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非肌层浸润性膀胱癌的治疗

Author
Michael A O'Donnell, MD, FACS
Section Editor
Seth P Lerner, MD
Deputy Editor
Don S Dizon, MD, FACP
Translators
张鑫, 副主任医师

引言

全球每年大约有390,000例新发膀胱癌，并有150,000例膀胱癌导致的死亡。在世界发达地区，如北美和西欧，这些膀胱癌主要是尿路上皮癌。 (参见“膀胱尿路上皮(移行细胞)癌的流行病学和危险因素”，关于‘流行病学’一节)

大约70%的新发尿路上皮(移行细胞)膀胱癌病例被分类为非肌层浸润癌[1]。这类膀胱癌包括Ta(乳头状)肿瘤、T1(黏膜下侵润)肿瘤和Tis[原位癌(carcinoma in situ, CIS)]，分别占非肌层浸润癌的70%、20%和10%。 (参见“膀胱肿瘤的病理学”)

非肌层浸润性膀胱癌的治疗将在此讨论。膀胱癌的临床表现、诊断和分期，以及尿路上皮膀胱癌的治疗概述参见其他专题。 (参见“膀胱癌的临床表现、诊断和分期”和“膀胱尿路上皮癌的初始处理和治疗概述”)

治疗方法概述

通常在作出非肌层浸润性膀胱癌的诊断时通过对所有可见的膀胱肿瘤进行完全性经尿道膀胱肿瘤切除术(transurethral resection of bladder tumor, TURBT)作为初始治疗。 (参见下文‘经尿道切除术’)

一旦确定诊断，应根据临床因素对患者进行分层，以确定其复发风险的高低。有关浸润深度、组织学级别和有无多中心性病灶的综合信息是决定治疗方法应采用单纯TURBT、TURBT加膀胱内治疗还是膀胱切除术的重要因素。 (参见下文‘风险分层’)

                                             

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Literature review current through: 2017-06 . | This topic last updated: 2017-05-24.
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References
Top
  1. Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 2005; 66:4.
  2. Holmäng S, Andius P, Hedelin H, et al. Stage progression in Ta papillary urothelial tumors: relationship to grade, immunohistochemical expression of tumor markers, mitotic frequency and DNA ploidy. J Urol 2001; 165:1124.
  3. Bostwick DG. Natural history of early bladder cancer. J Cell Biochem Suppl 1992; 16I:31.
  4. Althausen AF, Prout GR Jr, Daly JJ. Non-invasive papillary carcinoma of the bladder associated with carcinoma in situ. J Urol 1976; 116:575.
  5. Pagano F, Garbeglio A, Milani C, et al. Prognosis of bladder cancer. I. Risk factors in superficial transitional cell carcinoma. Eur Urol 1987; 13:145.
  6. Tilki D, Reich O, Svatek RS, et al. Characteristics and outcomes of patients with clinical carcinoma in situ only treated with radical cystectomy: an international study of 243 patients. J Urol 2010; 183:1757.
  7. Chade DC, Shariat SF, Godoy G, et al. Clinical outcomes of primary bladder carcinoma in situ in a contemporary series. J Urol 2010; 184:74.
  8. Wallace DM, Hindmarsh JR, Webb JN, et al. The role of multiple mucosal biopsies in the management of patients with bladder cancer. Br J Urol 1979; 51:535.
  9. Farrow GM, Utz DC, Rife CC, Greene LF. Clinical observations on sixty-nine cases of in situ carcinoma of the urinary bladder. Cancer Res 1977; 37:2794.
  10. Herr HW, Jakse G, Sheinfeld J. The T1 bladder tumor. Semin Urol 1990; 8:254.
  11. Peyromaure M, Zerbib M. T1G3 transitional cell carcinoma of the bladder: recurrence, progression and survival. BJU Int 2004; 93:60.
  12. Alkhateeb SS, Van Rhijn BW, Finelli A, et al. Nonprimary pT1 nonmuscle invasive bladder cancer treated with bacillus Calmette-Guerin is associated with higher risk of progression compared to primary T1 tumors. J Urol 2010; 184:81.
  13. Soloway MS, Sofer M, Vaidya A. Contemporary management of stage T1 transitional cell carcinoma of the bladder. J Urol 2002; 167:1573.
