Skip to main content

Advertisement

SpringerLink
Log in

High-risk non-muscle-invasive bladder cancer: update for a better identification and treatment

  • Invited Review
  • Published:
World Journal of Urology Aims and scope Submit manuscript

Abstract

Purpose

Despite standard treatment with transurethral resection (TUR) and adjuvant bacillus Calmette–Guérin (BCG), many high-risk bladder cancers (HRBCs) recur and some progress. Based on a review of the literature, we aimed to establish the optimal current approach for the early diagnosis and management of HRBC.

Methods

A MEDLINE® search was conducted to identify the published literature relating to early identification and treatment for non-muscle-invasive bladder cancer. Particular attention was paid to factors such as quality of TUR, importance of second TUR, substaging, and CIS. In addition, studies on urinary markers, photodynamic diagnosis, predictive clinical and molecular factors for recurrence and progression after BCG, and best management practice were analysed.

Results and conclusions

Good quality of TUR and the implementation of photodynamic diagnosis in selected cases provide a more accurate diagnosis and reduce the risk of residual tumour in HRBC. Although insufficient evidence is available to warrant the use of new urinary molecular markers in isolation, their use in conjunction with cytology and cystoscopy may improve early diagnosis and follow-up. BCG plus maintenance for at least 1 year remains the standard adjuvant treatment for HRBC. Moreover, there is enough evidence to consider the implementation of new specific risk tables for patients treated with BCG. In HRBC patients with poor prognostic factors after TUR, early cystectomy should be considered.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Brausi M, Witjes JA, Lamm D et al (2011) A review of current guidelines and best practice recommendations for the management of nonmuscle invasive bladder cancer by the International Bladder Cancer Group. J Urol 186:2158–2167

    Article  PubMed  Google Scholar 

  2. Sylvester RJ, van der Meijden AP, Oosterlinck W et al (2006) Predicting recurrence and progression in individual patients with stage Ta T1 bladder cancer using EORTC risk tables: a combined analysis of 2596 patients from seven EORTC trials. Eur Urol 49:466–475 (discussion 475–7)

    Article  PubMed  Google Scholar 

  3. Babjuk M, Oosterlinck W, Sylvester R et al (2008) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 54:303–314

    Article  PubMed  Google Scholar 

  4. NCCN (2010) Clinical practise guidelines in oncology: bladder cancer including upper tract tumours and urothelial carcinoma of the prostate. Version 2. Jenkintown. Pennsylvania.NCCN 2010. http://www.ncc.org

  5. AUA (2010) Guideline for the management of nonmuscle invasive bladder cancer (stages Ta,T1, and Tis). http://www.auanet.org

  6. Palou J, Sylvester RJ, Rodriguez Faba O et al (2012) 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-Guerin. Eur Urol 62(1):118–125

    Article  PubMed  Google Scholar 

  7. Fernandez-Gomez J, Madero R, Solsona E et al (2011) The EORTC tables overestimate the risk of recurrence and progression in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: external validation of the EORTC risk tables. Eur Urol 60:423–430

    Article  PubMed  Google Scholar 

  8. Agundez M, Grau L, Palou J et al (2011) Evaluation of the methylation status of tumour suppressor genes for predicting bacillus Calmette-Guerin response in patients with T1G3 high-risk bladder tumours. Eur Urol 60:131–140

    Article  PubMed  CAS  Google Scholar 

  9. Nieder AM, Brausi M, Lamm D et al (2005) Management of stage T1 tumors of the bladder: international consensus panel. Urology 66:108–125

    Article  PubMed  Google Scholar 

  10. Sylvester RJ, van der Meijden A, Witjes JA et al (2005) High-grade Ta urothelial carcinoma and carcinoma in situ of the bladder. Urology 66:90–107

    Article  PubMed  Google Scholar 

  11. Nagele U, Kugler M, Nicklas A et al (2011) Waterjet hydrodissection: first experiences and short-term outcomes of a novel approach to bladder tumor resection. World J Urol 29:423–427

