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 and Program Director
- 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'.)
- 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.
- Dinney CP, Fisher MB, Navai N, et al. Phase I trial of intravesical recombinant adenovirus mediated interferon-α2b formulated in Syn3 for Bacillus Calmette-Guérin failures in nonmuscle invasive bladder cancer. J Urol 2013; 190:850.
- 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 alpha-2b
- Salvage chemohyperthermia
- Electromotive administration of mitomycin
- Experimental intravesical therapies
- Checkpoint inhibition immunotherapy
- Radical cystectomy
- Radiation therapy
- SUMMARY AND RECOMMENDATIONS