Critical Reviews in Oncology / Hematology
Volume 76, Issue 2 , Pages 112-126 , November 2010

Diagnosis, evaluation and treatment of carcinoma in situ of the urinary bladder: The state of the art

  • Sean R. Williamson

      Affiliations

    • Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
  • ,
  • Rodolfo Montironi

      Affiliations

    • Institute of Pathological Anatomy and Histopathology, Polytechnic University of the Marche Region (Ancona), United Hospitals, Ancona, Italy
  • ,
  • Antonio Lopez-Beltran

      Affiliations

    • Department of Pathology, Cordoba University, Cordoba, Spain
  • ,
  • Gregory T. MacLennan

      Affiliations

    • Department of Pathology, Case Western Reserve University, Cleveland, OH, USA
  • ,
  • Darrell D. Davidson

      Affiliations

    • Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
  • ,
  • Liang Cheng

      Affiliations

    • Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA
    • Department of Urology, Indiana University School of Medicine, Indianapolis, IN, USA
    • Corresponding Author InformationCorresponding author at: Indiana University School of Medicine, 350 West 11th Street, CPL 4010, Indianapolis 46202, IN, USA. Tel.: +1 317 491 6442; fax: +1 317 491 6419.

,Accepted 7 January 2010.

References 

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–249
  2. Melamed M, Voutsa N, Grabstald H. Natural history and clinical behavior of in situ carcinoma of the human urinary bladder. Cancer. 1964;17:1533–1545
  3. Melicow M. Histological study of vesical urothelium intervening between gross neoplasms in total cytectomy. J Urol. 1952;68:261–279
  4. Cheng L, Cheville JC, Neumann RM, et al. Survival of patients with carcinoma in situ of the urinary bladder. Cancer. 1999;85:2469–2474
  5. Stenzl A, Hennenlotter J, Schilling D. Can we still afford bladder cancer?. Curr Opin Urol. 2008;18:488–492
  6. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. American joint committee on cancer staging manual. 7th ed.. New York: Springer; 2010;
  7. Hodges KB, Lopez-Beltran A, Davidson DD, Montironi R, Cheng L. Urothelial dysplasia and other flat lesions of the urinary bladder: clinicopathologic and molecular features. Hum Pathol; in press.
  8. Cheng L, Lopez-Beltran A, MacLennan GT, Montironi R, Bostwick DG. Neoplasms of the urinary bladder. In:  Bostwick DG,  Cheng L editor. Urologic surgical pathology. 2nd ed.. Philadelphia: Elsevier/Mosby; 2008;p. 259–352
  9. Melicow MMN, Hollowell JW. Intra-urothelial cancer: carcinoma in situ, Bowens's disease of the urinary system: discussion of thirty cases. J Urol. 1952;68:763–772
  10. Lopez-Beltran A, Cheng L, Andersson L, et al. Preneoplastic non-papillary lesions and conditions of the urinary bladder: an update based on the Ancona International Consultation. Virchows Arch. 2002;440:3–11
  11. Takenaka A, Yamada Y, Miyake H, Hara I, Fujisawa M. Clinical outcomes of Bacillus Calmette-Guerin instillation therapy for carcinoma in situ of urinary bladder. Int J Urol. 2008;15:309–313
  12. Johansson SL, Cohen SM. Epidemiology and etiology of bladder cancer. Semin Surg Oncol. 1997;13:291–298
  13. Zeegers MP, Kellen E, Buntinx F, van den Brandt PA. The association between smoking, beverage consumption, diet and bladder cancer: a systematic literature review. World J Urol. 2004;21:392–401
  14. Demir MA, Ryd W, Aldenborg F, Holmang S. Cytopathological expression of different types of urothelial carcinoma in situ in urinary bladder washings. BJU Int. 2003;92:906–910