    Article  PubMed  CAS  Google Scholar 

  12. Wolters M, Kramer MW, Becker JU et al (2011) Tm:YAG laser en bloc mucosectomy for accurate staging of primary bladder cancer: early experience. World J Urol 29:429–432

    Article  PubMed  Google Scholar 

  13. Babjuk M, Oosterlinck W, Sylvester R et al (2011) EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder, the 2011 update. Eur Urol 59:997–1008

    Article  PubMed  Google Scholar 

  14. Palou J, Rodriguez O, Segarra J et al (2006) Re: Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy. J Urol 176:407 (author reply 407–8)

    Article  PubMed  CAS  Google Scholar 

  15. Brausi M, Collette L, Kurth K et al (2002) Variability in the recurrence rate at first follow-up cystoscopy after TUR in stage Ta T1 transitional cell carcinoma of the bladder: a combined analysis of seven EORTC studies. Eur Urol 41:523–531

    Article  PubMed  Google Scholar 

  16. Mariappan P, Finney SM, Head E et al (2012) Good quality white-light transurethral resection of bladder tumours (GQ-WLTURBT) with experienced surgeons performing complete resections and obtaining detrusor muscle reduces early recurrence in new non-muscle-invasive bladder cancer: validation across time and place and recommendation for benchmarking. BJU Int 109(11):1666–1673

    Article  PubMed  Google Scholar 

  17. Richterstetter M, Wullich B, Amann K et al (2012) The value of extended transurethral resection of bladder tumour (TURBT) in the treatment of bladder cancer. BJU Int 110(2 Pt 2):E76–E79

    Article  PubMed  Google Scholar 

  18. Jahnson S, Wiklund F, Duchek M et al (2005) Results of second-look resection after primary resection of T1 tumour of the urinary bladder. Scand J Urol Nephrol 39:206–210

    PubMed  Google Scholar 

  19. Schips L, Augustin H, Zigeuner RE et al (2002) Is repeated transurethral resection justified in patients with newly diagnosed superficial bladder cancer? Urology 59:220–223

    Article  PubMed  Google Scholar 

  20. Herr HW (2005) Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy. J Urol 174:2134–2137

    Article  PubMed  Google Scholar 

  21. Rigaud J, Karam G, Braud G et al (2002) T1 bladder tumors: value of a second endoscopic resection. Prog Urol 12:27–30

    PubMed  Google Scholar 

  22. Ozen H, Ekici S, Uygur MC et al (2001) Repeated transurethral resection and intravesical BCG for extensive superficial bladder tumors. J Endourol 15:863–867

    Article  PubMed  CAS  Google Scholar 

  23. Gaya JM, Palou J, Cosentino M et al. (2012) A second transurethral resection could be not necessary in all high grade non-muscle-invasive bladder tumors. Actas Urol Esp (Epub ahead of print; English, Spanish) (2012 Jun 16)

  24. Kim W, Song C, Park S et al (2012) Value of immediate second resection of the tumor bed to improve the effectiveness of transurethral resection of bladder tumor. J Endourol 26(8):1059–1064

    Article  PubMed  Google Scholar 

  25. Thorstenson A, Schumacher MC, Wiklund NP et al (2010) Diagnostic random bladder biopsies: reflections from a population-based cohort of 538 patients. Scand J Urol Nephrol 44:11–19

    Article  PubMed  Google Scholar 

  26. Meijer RP, van Onna IE, Kok ET et al (2011) The risk profiles of three clinical types of carcinoma in situ of the bladder. BJU Int 108:839–843

    PubMed  Google Scholar 

  27. Millan-Rodriguez F, Chechile-Toniolo G, Salvador-Bayarri J et al (2000) Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 164:680–684

    Article  PubMed  CAS  Google Scholar 

  28. Burgues JP, Conde G, Oliva J et al (2011) Hexaminolevulinate photodynamic diagnosis in non-muscle invasive bladder cancer: experience of the BLUE group. Actas Urol Esp 35:439–445

    Article  PubMed  CAS  Google Scholar 

  29. Huguet J, Gaya JM, Sabate S et al (2010) Radical cystectomy in patients with non-muscle invasive bladder cancer who fail BCG therapy. Actas Urol Esp 34:63–70