  14. Smith JA Jr, Labasky RF, Cockett AT, et al. Bladder cancer clinical guidelines panel summary report on the management of nonmuscle invasive bladder cancer (stages Ta, T1 and TIS). The American Urological Association. J Urol 1999; 162:1697.
  15. 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.
  16. Heney NM, Ahmed S, Flanagan MJ, et al. Superficial bladder cancer: progression and recurrence. J Urol 1983; 130:1083.
  17. Lutzeyer W, Rübben H, Dahm H. Prognostic parameters in superficial bladder cancer: an analysis of 315 cases. J Urol 1982; 127:250.
  18. Torti FM, Lum BL, Aston D, et al. Superficial bladder cancer: the primacy of grade in the development of invasive disease. J Clin Oncol 1987; 5:125.
  19. Mariappan P, Smith G, Lamb AD, et al. Pattern of recurrence changes in noninvasive bladder tumors observed during 2 decades. J Urol 2007; 177:867.
  20. Burger M, van der Aa MN, van Oers JM, et al. Prediction of progression of non-muscle-invasive bladder cancer by WHO 1973 and 2004 grading and by FGFR3 mutation status: a prospective study. Eur Urol 2008; 54:835.
  21. Lerman RI, Hutter RV, Whitmore WF Jr. Papilloma of the urinary bladder. Cancer 1970; 25:333.
  22. Oosterlinck W, Kurth KH, Schröder F, et al. A prospective European Organization for Research and Treatment of Cancer Genitourinary Group randomized trial comparing transurethral resection followed by a single intravesical instillation of epirubicin or water in single stage Ta, T1 papillary carcinoma of the bladder. J Urol 1993; 149:749.
  23. Wu XR. Urothelial tumorigenesis: a tale of divergent pathways. Nat Rev Cancer 2005; 5:713.
  24. Knowles MA. Molecular subtypes of bladder cancer: Jekyll and Hyde or chalk and cheese? Carcinogenesis 2006; 27:361.
  25. van Rhijn BW, Vis AN, van der Kwast TH, et al. Molecular grading of urothelial cell carcinoma with fibroblast growth factor receptor 3 and MIB-1 is superior to pathologic grade for the prediction of clinical outcome. J Clin Oncol 2003; 21:1912.
  26. Hernández S, López-Knowles E, Lloreta J, et al. Prospective study of FGFR3 mutations as a prognostic factor in nonmuscle invasive urothelial bladder carcinomas. J Clin Oncol 2006; 24:3664.
  27. 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.
  28. Moonen PM, van Balken-Ory B, Kiemeney LA, et al. Prognostic value of p53 for high risk superficial bladder cancer with long-term followup. J Urol 2007; 177:80.
  29. Shariat SF, Lotan Y, Karakiewicz PI, et al. p53 predictive value for pT1-2 N0 disease at radical cystectomy. J Urol 2009; 182:907.
  30. Stadler WM, Lerner SP, Groshen S, et al. Phase III study of molecularly targeted adjuvant therapy in locally advanced urothelial cancer of the bladder based on p53 status. J Clin Oncol 2011; 29:3443.
  31. Dyrskjøt 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.
  32. Allard P, Bernard P, Fradet Y, Têtu B. The early clinical course of primary Ta and T1 bladder cancer: a proposed prognostic index. Br J Urol 1998; 81:692.
  33. Millán-Rodríguez F, Chéchile-Toniolo G, Salvador-Bayarri J, et al. Primary superficial bladder cancer risk groups according to progression, mortality and recurrence. J Urol 2000; 164:680.
  34. Kiemeney LA, Witjes JA, Heijbroek RP, et al. Predictability of recurrent and progressive disease in individual patients with primary superficial bladder cancer. J Urol 1993; 150:60.
  35. Babjuk M, Burger M, Zigeuner R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder: update 2013. Eur Urol 2013; 64:639.
  36. Sylvester RJ, van der Meijden AP, Oosterlinck W, et al. 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 2006; 49:466.
  37. http://www.eortc.be/tools/bladdercalculator/default.htm. (Accessed on February 25, 2011).