  15. Fernando H, Thota SS, Burtt G, Waterfall N, Husain I. Importance of red patches diagnosed in cystoscopy for haematuria and lower urinary tract symptoms. Postgrad Med J. 2007;83:62–63
  16. Garbar C, Mascaux C, Wespes E. Is urinary tract cytology still useful for diagnosis of bladder carcinomas? A large series of 592 bladder washings using a five-category classification of different cytological diagnoses. Cytopathology. 2007;18:79–83
  17. Shariat SF, Palapattu GS, Karakiewicz PI, et al. Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ-confined TCC at radical cystectomy. Eur Urol. 2007;51:152–160
  18. Shariat SF, Palapattu GS, Amiel GE, et al. Characteristics and outcomes of patients with carcinoma in situ only at radical cystectomy. Urology. 2006;68:538–542
  19. Vineis P, Esteve J, Hartge P, Hoover R, Silverman DT, Terracini B. Effects of timing and type of tobacco in cigarette-induced bladder cancer. Cancer Res. 1988;48:3849–3852
  20. Fleshner N, Garland J, Moadel A, et al. Influence of smoking status on the disease-related outcomes of patients with tobacco-associated superficial transitional cell carcinoma of the bladder. Cancer. 1999;86:2337–2345
  21. Reulen RC, Kellen E, Buntinx F, Brinkman M, Zeegers MP. A meta-analysis on the association between bladder cancer and occupation. Scand J Urol Nephrol Suppl. 2008;64–78
  22. Castelao JE, Yuan JM, Gago-Dominguez M, Yu MC, Ross RK. Non-steroidal anti-inflammatory drugs and bladder cancer prevention. Br J Cancer. 2000;82:1364–1369
  23. Genkinger JM, De Vivo I, Stampfer MJ, Giovannucci E, Michaud DS. Nonsteroidal antiinflammatory drug use and risk of bladder cancer in the health professionals follow-up study. Int J Cancer. 2007;120:2221–2225
  24. Abol-Enein H. Infection: is it a cause of bladder cancer?. Scand J Urol Nephrol Suppl. 2008;79–84
  25. Cheng L, Cheville JC, Neumann RM, Bostwick DG. Flat intraepithelial lesions of the urinary bladder. Cancer. 2000;88:625–631
  26. Hudson MA, Herr HW. Carcinoma in situ of the bladder. J Urol. 1995;153:564–572
  27. Lopez-Beltran A, Luque RJ, Moreno A, Bollito E, Carmona E, Montironi R. The pagetoid variant of bladder urothelial carcinoma in situ: a clinicopathological study of 11 cases. Virchows Arch. 2002;441:148–153
  28. Swinn MJ, Walker MM, Harbin LJ, et al. Biopsy of the red patch at cystoscopy: is it worthwhile?. Eur Urol. 2004;45:471–474[discussion 474]
  29. Cauberg EC, de Bruin DM, Faber DJ, van Leeuwen TG, de la Rosette JJ, de Reijke TM. A new generation of optical diagnostics for bladder cancer: technology, diagnostic accuracy, and future applications. Eur Urol. 2009;56:287–296
  30. Fradet Y, Grossman HB, Gomella L, et al. A comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of carcinoma in situ in patients with bladder cancer: a phase III, multicenter study. J Urol. 2007;178:68–73[discussion 73]
  31. Colombo R, Naspro R, Bellinzoni P, et al. Photodynamic diagnosis for follow-up of carcinoma in situ of the bladder. Ther Clin Risk Manage. 2007;3:1003–1007
  32. Levi AW, Potter SR, Schoenberg MP, Epstein JI. Clinical significance of denuded urothelium in bladder biopsy. J Urol. 2001;166:457–460
  33. van Oers JM, Adam C, Denzinger S, et al. Chromosome 9 deletions are more frequent than FGFR3 mutations in flat urothelial hyperplasias of the bladder. Int J Cancer. 2006;119:1212–1215
  34. McKenney JK, Gomez JA, Desai S, Lee MW, Amin MB. Morphologic expressions of urothelial carcinoma in situ: a detailed evaluation of its histologic patterns with emphasis on carcinoma in situ with microinvasion. Am J Surg Pathol. 2001;25:356–362
  35. Chan TY, Epstein JI. In situ adenocarcinoma of the bladder. Am J Surg Pathol. 2001;25:892–899