    Article  PubMed  CAS  Google Scholar 

  30. Green DA, Rink M, Hansen J et al. (2012) Accurate preoperative prediction of non-organ-confined bladder urothelial carcinoma at cystectomy. BJU Int [Epub ahead of print]

  31. Kramer MW, Waalkes S, Serth J et al (2011) Decreased galectin-8 is a strong marker for recurrence in urothelial carcinoma of the bladder. Urol Int 87:143–150

    Article  PubMed  CAS  Google Scholar 

  32. Orsola A, Trias I, Raventos CX et al (2005) Initial high-grade T1 urothelial cell carcinoma: feasibility and prognostic significance of lamina propria invasion microstaging (T1a/b/c) in BCG-treated and BCG-non-treated patients. Eur Urol 48:231–238 (discussion 238)

    Article  PubMed  CAS  Google Scholar 

  33. Cheng L, Montironi R, Davidson DD et al (2009) Staging and reporting of urothelial carcinoma of the urinary bladder. Mod Pathol 22(Suppl 2):S70–S95

    Article  PubMed  Google Scholar 

  34. Chang WC, Chang YH, Pan CC (2012) Prognostic significance in substaging of T1 urinary bladder urothelial carcinoma on transurethral resection. Am J Surg Pathol 36:454–461

    Article  PubMed  Google Scholar 

  35. van Rhijn BW, van der Kwast TH, Alkhateeb SS et al (2012) A new and highly prognostic system to discern T1 bladder cancer substage. Eur Urol 61:378–384

    Article  PubMed  Google Scholar 

  36. Otto W, Denzinger S, Fritsche HM et al (2011) The WHO classification of 1973 is more suitable than the WHO classification of 2004 for predicting survival in pT1 urothelial bladder cancer. BJU Int 107:404–408

    Article  PubMed  Google Scholar 

  37. Vrooman OP, Witjes JA (2008) Urinary markers in bladder cancer. Eur Urol 53:909–916

    Article  PubMed  Google Scholar 

  38. Lotan Y, Shariat SF, Schmitz-Drager BJ et al (2010) Considerations on implementing diagnostic markers into clinical decision making in bladder cancer. Urol Oncol 28:441–448

    Article  PubMed  Google Scholar 

  39. Shariat SF, Karam JA, Lerner SP (2008) Molecular markers in bladder cancer. Curr Opin Urol 18:1–8

    Article  PubMed  Google Scholar 

  40. Shirodkar SP, Lokeshwar VB (2009) Potential new urinary markers in the early detection of bladder cancer. Curr Opin Urol 19:488–493

    Article  PubMed  Google Scholar 

  41. Mowatt G, Zhu S, Kilonzo M et al (2010) Systematic review of the clinical effectiveness and cost-effectiveness of photodynamic diagnosis and urine biomarkers (FISH, ImmunoCyt, NMP22) and cytology for the detection and follow-up of bladder cancer. Health Technol Assess 14:1–331 (iii–iv)

    CAS  Google Scholar 

  42. Hajdinjak T (2008) UroVysion FISH test for detecting urothelial cancers: meta-analysis of diagnostic accuracy and comparison with urinary cytology testing. Urol Oncol 26:646–651

    Article  PubMed  CAS  Google Scholar 

  43. Schmitz-Drager BJ, Beiche B, Tirsar LA et al (2007) Immunocytology in the assessment of patients with asymptomatic microhaematuria. Eur Urol 51:1582–1588 (discussion 1588)

    Article  PubMed  Google Scholar 

  44. Fritsche HM, Burger M, Dietmaier W et al (2010) Multicolor FISH (UroVysion) facilitates follow-up of patients with high-grade urothelial carcinoma of the bladder. Am J Clin Pathol 134:597–603