  38. Thrasher JB, Frazier HA, Robertson JE, Paulson DF. Does of stage pT0 cystectomy specimen confer a survival advantage in patients with minimally invasive bladder cancer? J Urol 1994; 152:393.
  39. Pagano F, Bassi P, Galetti TP, et al. Results of contemporary radical cystectomy for invasive bladder cancer: a clinicopathological study with an emphasis on the inadequacy of the tumor, nodes and metastases classification. J Urol 1991; 145:45.
  40. 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; 178:2314.
  41. Babjuk M, Oosterlinck W, Sylvester R, et al. EAU guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2008; 54:303.
  42. Lee SE, Jeong IG, Ku JH, et al. Impact of transurethral resection of bladder tumor: analysis of cystectomy specimens to evaluate for residual tumor. Urology 2004; 63:873.
  43. Herr HW. Restaging transurethral resection of high risk superficial bladder cancer improves the initial response to bacillus Calmette-Guerin therapy. J Urol 2005; 174:2134.
  44. Herr HW. The value of a second transurethral resection in evaluating patients with bladder tumors. J Urol 1999; 162:74.
  45. Klän R, Loy V, Huland H. Residual tumor discovered in routine second transurethral resection in patients with stage T1 transitional cell carcinoma of the bladder. J Urol 1991; 146:316.
  46. Dalbagni G, Herr HW, Reuter VE. Impact of a second transurethral resection on the staging of T1 bladder cancer. Urology 2002; 60:822.
  47. Louhelainen J, Wijkström H, Hemminki K. Allelic losses demonstrate monoclonality of multifocal bladder tumors. Int J Cancer 2000; 87:522.
  48. Grimm MO, Steinhoff C, Simon X, et al. Effect of routine repeat transurethral resection for superficial bladder cancer: a long-term observational study. J Urol 2003; 170:433.
  49. Andius P, Holmäng S. Bacillus Calmette-Guérin therapy in stage Ta/T1 bladder cancer: prognostic factors for time to recurrence and progression. BJU Int 2004; 93:980.
  50. 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.
  51. Kausch I, Sommerauer M, Montorsi F, et al. Photodynamic diagnosis in non-muscle-invasive bladder cancer: a systematic review and cumulative analysis of prospective studies. Eur Urol 2010; 57:595.
  52. Daniltchenko DI, Riedl CR, Sachs MD, et al. Long-term benefit of 5-aminolevulinic acid fluorescence assisted transurethral resection of superficial bladder cancer: 5-year results of a prospective randomized study. J Urol 2005; 174:2129.
  53. Denzinger S, Burger M, Walter B, et al. Clinically relevant reduction in risk of recurrence of superficial bladder cancer using 5-aminolevulinic acid-induced fluorescence diagnosis: 8-year results of prospective randomized study. Urology 2007; 69:675.
  54. Filbeck T, Roessler W, Knuechel R, et al. Clinical results of the transurethreal resection and evaluation of superficial bladder carcinomas by means of fluorescence diagnosis after intravesical instillation of 5-aminolevulinic acid. J Endourol 1999; 13:117.
  55. Schmidbauer J, Witjes F, Schmeller N, et al. Improved detection of urothelial carcinoma in situ with hexaminolevulinate fluorescence cystoscopy. J Urol 2004; 171:135.
  56. Hungerhuber E, Stepp H, Kriegmair M, et al. Seven years' experience with 5-aminolevulinic acid in detection of transitional cell carcinoma of the bladder. Urology 2007; 69:260.
  57. Grossman HB, Gomella L, Fradet Y, et al. A phase III, multicenter comparison of hexaminolevulinate fluorescence cystoscopy and white light cystoscopy for the detection of superficial papillary lesions in patients with bladder cancer. J Urol 2007; 178:62.
  58. 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.
  59. Stenzl A, Burger M, Fradet Y, et al. Hexaminolevulinate guided fluorescence cystoscopy reduces recurrence in patients with nonmuscle invasive bladder cancer. J Urol 2010; 184:1907.
  60. Schumacher MC, Holmäng S, Davidsson T, et al. 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.
  61. Stenzl A, Penkoff H, Dajc-Sommerer E, 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.
  62. 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.
