Management of recurrent or persistent non-muscle invasive bladder cancer
- Peter Black, MD, FACS, FRCSC
Peter Black, MD, FACS, FRCSC
- Khosrowshahi Chair in Bladder Cancer Research
- Associate Professor
- Department of Urologic Sciences
- University of British Columbia
- Vancouver Prostate Centre
- Wassim Kassouf, MD, CM, FRCS
Wassim Kassouf, MD, CM, FRCS
- Professor of Surgery (Urology)
- McGill University Health Center
Approximately 70 percent of new urothelial (formerly called transitional cell) bladder cancer cases are classified as non-muscle invasive . Non-muscle invasive bladder cancer includes Ta, T1 (submucosal invasive) tumors, and Tis (carcinoma in situ [CIS]), which account for approximately 70, 20, and 10 percent of non-muscle invasive cancers, respectively.
The rate of recurrence of non-muscle invasive bladder cancer surpasses that of all other cancers , and the majority of patients will experience a recurrence. Management of recurrent disease is, therefore, a critical concern in patients with non-muscle invasive bladder cancer. Determining optimal therapy, however, is complicated by the heterogeneity of disease in these patients.
Even with optimal treatment, patients with non-muscle invasive disease are at high risk of recurrence with further non-muscle invasive disease or of progression to more advanced disease. The management of recurrent or persistent non-muscle invasive disease is discussed in this topic.
The initial management and follow-up of patients with non-muscle invasive bladder cancer is discussed separately. (See "Treatment of primary non-muscle invasive urothelial bladder cancer".)
RISK OF RECURRENCE
Data on the risk of recurrence and progression in patients with non-muscle invasive bladder cancer are derived from large series that included patients with both primary and recurrent disease. These issues are discussed separately. (See "Treatment of primary non-muscle invasive urothelial bladder cancer", section on 'Risk stratification'.)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Kirkali Z, Chan T, Manoharan M, et al. Bladder cancer: epidemiology, staging and grading, and diagnosis. Urology 2005; 66:4.
- http://www.cancer.ca/en/cancer-information/cancer-type/ovarian/risks/?region=on http://www.cancer.ca/en/cancer-information/cancer-type/ovarian/risks/?region=on (Accessed on March 28, 2014).
- Jarow JP, Lerner SP, Kluetz PG, et al. Clinical trial design for the development of new therapies for nonmuscle-invasive bladder cancer: report of a Food and Drug Administration and American Urological Association public workshop. Urology 2014; 83:262.
- Lerner SP, Dinney C, Kamat A, et al. Clarification of Bladder Cancer Disease States Following Treatment of Patients with Intravesical BCG. Bladder Cancer 2015; 1:29.
- Jarow J, Maher VE, Tang S, et al. Development of Systemic and Topical Drugs to Treat Non-muscle Invasive Bladder Cancer. Bladder Cancer 2015; 1:133.
- Gallagher BL, Joudi FN, Maymí JL, O'Donnell MA. Impact of previous bacille Calmette-Guérin failure pattern on subsequent response to bacille Calmette-Guérin plus interferon intravesical therapy. Urology 2008; 71:297.
- Steinberg RL, Thomas LJ, O'Donnell MA. Bacillus Calmette-Guerin (BCG) Treatment Failures in Non-Muscle Invasive Bladder Cancer: What Truly Constitutes Unresponsive Disease. Bl Cancer 2015; 1:105.
- Steinberg RL, Thomas LJ, Mott SL, O’Donnell MA. Bacillus Calmette-Guérin (BCG) Treatment Failures with Non-Muscle Invasive Bladder Cancer: A Data-Driven Definition for BCG Unresponsive Disease. Bl Cancer 2016; In press: 1-10.
- Mmeje CO, Guo CC, Shah JB, et al. Papillary Recurrence of Bladder Cancer at First Evaluation after Induction Bacillus Calmette-Guérin Therapy: Implication for Clinical Trial Design. Eur Urol 2016; 70:778.
- Ray ER, Chatterton K, Khan MS, et al. Hexylaminolaevulinate fluorescence cystoscopy in patients previously treated with intravesical bacille Calmette-Guérin. BJU Int 2010; 105:789.
- Mount A, Williams SB, Dinney CPN, et al. Examining the effect that prior bladder manipulation and BCG treatment have on false positive rates of blue-light cystoscopy biopsies. J Clin Oncol 2016; 34 (suppl 2S; abstr 416).