    Article  PubMed  Google Scholar 

  45. Nguyen CT, Jones JS (2008) Defining the role of NMP22 in bladder cancer surveillance. World J Urol 26:51–58

    Article  PubMed  CAS  Google Scholar 

  46. Huber SSC, Taeger D, Pesch B, Nasterlack M, Leng G, Mayer T, Gawrych KBN, Pelster M, Johnen G, Bontrup H, Wellhäußer H, Bierfreund HG, Wiens CBC, Eberle F, Scheuermann B, Kluckert M, Feil G, Brüning T, Stenzl A et al (2012) (2012) Nuclear matrix protein-22: a prospective evaluation in a population at risk for bladder cancer. Results from the UroScreen study. BJU Int 110(5):699–708

    Article  PubMed  CAS  Google Scholar 

  47. Mian C, Lodde M, Comploj E et al (2005) The value of the ImmunoCyt/uCyt + test in the detection and follow-up of carcinoma in situ of the urinary bladder. Anticancer Res 25:3641–3644

    PubMed  Google Scholar 

  48. Babjuk M, Soukup V, Pesl M et al (2008) Urinary cytology and quantitative BTA and UBC tests in surveillance of patients with pTapT1 bladder urothelial carcinoma. Urology 71:718–722

    Article  PubMed  CAS  Google Scholar 

  49. Raitanen MP, FinnBladder G (2008) The role of BTA stat Test in follow-up of patients with bladder cancer: results from FinnBladder studies. World J Urol 26:45–50

    Article  PubMed  Google Scholar 

  50. Tilki D, Burger M, Dalbagni G et al (2011) Urine markers for detection and surveillance of non-muscle-invasive bladder cancer. Eur Urol 60:484–492

    Article  PubMed  Google Scholar 

  51. Jocham D, Witjes F, Wagner S et al (2005) Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urol 174:862–866 (discussion 866)

    Article  PubMed  Google Scholar 

  52. Jichlinski P, Guillou L, Karlsen SJ et al (2003) Hexyl aminolevulinate fluorescence cystoscopy: new diagnostic tool for photodiagnosis of superficial bladder cancer–a multicenter study. J Urol 170:226–229

    Article  PubMed  Google Scholar 

  53. Kausch I, Sommerauer M, Montorsi F et al (2010) Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urol 57:595–606

    Article  PubMed  Google Scholar 

  54. Geavlete B, Multescu R, Georgescu D et al (2012) Treatment changes and long-term recurrence rates after hexaminolevulinate (HAL) fluorescence cystoscopy: does it really make a difference in patients with non-muscle-invasive bladder cancer (NMIBC)? BJU Int 109:549–556

    Article  PubMed  Google Scholar 

  55. Lapini A, Minervini A, Masala A et al (2012) A comparison of hexaminolevulinate (Hexvix((R))) fluorescence cystoscopy and white-light cystoscopy for detection of bladder cancer: results of the HeRo observational study. Surg Endosc [Epub ahead of print]

  56. Soloway MS, Bruck DS, Kim SS (2003) Expectant management of small, recurrent, noninvasive papillary bladder tumors. J Urol 170:438–441

    Article  PubMed  Google Scholar 

  57. Raj GV, Herr H, Serio AM et al (2007) Treatment paradigm shift may improve survival of patients with high risk superficial bladder cancer. J Urol 177:1283–1286 (discussion 1286)

    Article  PubMed  Google Scholar 

  58. Fernandez-Gomez J, Solsona E, Unda M et al (2008) Prognostic factors in patients with non-muscle-invasive bladder cancer treated with bacillus Calmette-Guerin: multivariate analysis of data from four randomized CUETO trials. Eur Urol 53:992–1001

    Article  PubMed  Google Scholar 

  59. Fernandez-Gomez J, Madero R, Solsona E et al (2009) Predicting nonmuscle invasive bladder cancer recurrence and progression in patients treated with bacillus Calmette-Guerin: the CUETO scoring model. J Urol 182:2195–2203

    Article  PubMed  Google Scholar 

  60. Bertz S, Otto W, Denzinger S et al (2012) Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer. Eur Urol (Epub ahead of print) (May 19)

  61. Shariat SF, Bolenz C, Godoy G et al (2009) Predictive value of combined immunohistochemical markers in patients with pT1 urothelial carcinoma at radical cystectomy. J Urol 182:78–84 (discussion 84)

