM, Speights VO, Grossman HB, Wood DP, et al. Do mixed histological features affect survival benefit from neoadjuvant platinum-based combination chemotherapy in patients with locally advanced bladder cancer? A secondary analysis of Southwest Oncology Group-Directed Intergroup Study (S8710). BJU Int. 2011; 108:693–699.

66. Advanced Bladder Cancer Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: a systematic review and meta-analysis. Lancet. 2003; 361:1927–1934.

67. Advanced Bladder Cancer (ABC) Meta-analysis Collaboration. Neoadjuvant chemotherapy in invasive bladder cancer: update of a systematic review and meta-analysis of individual patient data advanced bladder cancer (ABC) meta-analysis collaboration. Eur Urol. 2005; 48:202–205.

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

69. Porter MP, Kerrigan MC, Donato BM, Ramsey SD. Patterns of use of systemic chemotherapy for Medicare beneficiaries with urothelial bladder cancer. Urol Oncol. 2011; 29:252–258.

70. Pectasides D, Pectasides M, Nikolaou M. Adjuvant and neoadjuvant chemotherapy in muscle invasive bladder cancer: literature review. Eur Urol. 2005; 48:60–67.

71. Leow JJ, Martin-Doyle W, Rajagopal PS, Patel CG, Anderson EM, Rothman AT, et al. Adjuvant chemotherapy for invasive bladder cancer: a 2013 updated systematic review and meta-analysis of randomized trials. Eur Urol. 2013; [Epub]. http://dx.doi.org/10.1016/j.eururo.2013.08.033.