  63. Martínez-Piñeiro JA, Jiménez León J, Martínez-Piñeiro L Jr, et al. Bacillus Calmette-Guerin versus doxorubicin versus thiotepa: a randomized prospective study in 202 patients with superficial bladder cancer. J Urol 1990; 143:502.
  64. Shelley MD, Court JB, Kynaston H, et al. Intravesical bacillus Calmette-Guerin versus mitomycin C for Ta and T1 bladder cancer. Cochrane Database Syst Rev 2003; :CD003231.
  65. Böhle A, Bock PR. Intravesical bacille Calmette-Guérin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology 2004; 63:682.
  66. de Reijke TM, Kurth KH, Sylvester RJ, et al. Bacillus Calmette-Guerin versus epirubicin for primary, secondary or concurrent carcinoma in situ of the bladder: results of a European Organization for the Research and Treatment of Cancer--Genito-Urinary Group Phase III Trial (30906). J Urol 2005; 173:405.
  67. Böhle 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.
  68. Prescott S, Jackson AM, Hawkyard SJ, et al. Mechanisms of action of intravesical bacille Calmette-Guérin: local immune mechanisms. Clin Infect Dis 2000; 31 Suppl 3:S91.
  69. Böhle A, Brandau S. Immune mechanisms in bacillus Calmette-Guerin immunotherapy for superficial bladder cancer. J Urol 2003; 170:964.
  70. Mungan NA, Witjes JA. Bacille Calmette-Guérin in superficial transitional cell carcinoma. Br J Urol 1998; 82:213.
  71. Jackson A, Alexandroff A, Fleming D, et al. Bacillus-calmette-guerin (bcg) organisms directly alter the growth of bladder-tumor cells. Int J Oncol 1994; 5:697.
  72. Durek C, Richter E, Basteck A, et al. The fate of bacillus Calmette-Guerin after intravesical instillation. J Urol 2001; 165:1765.
  73. Catalona WJ, Ratliff TL. Bacillus Calmette-Guérin and superficial bladder cancer. Clinical experience and mechanism of action. Surg Annu 1990; 22:363.
  74. Martínez-Piñeiro JA, Martínez-Piñeiro L, Solsona E, et al. Has a 3-fold decreased dose of bacillus Calmette-Guerin the same efficacy against recurrences and progression of T1G3 and Tis bladder tumors than the standard dose? Results of a prospective randomized trial. J Urol 2005; 174:1242.
  75. Pagano F, Bassi P, Piazza N, et al. Improving the efficacy of BCG immunotherapy by dose reduction. Eur Urol 1995; 27 Suppl 1:19.
  76. Agrawal MS, Agrawal M, Bansal S, et al. The safety and efficacy of different doses of bacillus Calmette Guérin in superficial bladder transitional cell carcinoma. Urology 2007; 70:1075.
  77. 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.
  78. Badalament RA, Herr HW, Wong GY, et al. A prospective randomized trial of maintenance versus nonmaintenance intravesical bacillus Calmette-Guérin therapy of superficial bladder cancer. J Clin Oncol 1987; 5:441.
  79. Palou J, Laguna P, Millán-Rodríguez F, et al. Control group and maintenance treatment with bacillus Calmette-Guerin for carcinoma in situ and/or high grade bladder tumors. J Urol 2001; 165:1488.
  80. Hudson MA, Ratliff TL, Gillen DP, et al. Single course versus maintenance bacillus Calmette-Guerin therapy for superficial bladder tumors: a prospective, randomized trial. J Urol 1987; 138:295.
  81. Akaza H, Hinotsu S, Aso Y, et al. Bacillus Calmette-Guérin treatment of existing papillary bladder cancer and carcinoma in situ of the bladder. Four-year results. The Bladder Cancer BCG Study Group. Cancer 1995; 75:552.
  82. Oddens J, Brausi M, Sylvester R, 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.
  83. Saint F, Irani J, Patard JJ, et al. Tolerability of bacille Calmette-Guérin maintenance therapy for superficial bladder cancer. Urology 2001; 57:883.
  84. Colombel M, Saint F, Chopin D, et al. The effect of ofloxacin on bacillus calmette-guerin induced toxicity in patients with superficial bladder cancer: results of a randomized, prospective, double-blind, placebo controlled, multicenter study. J Urol 2006; 176:935.