  36. Cheng L, Cheville JC, Neumann RM, Bostwick DG. Natural history of urothelial dysplasia of the bladder. Am J Surg Pathol. 1999;23:443–447
  37. Lopez-Beltran A, Luque RJ, Mazzucchelli R, Scarpelli M, Montironi R. Changes produced in the urothelium by traditional and newer therapeutic procedures for bladder cancer. J Clin Pathol. 2002;55:641–647
  38. McKenney JK, Desai S, Cohen C, Amin MB. Discriminatory immunohistochemical staining of urothelial carcinoma in situ and non-neoplastic urothelium: an analysis of cytokeratin 20, p53, and CD44 antigens. Am J Surg Pathol. 2001;25:1074–1078
  39. Mallofre C, Castillo M, Morente V, Sole M. Immunohistochemical expression of CK20, p53, and Ki-67 as objective markers of urothelial dysplasia. Mod Pathol. 2003;16:187–191
  40. Schrier BP, Vriesema JL, Witjes JA, Kiemeney LA, Schalken JA. The predictive value of p53, p27(kip1), and alpha-catenin for progression in superficial bladder carcinoma. Eur Urol. 2006;50:76–82
  41. Ick K, Schultz M, Stout P, Fan K. Significance of p53 overexpression in urinary bladder transitional cell carcinoma in situ before and after Bacillus Calmette-Guerin treatment. Urology. 1997;49:541–546[discussion 546–7]
  42. Ecke TH, Sachs MD, Lenk SV, Loening SA, Schlechte HH. TP53 gene mutations as an independent marker for urinary bladder cancer progression. Int J Mol Med. 2008;21:655–661
  43. Salinas-Sanchez AS, Lorenzo-Romero JG, Gimenez-Bachs JM, et al. Implications of p53 gene mutations on patient survival in transitional cell carcinoma of the bladder: a long-term study. Urol Oncol. 2008;26:620–626
  44. Gonzalez S, Aubert S, Kerdraon O, et al. Prognostic value of combined p53 and survivin in pT1G3 urothelial carcinoma of the bladder. Am J Clin Pathol. 2008;129:232–237
  45. Shariat SF, Kim J, Raptidis G, Ayala GE, Lerner SP. Association of p53 and p21 expression with clinical outcome in patients with carcinoma in situ of the urinary bladder. Urology. 2003;61:1140–1145
  46. Shariat SF, Pahlavan S, Baseman AG, et al. E-cadherin expression predicts clinical outcome in carcinoma in situ of the urinary bladder. Urology. 2001;57:60–65
  47. Sun W, Herrera GA. E-cadherin expression in urothelial carcinoma in situ, superficial papillary transitional cell carcinoma, and invasive transitional cell carcinoma. Hum Pathol. 2002;33:996–1000
  48. Spruck CH, Ohneseit PF, Gonzalez-Zulueta M, et al. Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Res. 1994;54:784–788
  49. Cheng L, Zhang S, Davidson DD, et al. Molecular determinants of tumor recurrence in the urinary bladder. Future Oncol. 2009;5:843–857
  50. Hartmann A, Schlake G, Zaak D, et al. Occurrence of chromosome 9 and p53 alterations in multifocal dysplasia and carcinoma in situ of human urinary bladder. Cancer Res. 2002;62:809–818
  51. Hopman AH, Kamps MA, Speel EJ, Schapers RF, Sauter G, Ramaekers FC. Identification of chromosome 9 alterations and p53 accumulation in isolated carcinoma in situ of the urinary bladder versus carcinoma in situ associated with carcinoma. Am J Pathol. 2002;161:1119–1125
  52. Zieger K, Marcussen N, Borre M, Orntoft TF, Dyrskjot L. Consistent genomic alterations in carcinoma in situ of the urinary bladder confirm the presence of two major pathways in bladder cancer development. Int J Cancer. 2009;125:2095–2103
  53. Dyrskjot L, Kruhoffer M, Thykjaer T, et al. Gene expression in the urinary bladder: a common carcinoma in situ gene expression signature exists disregarding histopathological classification. Cancer Res. 2004;64:4040–4048