- Giannarini G, Birkhäuser FD, Recker F, et al. Bacillus Calmette-Guérin failure in patients with non-muscle-invasive urothelial carcinoma of the bladder may be due to the urologist's failure to detect urothelial carcinoma of the upper urinary tract and urethra. Eur Urol 2014; 65:825.
- 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.
- Soloway MS, Bruck DS, Kim SS. Expectant management of small, recurrent, noninvasive papillary bladder tumors. J Urol 2003; 170:438.
- Herr HW, Donat SM. A re-staging transurethral resection predicts early progression of superficial bladder cancer. BJU Int 2006; 97:1194.
- Perlis N, Zlotta AR, Beyene J, et al. Immediate post-transurethral resection of bladder tumor intravesical chemotherapy prevents non-muscle-invasive bladder cancer recurrences: an updated meta-analysis on 2548 patients and quality-of-evidence review. Eur Urol 2013; 64:421.
- Sylvester RJ, Oosterlinck W, Holmang S, et al. Systematic Review and Individual Patient Data Meta-analysis of Randomized Trials Comparing a Single Immediate Instillation of Chemotherapy After Transurethral Resection with Transurethral Resection Alone in Patients with Stage pTa-pT1 Urothelial Carcinoma of the Bladder: Which Patients Benefit from the Instillation? Eur Urol 2016; 69:231.
- 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.
- Kamat AM, Witjes JA, Brausi M, et al. Defining and treating the spectrum of intermediate risk nonmuscle invasive bladder cancer. J Urol 2014; 192:305.
- 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.
- 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.
- Solsona E, Iborra I, Dumont R, et al. The 3-month clinical response to intravesical therapy as a predictive factor for progression in patients with high risk superficial bladder cancer. J Urol 2000; 164:685.
- Herr HW. Progression of stage T1 bladder tumors after intravesical bacillus Calmette-Guerin. J Urol 1991; 145:40.
- Malmström PU, Wijkström H, Lundholm C, et al. 5-year followup of a randomized prospective study comparing mitomycin C and bacillus Calmette-Guerin in patients with superficial bladder carcinoma. Swedish-Norwegian Bladder Cancer Study Group. J Urol 1999; 161:1124.
- 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.
- 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.
- 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.
- O'Donnell MA, Boehle A. Treatment options for BCG failures. World J Urol 2006; 24:481.
- 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.
- Dinney CP, Greenberg RE, Steinberg GD. Intravesical valrubicin in patients with bladder carcinoma in situ and contraindication to or failure after bacillus Calmette-Guérin. Urol Oncol 2013; 31:1635.
- Di Lorenzo G, Perdonà S, Damiano R, et al. Gemcitabine versus bacille Calmette-Guérin after initial bacille Calmette-Guérin failure in non-muscle-invasive bladder cancer: a multicenter prospective randomized trial. Cancer 2010; 116:1893.
- 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.
- Sternberg IA, Dalbagni G, Chen LY, et al. Intravesical gemcitabine for high risk, nonmuscle invasive bladder cancer after bacillus Calmette-Guérin treatment failure. J Urol 2013; 190:1686.
- 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.
- Nativ O, Witjes JA, Hendricksen K, et al. Combined thermo-chemotherapy for recurrent bladder cancer after bacillus Calmette-Guerin. J Urol 2009; 182:1313.
- Arends TJ, van der Heijden AG, Witjes JA. Combined chemohyperthermia: 10-year single center experience in 160 patients with nonmuscle invasive bladder cancer. J Urol 2014; 192:708.
- Morales A, Phadke K, Steinhoff G. Intravesical mycobacterial cell wall-DNA complex in the treatment of carcinoma in situ of the bladder after standard intravesical therapy has failed. J Urol 2009; 181:1040.
- Kamat A, Amrhein J, Cohen Z, Champagne M. Efficacy of Mycobacterium phlei Cell Wall-Nucleic Acid Complex (MCNA) in BCG- Unresponsive Patients. Paper presented at: European Association of Urology; March 12, 2016, 2016; Munich.