  85. Swietek N, Waldert M, Rom M, et al. The value of transurethral bladder biopsy after intravesical bacillus Calmette-Guérin instillation therapy for nonmuscle invasive bladder cancer: a retrospective, single center study and cumulative analysis of the literature. J Urol 2012; 188:748.
  86. Lightfoot AJ, Rosevear HM, Nepple KG, O'Donnell MA. Role of routine transurethral biopsy and isolated upper tract cytology after intravesical treatment of high-grade non-muscle invasive bladder cancer. Int J Urol 2012; 19:988.
  87. Catalona WJ, Hudson MA, Gillen DP, et al. Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol 1987; 137:220.
  88. Herr HW, Dalbagni G. Defining bacillus Calmette-Guerin refractory superficial bladder tumors. J Urol 2003; 169:1706.
  89. Shelley MD, Court JB, Kynaston H, et al. Intravesical Bacillus Calmette-Guerin in Ta and T1 Bladder Cancer. Cochrane Database Syst Rev 2000; :CD001986.
  90. Lerner SP, Tangen CM, Sucharew H, et al. Failure to achieve a complete response to induction BCG therapy is associated with increased risk of disease worsening and death in patients with high risk non-muscle invasive bladder cancer. Urol Oncol 2009; 27:155.
  91. Herr HW. Tumour progression and survival in patients with T1G3 bladder tumours: 15-year outcome. Br J Urol 1997; 80:762.
  92. Brake M, Loertzer H, Horsch R, Keller H. Long-term results of intravesical bacillus Calmette-Guérin therapy for stage T1 superficial bladder cancer. Urology 2000; 55:673.
  93. Herr HW, Schwalb DM, Zhang ZF, et al. Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial. J Clin Oncol 1995; 13:1404.
  94. Davis JW, Sheth SI, Doviak MJ, Schellhammer PF. Superficial bladder carcinoma treated with bacillus Calmette-Guerin: progression-free and disease specific survival with minimum 10-year followup. J Urol 2002; 167:494.
  95. Margel D, Tal R, Golan S, et al. Long-term follow-up of patients with Stage T1 high-grade transitional cell carcinoma managed by Bacille Calmette-Guérin immunotherapy. Urology 2007; 69:78.
  96. Rosevear HM, Lightfoot AJ, Nepple KG, O'Donnell MA. Safety and efficacy of intravesical bacillus Calmette-Guérin plus interferon α-2b therapy for nonmuscle invasive bladder cancer in patients with prosthetic devices. J Urol 2010; 184:1920.
  97. Kwak B, Mulhaupt F, Myit S, Mach F. Statins as a newly recognized type of immunomodulator. Nat Med 2000; 6:1399.
  98. Greenwood J, Steinman L, Zamvil SS. Statin therapy and autoimmune disease: from protein prenylation to immunomodulation. Nat Rev Immunol 2006; 6:358.
  99. Hoffmann P, Roumeguère T, Schulman C, van Velthoven R. Use of statins and outcome of BCG treatment for bladder cancer. N Engl J Med 2006; 355:2705.
  100. Orsola A, Cecchini L, Bellmunt J. Statins and the effect of BCG on bladder cancer. N Engl J Med 2007; 356:1276; author reply 1276.
  101. Berglund RK, Savage CJ, Vora KC, et al. An analysis of the effect of statin use on the efficacy of bacillus calmette-guerin treatment for transitional cell carcinoma of the bladder. J Urol 2008; 180:1297.
  102. Tsai HK, Katz MS, Coen JJ, et al. Association of statin use with improved local control in patients treated with selective bladder preservation for muscle-invasive bladder cancer. Urology 2006; 68:1188.
  103. 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.
  104. Friedrich MG, Pichlmeier U, Schwaibold H, et al. Long-term intravesical adjuvant chemotherapy further reduces recurrence rate compared with short-term intravesical chemotherapy and short-term therapy with Bacillus Calmette-Guérin (BCG) in patients with non-muscle-invasive bladder carcinoma. Eur Urol 2007; 52:1123.