  54. Dyrskjot L, Zieger K, Real FX, et al. Gene expression signatures predict outcome in non-muscle-invasive bladder carcinoma: a multicenter validation study. Clin Cancer Res. 2007;13:3545–3551
  55. Budman LI, Kassouf W, Steinberg JR. Biomarkers for detection and surveillance of bladder cancer. Can Urol Assoc J. 2008;2:212–221
  56. Alvarez A, Lokeshwar VB. Bladder cancer biomarkers: current developments and future implementation. Curr Opin Urol. 2007;17:341–346
  57. Munro NP, Cairns DA, Clarke P, et al. Urinary biomarker profiling in transitional cell carcinoma. Int J Cancer. 2006;119:2642–2650
  58. Sanchez-Carbayo M, Socci ND, Lozano JJ, Haab BB, Cordon-Cardo C. Profiling bladder cancer using targeted antibody arrays. Am J Pathol. 2006;168:93–103
  59. Lokeshwar VB, Soloway MS. Current bladder tumor tests: does their projected utility fulfill clinical necessity?. J Urol. 2001;165:1067–1077
  60. Halling KC, King W, Sokolova IA, et al. A comparison of BTA stat, hemoglobin dipstick, telomerase and Vysis UroVysion assays for the detection of urothelial carcinoma in urine. J Urol. 2002;167:2001–2006
  61. Cohen RA, Brown RS. Clinical practice. Microscopic hematuria. N Engl J Med. 2003;348:2330–2338
  62. Halling KC, King W, Sokolova IA, et al. A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma. J Urol. 2000;164:1768–1775
  63. Gudjonsson S, Isfoss BL, Hansson K, et al. The value of the UroVysion assay for surveillance of non-muscle-invasive bladder cancer. Eur Urol. 2008;54:402–408
  64. Moonen PM, Merkx GF, Peelen P, Karthaus HF, Smeets DF, Witjes JA. UroVysion compared with cytology and quantitative cytology in the surveillance of non-muscle-invasive bladder cancer. Eur Urol. 2007;51:1275–1280[discussion 1280]
  65. Bubendorf L, Grilli B, Sauter G, Mihatsch MJ, Gasser TC, Dalquen P. Multiprobe FISH for enhanced detection of bladder cancer in voided urine specimens and bladder washings. Am J Clin Pathol. 2001;116:79–86
  66. Sarosdy MF, Schellhammer P, Bokinsky G, et al. Clinical evaluation of a multi-target fluorescent in situ hybridization assay for detection of bladder cancer. J Urol. 2002;168:1950–1954
  67. Schwarz S, Rechenmacher M, Filbeck T, et al. Value of multicolour fluorescence in situ hybridisation (UroVysion) in the differential diagnosis of flat urothelial lesions. J Clin Pathol. 2008;61:272–277
  68. Messing EM, Teot L, Korman H, et al. Performance of urine test in patients monitored for recurrence of bladder cancer: a multicenter study in the United States. J Urol. 2005;174:1238–1241
  69. Schroeder GL, Lorenzo-Gomez MF, Hautmann SH, et al. A side by side comparison of cytology and biomarkers for bladder cancer detection. J Urol. 2004;172:1123–1126
  70. Tetu B. Diagnosis of urothelial carcinoma from urine. Mod Pathol. 2009;22(Suppl. 2):S53–S59
  71. Morales A, Eidinger D, Bruce AW. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. J Urol. 1976;116:180–183
  72. Lamm DL, Blumenstein BA, Crawford ED, et al. A randomized trial of intravesical doxorubicin and immunotherapy with Bacille Calmette-Guerin for transitional-cell carcinoma of the bladder. N Engl J Med. 1991;325:1205–1209
  73. Lamm DL. BCG in perspective: advances in the treatment of superficial bladder cancer. Eur Urol. 1995;27(Suppl. 1):2–8
  74. Cookson MS, Herr HW, Zhang ZF, Soloway S, Sogani PC, Fair WR. The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol. 1997;158:62–67
  75. Talic RF, Hargreave TB, Bishop MC, Kirk D, Prescott S. Intravesical Evans Bacille Calmette-Guerin for carcinoma in situ of the urinary bladder. Scottish Urological Oncology Group. Br J Urol. 1994;73:645–648