- Shore ND, Boorjian SA, Canter DJ, et al. Intravesical rAd-IFNα/Syn3 for Patients With High-Grade, Bacillus Calmette-Guerin-Refractory or Relapsed Non-Muscle-Invasive Bladder Cancer: A Phase II Randomized Study. J Clin Oncol 2017; 35:3410.
- Kowalski M, Entwistle J, Cizeau J, et al. A Phase I study of an intravesically administered immunotoxin targeting EpCAM for the treatment of nonmuscle-invasive bladder cancer in BCGrefractory and BCG-intolerant patients. Drug Des Devel Ther 2010; 4:313.
- Kowalski M, Guindon J, Brazas L, et al. A phase II study of oportuzumab monatox: an immunotoxin therapy for patients with noninvasive urothelial carcinoma in situ previously treated with bacillus Calmette-Guérin. J Urol 2012; 188:1712.
- Sidi AA, Ohana P, Benjamin S, et al. Phase I/II marker lesion study of intravesical BC-819 DNA plasmid in H19 over expressing superficial bladder cancer refractory to bacillus Calmette-Guerin. J Urol 2008; 180:2379.
- Gofrit ON, Benjamin S, Halachmi S, et al. DNA based therapy with diphtheria toxin-A BC-819: a phase 2b marker lesion trial in patients with intermediate risk nonmuscle invasive bladder cancer. J Urol 2014; 191:1697.
- Shabsigh A, Korets R, Vora KC, et al. Defining early morbidity of radical cystectomy for patients with bladder cancer using a standardized reporting methodology. Eur Urol 2009; 55:164.
- Aziz A, May M, Burger M, et al. Prediction of 90-day mortality after radical cystectomy for bladder cancer in a prospective European multicenter cohort. Eur Urol 2014; 66:156.
- van den Bosch S, Alfred Witjes J. Long-term cancer-specific survival in patients with high-risk, non-muscle-invasive bladder cancer and tumour progression: a systematic review. Eur Urol 2011; 60:493.
- 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.
- 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.
- Denzinger S, Fritsche HM, Otto W, et al. Early versus deferred cystectomy for initial high-risk pT1G3 urothelial carcinoma of the bladder: do risk factors define feasibility of bladder-sparing approach? Eur Urol 2008; 53:146.
- Herr HW, Sogani PC. Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? J Urol 2001; 166:1296.
- Nieder AM, Simon MA, Kim SS, et al. Radical cystectomy after bacillus Calmette-Guérin for high-risk Ta, T1, and carcinoma in situ: defining the risk of initial bladder preservation. Urology 2006; 67:737.
- 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.
- Jäger W, Thomas C, Haag S, et al. Early vs delayed radical cystectomy for 'high-risk' carcinoma not invading bladder muscle: delay of cystectomy reduces cancer-specific survival. BJU Int 2011; 108:E284.
- Mata DA, Groshen S, Von Rundstedt FC, et al. Variability in surgical quality in a phase III clinical trial of radical cystectomy in patients with organ-confined, node-negative urothelial carcinoma of the bladder. J Surg Oncol 2015; 111:923.
- Stein JP, Penson DF. Invasive T1 bladder cancer: indications and rationale for radical cystectomy. BJU Int 2008; 102:270.
- Stein JP, Lieskovsky G, Cote R, et al. Radical cystectomy in the treatment of invasive bladder cancer: long-term results in 1,054 patients. J Clin Oncol 2001; 19:666.
- Freeman JA, Esrig D, Stein JP, et al. Radical cystectomy for high risk patients with superficial bladder cancer in the era of orthotopic urinary reconstruction. Cancer 1995; 76:833.
- 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.
- 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.
- RISK OF RECURRENCE
- DEFINITION OF RECURRENCE STATES
- Recurrence without prior adjuvant intravesical therapy
- Recurrence after prior adjuvant intravesical therapy
- DIAGNOSIS OF RECURRENCE
- TREATMENT OF RECURRENT DISEASE
- Transurethral resection of bladder tumor
- - Single-dose perioperative chemotherapy
- No prior adjuvant intravesical therapy
- Salvage intravesical therapy
- - Intravesical BCG
- - Other salvage intravesical regimens
- BCG plus interferon alfa-2b
- Salvage chemohyperthermia
- Electromotive administration of mitomycin
- Experimental intravesical therapies
- Checkpoint inhibition immunotherapy
- Radical cystectomy
- Radiation therapy
- SUMMARY AND RECOMMENDATIONS