    Google Scholar 

  62. Palou J, Algaba F, Vera I et al (2009) Protein expression patterns of ezrin are predictors of progression in T1G3 bladder tumours treated with nonmaintenance bacillus Calmette-Guerin. Eur Urol 56:829–836

    Google Scholar 

  63. Fristrup N, Ulhoi BP, Birkenkamp-Demtroder K et al (2012) Cathepsin e, maspin, plk1, and survivin are promising prognostic protein markers for progression in non-muscle invasive bladder cancer. Am J Pathol 180:1824–1834

    Google Scholar 

  64. Zoidakis J, Makridakis M, Zerefos PG et al (2011) Profilin 1 is a potential biomarker for bladder cancer aggressiveness. Mol Cell Proteomics 11(4) [Epub of ahead of print]

  65. Tilki D, Singer BB, Shariat SF et al (2010) CEACAM1: a novel urinary marker for bladder cancer detection. Eur Urol 57:648–654

    Google Scholar 

  66. Reinert T, Modin C, Castano FM et al (2011) Comprehensive genome methylation analysis in bladder cancer: identification and validation of novel methylated genes and application of these as urinary tumor markers. Clin Cancer Res 17:5582–5592

    Google Scholar 

  67. Kulkarni GS, Hakenberg OW, Gschwend JE et al (2010) An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. Eur Urol 57:60–70

    Google Scholar 

  68. Morales A, Eidinger D, Bruce AW (1976) Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol 116:180–183

    Google Scholar 

  69. Lamm DL, Blumenstein BA, Crissman JD et al (2000) Maintenance bacillus Calmette-Guerin immunotherapy for recurrent TA, T1 and carcinoma in situ transitional cell carcinoma of the bladder: a randomized Southwest Oncology Group Study. J Urol 163:1124–1129

    Google Scholar 

  70. Malmstrom PU, Sylvester RJ, Crawford DE et al (2009) An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol 56:247–256

    Google Scholar 

  71. Sylvester RJ, van der MA, Lamm DL (2002) 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 168:1964–1970

  72. Martinez-Pineiro JA, Flores N, Isorna S et al (2002) Long-term follow-up of a randomized prospective trial comparing a standard 81 mg dose of intravesical bacille Calmette-Guerin with a reduced dose of 27 mg in superficial bladder cancer. BJU Int 89:671–680

    Google Scholar 

  73. Schrier BP, Hollander MP, van Rhijn BW et al (2004) Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy. Eur Urol 45:292–296

    Google Scholar 

  74. Kotb AF, Kovac E, Kassouf W et al (2012) Radical cystectomy for clinically muscle invasive bladder cancer: does prior non-invasive disease affect clinical outcomes? World J Urol [Epub ahead of print]

  75. van den Bosch S, Alfred Witjes J (2011) Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: a systematic review. Eur Urol 60:493–500

    Google Scholar 

  76. Shariat SF, Palapattu GS, Amiel GE et al (2006) Characteristics and outcomes of patients with carcinoma in situ only at radical cystectomy. Urology 68:538–542

    Google Scholar 

  77. Malavaud B (2004) T1G3 bladder tumours: the case for radical cystectomy. Eur Urol 45:406–410

    Google Scholar 

  78. Badalato GM, Gaya JM, Hruby G et al (2012) Immediate radical cystectomy vs conservative management for high grade cT1 bladder cancer: is there a survival difference? BJU Int [Epub ahead of print]

Download references

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Urology, Universitat Autonòma de Barcelona, Fundació Puigvert, C/Cartagena, 340-350, 08025, Barcelona, Spain

    Oscar Rodriguez Faba, Joan Palou, Alberto Breda & H. Villavicencio

Authors
  1. Oscar Rodriguez Faba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joan Palou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alberto Breda
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. H. Villavicencio
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Oscar Rodriguez Faba.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Faba, O.R., Palou, J., Breda, A. et al. High-risk non-muscle-invasive bladder cancer: update for a better identification and treatment. World J Urol 30, 833–840 (2012). https://doi.org/10.1007/s00345-012-0967-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00345-012-0967-1

Keywords

Search

Navigation