  76. Lamm DL, Blumenstein BA, Crissman JD, et al. 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. 2000;163:1124–1129
  77. Palou J, Laguna P, Millan-Rodriguez F, Hall RR, Salvador-Bayarri J, Vicente-Rodriguez J. Control group and maintenance treatment with Bacillus Calmette-Guerin for carcinoma in situ and/or high grade bladder tumors. J Urol. 2001;165:1488–1491
  78. Alfred Witjes J, Hendricksen K, Gofrit O, Risi O, Nativ O. Intravesical hyperthermia and mitomycin-C for carcinoma in situ of the urinary bladder: experience of the European Synergo working party. World J Urol. 2009;27:319–324
  79. Grossman HB, O’Donnell MA, Cookson MS, Greenberg RE, Keane TE. Bacillus Calmette-Guérin failures and beyond: contemporary management of non-muscle-invasive bladder cancer. Rev Urol. 2008;10:281–289
  80. Utz D, Hanash K, Farrow G. The plight of the patient with carcinoma in situ of the bladder. J Urol. 1970;103:160–164
  81. Van Gils-Gielen R, Witjes W, Caris C, Debruyne F, Witjes J, Oosterhof G. Risk factors in carcinoma in situ of the urinary bladder. Urology. 1995;45:581–586
  82. Sanderson KM, Roupret M. Upper urinary tract tumour after radical cystectomy for transitional cell carcinoma of the bladder: an update on the risk factors, surveillance regimens and treatments. BJU Int. 2007;100:11–16
  83. Solsona E, Iborra I, Ricos J, Dumont R, Casanova J, Calabuig C. Upper urinary tract involvement in patients with bladder carcinoma in situ (Tis): its impact on management. Urology. 1997;49:347–352
  84. Kenworthy P, Tanguay S, Dinney CP. The risk of upper tract recurrence following cystectomy in patients with transitional cell carcinoma involving the distal ureter. J Urol. 1996;155:501–503
  85. Balaji KC, McGuire M, Grotas J, Grimaldi G, Russo P. Upper tract recurrences following radical cystectomy: an analysis of prognostic factors, recurrence pattern and stage at presentation. J Urol. 1999;162:1603–1606
  86. Sanderson KM, Cai J, Miranda G, Skinner DG, Stein JP. Upper tract urothelial recurrence following radical cystectomy for transitional cell carcinoma of the bladder: an analysis of 1,069 patients with 10-year followup. J Urol. 2007;177:2088–2094
  87. Batista J, Palou J, Iglesias J, et al. Significance of urethral carcinoma in situ in specimens of cystectomy. Eur Urol. 1994;25:313–315
  88. Raj GV, Tal R, Vickers A, et al. Significance of intraoperative ureteral evaluation at radical cystectomy for urothelial cancer. Cancer. 2006;107:2167–2172
  89. Silver D, Stroumbakis N, Russo P, Fair W, Herr H. Ureteral carcinoma in situ at radical cystectomy: does the margin matter?. J Urol. 1997;158:768–771
  90. Yuasa T, Tsuchiya N, Narita S, et al. Radical nephroureterectomy as initial treatment for carcinoma in situ of upper urinary tract. Urology. 2006;68:972–975
  91. Patel SG, Cookson MS, Barocas DA, Clark PE, Smith JAJ, Chang SS. Risk factors for urothelial carcinoma of the prostate in patients undergoing radical cystoprostatectomy for bladder cancer. BJU Int; in press.
  92. Tobisu K, Kanai Y, Sakamoto M, et al. Involvement of the anterior urethra in male patients with transitional cell-carcinoma of the bladder undergoing radical cystectomy with simultaneous urethrectomy. Involvement of the anterior urethra in male patients with transitional cell-carcinoma of the bladder undergoing radical cystectomy with simultaneous urethrectomy. Jpn J Clin Oncol. 1997;27:406–409

PII: S1040-8428(10)00006-5

doi: 10.1016/j.critrevonc.2010.01.005

Critical Reviews in Oncology / Hematology
Volume 76, Issue 2 , Pages 112-126 , November 2010