Treatment outcomes of BCG vaccine in patients with T1G3 urothelial cancer – a retrospective analysis
Authors:
Viktor Soukup 1; Otakar Čapoun 1; Tomáš Hanuš 1; Michael Pešl 1; Zuzana Vaľová 1; Zuzana Feherová 1; Libor Zámečník 1; Marko Babjuk 2
Authors‘ workplace:
Urologická klinika 1. LF UK a VFN, Praha
1; Urologická klinika 2. LF UK a FN Motol, Praha
2
Published in:
Ces Urol 2012; 16(4): 230-240
Category:
Original article
Overview
Aim:
The aim of the study was to determine the natural history, recurrence and progression risk after intravesical adjuvant bacillus Calmette-Guérin (BCG) immunotherapy in patients with T1G3 urothelial bladder tumors.
Methods:
Ninety-two patients diagnosed with a T1G3/high grade tumor between 1990 and 2008 were evaluated. All patients received a full induction course (i.e. 6 instillations) of BCG. A subgroup received maintenance BCG treatment following the full initial induction course. The outcomes for each group were compared.
Results:
The median follow-up time was 4.8 (0.3–18.7) years. Recurrence was confirmed in 29 patients, and the recurrence free survival rate at 1, 3 and 5 years was 82, 72 and 66% respectively. There was a significantly higher risk of 3.3% recurrence in patients treated with the induction course of BCG only compared to those receiving maintenance BCG treatment. In the BCG induction plus maintenance group recurrence was detected in 16 patients. The progression free survival at 1, 3 and 5 year follow-ups was 95, 85 and 80%. There was no significant correlation between the risk of progression and concomitant tumor in situ (TIS). On the other hand, BCG maintenance treatment significantly increased the progression-free survival (p = 0.007). Patients without maintenance had 3-times higher risk of progression and 8-times higher risk of subsequent cystectomy. BCG maintenance treatment was the most significant and favorable independent factor for cystectomy-free survival rate, both disease specific and overall survival.
Conclusion:
High-grade T1 (formerly T1G3) bladder cancer has a high propensity for recurrence and progression. Treatment with maintenance BCG was shown to be a significant, favorable, independent factor of recurrence-free, progression-free, cystectomy-free, disease-free and overall survival rate.
Key words:
BCG, progression, recurrence, maintenance BCG treatment, urothelial T1G3 bladder cancer.
Sources
1. Cookson MS, Herr HW, Zhang ZF, et al. The treated natural history of high risk superficial bladder cancer: 15-year outcome. J Urol 1997; 158(1): 62–67.
2. Babjuk M, Oosterlinck W, Sylvester R, et al. EAU Guidelines on non-muscle-invasive urothelial carcinoma of the bladder. Eur Urol 2011; 59: 997–1008.
3. Kulkarni GS, Hakenberg OW, Gschwend JE, et al. An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. Eur Urol. 2010; 57(1): 60–70.
4. 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(1): 146–152.
5. Fritsche HM, Burger M, Svatek RS, et al. Characteristics and outcomes of patients with clinical T1 grade 3 urothelial carcinoma treated with radical cystectomy: results from an international cohort. Eur Urol 2010; 57(2): 300–309.
6. Babjuk M. Intravezikální instilace BCG vakcíny v léčbě povrchových nádorů močového měchýře. Prak Lék 1997; 77: 238–240.
7. Shelley MD, Kynaston H, Court J, et al. A systematic review of intravesical bacillus Calmette-Gue’ rin plus transurethral resection vs transurethral resection alone in Ta and T1 bladder cancer. BJU Int 2001; 88: 209–216.
8. Bohle A, Jocham D, Bock PR. Intravesical bacillus Calmette-Gue’rin versus mitomycin C for superficial bladder cancer: a formal metaanalysis of comparative studies on recurrence and toxicity. J Urol 2003; 169: 90–95.
9. Malmström P-U, Sylvester RJ, Crawford DE, et al. An individual patient data meta-analysis of the long-term outcome of randomised studies comparing intravesical mitomycin C versus bacillus Calmette-Gue’rin for non–muscle-invasive bladder cancer. Eur Urol 2009; 56: 247–256.