  105. Tolley DA, Hargreave TB, Smith PH, et al. Effect of intravesical mitomycin C on recurrence of newly diagnosed superficial bladder cancer: interim report from the Medical Research Council Subgroup on Superficial Bladder Cancer (Urological Cancer Working Party). Br Med J (Clin Res Ed) 1988; 296:1759.
  106. Au JL, Badalament RA, Wientjes MG, et al. Methods to improve efficacy of intravesical mitomycin C: results of a randomized phase III trial. J Natl Cancer Inst 2001; 93:597.
  107. Di Stasi SM, Valenti M, Verri C, et al. Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial. Lancet Oncol 2011; 12:871.
  108. Colombo R, Da Pozzo LF, Salonia A, et al. Multicentric study comparing intravesical chemotherapy alone and with local microwave hyperthermia for prophylaxis of recurrence of superficial transitional cell carcinoma. J Clin Oncol 2003; 21:4270.
  109. Thrasher JB, Crawford ED. Complications of intravesical chemotherapy. Urol Clin North Am 1992; 19:529.
  110. Colver GB, Inglis JA, McVittie E, et al. Dermatitis due to intravesical mitomycin C: a delayed-type hypersensitivity reaction? Br J Dermatol 1990; 122:217.
  111. Serretta V, Galuffo A, Pavone C, et al. Gemcitabine in intravesical treatment of Ta-T1 transitional cell carcinoma of bladder: Phase I-II study on marker lesions. Urology 2005; 65:65.
  112. Gårdmark T, Carringer M, Beckman E, et al. Randomized phase II marker lesion study evaluating effect of scheduling on response to intravesical gemcitabine in recurrent Stage Ta urothelial cell carcinoma of the bladder. Urology 2005; 66:527.
  113. Dalbagni G, Russo P, Bochner B, et al. Phase II trial of intravesical gemcitabine in bacille Calmette-Guérin-refractory transitional cell carcinoma of the bladder. J Clin Oncol 2006; 24:2729.
  114. Mohanty NK, Nayak RL, Vasudeva P, Arora RP. Intravesicle gemcitabine in management of BCG refractory superficial TCC of urinary bladder-our experience. Urol Oncol 2008; 26:616.
  115. Skinner EC, Goldman B, Sakr WA, et al. SWOG S0353: Phase II trial of intravesical gemcitabine in patients with nonmuscle invasive bladder cancer and recurrence after 2 prior courses of intravesical bacillus Calmette-Guérin. J Urol 2013; 190:1200.
  116. Jones G, Cleves A, Wilt TJ, et al. Intravesical gemcitabine for non-muscle invasive bladder cancer. Cochrane Database Syst Rev 2012; 1:CD009294.
  117. Steinberg G, Bahnson R, Brosman S, et al. Efficacy and safety of valrubicin for the treatment of Bacillus Calmette-Guerin refractory carcinoma in situ of the bladder. The Valrubicin Study Group. J Urol 2000; 163:761.
  118. McKiernan JM, Masson P, Murphy AM, et al. Phase I trial of intravesical docetaxel in the management of superficial bladder cancer refractory to standard intravesical therapy. J Clin Oncol 2006; 24:3075.
  119. Laudano MA, Barlow LJ, Murphy AM, et al. Long-term clinical outcomes of a phase I trial of intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to standard intravesical therapy. Urology 2010; 75:134.
  120. Barlow L, McKiernan J, Sawczuk I, Benson M. A single-institution experience with induction and maintenance intravesical docetaxel in the management of non-muscle-invasive bladder cancer refractory to bacille Calmette-Guérin therapy. BJU Int 2009; 104:1098.
  121. Barlow LJ, McKiernan JM, Benson MC. Long-term survival outcomes with intravesical docetaxel for recurrent nonmuscle invasive bladder cancer after previous bacillus Calmette-Guérin therapy. J Urol 2013; 189:834.
  122. Rajala P, Liukkonen T, Raitanen M, et al. Transurethral resection with perioperative instilation on interferon-alpha or epirubicin for the prophylaxis of recurrent primary superficial bladder cancer: a prospective randomized multicenter study--Finnbladder III. J Urol 1999; 161:1133.
  123. Berrum-Svennung I, Granfors T, Jahnson S, et al. A single instillation of epirubicin after transurethral resection of bladder tumors prevents only small recurrences. J Urol 2008; 179:101.