10. Bohle A, Bock PR. Intravesical bacilli Calmette-Gue’rin versus mitomycin C in superficial bladder cancer: formal meta-analysis of comparative studies on tumor progression. Urology 2004; 63: 682–686.
11. Sylvester RJ, van der Meijden AP, Lamm DL. Intravesical bacillus Calmette-Gue’ rin reduces the risk of progression in patients with superficial bladder cancer: a meta-analysis of the published results of randomized trials. J Urol 2002; 168: 1964–1970.
12. Herr HW. Is maintenance Bacillus Calmette-Guérin really necessary? Eur Urol 2008; 54: 971–973.
13. 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(5): 766–773.
14. 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.
15. Decobert M, LaRue H, Harel F, et al. Maintenance bacillus Calmette-Guerin in high-risk nonmuscleinvasive bladder cancer: how much is enough? Cancer 2008; 113: 710–716.
16. Badalament RA, Herr HW, Wong GY, et al. A prospective randomized trial of maintenance versus nonmaintenance intravesical BCG therapy of superficial bladder cancer. J Clin Oncol 1987; 5: 441–449.
17. Palou J, Laguna P, Millan-Rodriquez F, et al. Kontrol group and maintenance treatment with BCG for carcinoma in situ and/or high grade bladder tumors. J Urol 2001; 165: 1488–1491.
18. Hudson MA, Ratliff TL, Gillen DP, et al. Single course versus maintenance BCG therapy for superficial bladder tumors: a prospective randomized trial. J Urol 1987; 138: 295–298.
19. Tachibana M, Jitsukawa S, Iigaya T, et al. Komparative study on prophylactic intravesical instillation of BCG and adriamycin for superficial bladder cancers. Nippon Hinyokika Gakkai Zasshi 1989; 80: 1459–1465.
20. Akaza H, Hinotsu S, Aso Y, et al. BCG treatment of existing papillary bladder cancer and carcinoma in situ of the bladder. Cancer 1995; 75: 552–559.
21. Herr HW, Dalbagni G, Donat SM. Bacillus Calmette-Guérin without maintenance therapy for high-risk non-muscle-invasive bladder cancer. Eur Urol 2011; 60(1): 32–36.
22. Shahin O, Thalmann GN, Rentsch C, Mazzucchelli L, Studer UE. A retrospective analysis of 153 patients treated with or without intravesical bacillus Calmette-Guerin for primary stage T1 grade 3 bladder cancer: recurrence, progression and survival. J Urol 2003; 169: 96–100.
23. Dalbagni G, Herr HW, Reuter VE. Impact of a second transurethral resection on the staging of T1 bladder cancer. Urology 2002; 60: 822–824.
24. Herr HW, Sogani PC. Does early cystectomy improve the survival of patients with high risk superficial bladder tumors? J Urol 2001; 166: 1296–1299.
25. Schrier BP, Hollander MP, van Rhijn BW, Kiemeney LA, Witjes JA. Prognosis of muscle-invasive bladder cancer: difference between primary and progressive tumours and implications for therapy. Eur Urol 2004; 45: 292–296.
26. Lambert EH, Pierorazio PM, Olsson CA, et al. The increasing use of intravesical therapies for stage T1 bladder cancer coincides with decreasing survival after cystectomy. BJU Int 2007; 100: 33–36.
27. 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: 1283–1286.
28. Catalona WJ, Hudson MA, Gillen DP, Andriole GL, Ratliff TL. Risks and benefits of repeated courses of intravesical bacillus Calmette-Guerin therapy for superficial bladder cancer. J Urol 1987; 137: 220–224.
29. Nieder AM, Brausi M, Lamm D, et al. Management of stage T1 tumors of the bladder: International Consensus Panel. Urology 2005; 66: 108–125.
30. Dutta SC, Smith Jr JA, Shappell SB, et al. Clinical under staging of high risk nonmuscle invasive urothelial carcinoma treated with radical cystectomy. J Urol 2001; 166: 490–493.
31. Divrik T, Yildirim U, Eroglu AS, Zorlu F, Ozen H. Is a sekond transurethral resection necessary for newly diagnosed pT1 bladder cancer? J Urol 2006; 175: 1258–1261.
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Paediatric urologist Nephrology UrologyArticle was published in
Czech Urology
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