  124. van der Meijden AP, Brausi M, Zambon V, et al. Intravesical instillation of epirubicin, bacillus Calmette-Guerin and bacillus Calmette-Guerin plus isoniazid for intermediate and high risk Ta, T1 papillary carcinoma of the bladder: a European Organization for Research and Treatment of Cancer genito-urinary group randomized phase III trial. J Urol 2001; 166:476.
  125. Sylvester RJ, Brausi MA, Kirkels WJ, 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.
  126. Borden EC, Groveman DS, Nasu T, et al. Antiproliferative activities of interferons against human bladder carcinoma cell lines in vitro. J Urol 1984; 132:800.
  127. Hawkyard S, James K, Prescott S, et al. The effects of recombinant human interferon-gamma on a panel of human bladder cancer cell lines. J Urol 1991; 145:1078.
  128. Sargent ER, Williams RD. Immunotherapeutic alternatives in superficial bladder cancer. Interferon, interleukin-2, and keyhole-limpet hemocyanin. Urol Clin North Am 1992; 19:581.
  129. Jimenez-Cruz JF, Vera-Donoso CD, Leiva O, et al. Intravesical immunoprophylaxis in recurrent superficial bladder cancer (Stage T1): multicenter trial comparing bacille Calmette-Guérin and interferon-alpha. Urology 1997; 50:529.
  130. Nepple KG, Lightfoot AJ, Rosevear HM, et al. Bacillus Calmette-Guérin with or without interferon α-2b and megadose versus recommended daily allowance vitamins during induction and maintenance intravesical treatment of nonmuscle invasive bladder cancer. J Urol 2010; 184:1915.
  131. Joudi FN, Smith BJ, O'Donnell MA, National BCG-Interferon Phase 2 Investigator Group. Final results from a national multicenter phase II trial of combination bacillus Calmette-Guérin plus interferon alpha-2B for reducing recurrence of superficial bladder cancer. Urol Oncol 2006; 24:344.
  132. Lamm D, Brausi M, O'Donnell MA, Witjes JA. Interferon alfa in the treatment paradigm for non-muscle-invasive bladder cancer. Urol Oncol 2014; 32:35.e21.
  133. Prout GR Jr, Koontz WW Jr, Coombs LJ, et al. Long-term fate of 90 patients with superficial bladder cancer randomly assigned to receive or not to receive thiotepa. J Urol 1983; 130:677.
  134. Hollister D Jr, Coleman M. Hematologic effects of intravesicular thiotepa therapy for bladder carcinoma. JAMA 1980; 244:2065.
  135. Silberberg JM, Zarrabi MH. Acute nonlymphocytic leukemia after thiotepa instillation into the bladder: report of 2 cases and review of the literature. J Urol 1987; 138:402.
  136. Lee CT, Dunn RL, Ingold C, et al. Early-stage bladder cancer surveillance does not improve survival if high-risk patients are permitted to progress to muscle invasion. Urology 2007; 69:1068.
  137. Weiss C, Wolze C, Engehausen DG, et al. Radiochemotherapy after transurethral resection for high-risk T1 bladder cancer: an alternative to intravesical therapy or early cystectomy? J Clin Oncol 2006; 24:2318.
  138. Harland SJ, Kynaston H, Grigor K, et al. A randomized trial of radical radiotherapy for the management of pT1G3 NXM0 transitional cell carcinoma of the bladder. J Urol 2007; 178:807.
  139. Herr HW. Extravesical tumor relapse in patients with superficial bladder tumors. J Clin Oncol 1998; 16:1099.
  140. Stephenson J. Diabetes drug may be associated with increase in risk of bladder cancer. JAMA 2011; 306:143.
  141. Lewis JD, Ferrara A, Peng T, et al. Risk of bladder cancer among diabetic patients treated with pioglitazone: interim report of a longitudinal cohort study. Diabetes Care 2011; 34:916.
  142. Herr HW, Badalament RA, Amato DA, et al. Superficial bladder cancer treated with bacillus Calmette-Guerin: a multivariate analysis of factors affecting tumor progression. J Urol 1989; 141:22.
  143. Hall RR, Parmar MK, Richards AB, Smith PH. Proposal for changes in cystoscopic follow up of patients with bladder cancer and adjuvant intravesical chemotherapy. BMJ 1994; 308:257.
  144. Evans CP. Follow-up surveillance strategies for genitourinary malignancies. Cancer 2002; 94:2892.
  145. Schrag D, Hsieh LJ, Rabbani F, et al. Adherence to surveillance among patients with superficial bladder cancer. J Natl Cancer Inst 2003; 95:588.
  146. Sanderson KM, Cai J, Miranda G, et al. 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.
  147. Schwartz CB, Bekirov H, Melman A. Urothelial tumors of upper tract following treatment of primary bladder transitional cell carcinoma. Urology 1992; 40:509.
  148. Hurle R, Losa A, Manzetti A, Lembo A. Upper urinary tract tumors developing after treatment of superficial bladder cancer: 7-year follow-up of 591 consecutive patients. Urology 1999; 53:1144.
  149. Canales BK, Anderson JK, Premoli J, Slaton JW. Risk factors for upper tract recurrence in patients undergoing long-term surveillance for stage ta bladder cancer. J Urol 2006; 175:74.
  150. Wright JL, Hotaling J, Porter MP. Predictors of upper tract urothelial cell carcinoma after primary bladder cancer: a population based analysis. J Urol 2009; 181:1035.
  151. Herr HW, Cookson MS, Soloway SM. Upper tract tumors in patients with primary bladder cancer followed for 15 years. J Urol 1996; 156:1286.
  152. Miller EB, Eure GR, Schellhammer PF. Upper tract transitional cell carcinoma following treatment of superficial bladder cancer with BCG. Urology 1993; 42:26.
  153. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
  154. Schwalb MD, Herr HW, Sogani PC, et al. Positive urinary cytology following a complete response to intravesical bacillus Calmette-Guerin therapy: pattern of recurrence. J Urol 1994; 152:382.
  155. Rabbani F, Perrotti M, Russo P, Herr HW. Upper-tract tumors after an initial diagnosis of bladder cancer: argument for long-term surveillance. J Clin Oncol 2001; 19:94.
  156. Herr HW, Donat SM. Prostatic tumor relapse in patients with superficial bladder tumors: 15-year outcome. J Urol 1999; 161:1854.
  157. Huguet J, Crego M, Sabaté S, et al. Cystectomy in patients with high risk superficial bladder tumors who fail intravesical BCG therapy: pre-cystectomy prostate involvement as a prognostic factor. Eur Urol 2005; 48:53.
  158. Donat SM, North A, Dalbagni G, Herr HW. Efficacy of office fulguration for recurrent low grade papillary bladder tumors less than 0.5 cm. J Urol 2004; 171:636.
  159. Soloway MS, Bruck DS, Kim SS. Expectant management of small, recurrent, noninvasive papillary bladder tumors. J Urol 2003; 170:438.
  160. Witjes JA, Debruyne FM. Intravesical chemotherapy. In: Genitourinary Oncology, 2nd, Vogelzang NJ, Scardino PT, Shipley WU, Coffey DS (Eds), Lipincott, Philadelphia 2000. p.394.
  161. O'Donnell MA, Boehle A. Treatment options for BCG failures. World J Urol 2006; 24:481.
  162. Oosterlinck W, Lobel B, Jakse G, et al. Guidelines on bladder cancer. Eur Urol 2002; 41:105.
  163. Raj GV, Herr H, Serio AM, et al. Treatment paradigm shift may improve survival of patients with high risk superficial bladder cancer. J Urol 2007; 177:1283.
  164. Luciani LG, Neulander E, Murphy WM, Wajsman Z. Risk of continued intravesical therapy and delayed cystectomy in BCG-refractory superficial bladder cancer: an investigational approach. Urology 2001; 58:376.
  165. O'Donnell MA, Krohn J, DeWolf WC. Salvage intravesical therapy with interferon-alpha 2b plus low dose bacillus Calmette-Guerin is effective in patients with superficial bladder cancer in whom bacillus Calmette-Guerin alone previously failed. J Urol 2001; 166:1300.
  166. Herr HW, Sogani PC. Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? J Urol 2001; 166:1296.