Indian Journal of Urology
: 2012  |  Volume : 28  |  Issue : 2  |  Page : 238--239

Is it time to rethink maintenance Bacillus Calmette-Guerin?

Vivek Venkatramani 

Correspondence Address:
Vivek Venkatramani

How to cite this article:
Venkatramani V. Is it time to rethink maintenance Bacillus Calmette-Guerin?.Indian J Urol 2012;28:238-239

How to cite this URL:
Venkatramani V. Is it time to rethink maintenance Bacillus Calmette-Guerin?. Indian J Urol [serial online] 2012 [cited 2023 Mar 30 ];28:238-239
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In this study, [1] Herr et al. , report their experience with induction Bacillus Calmette-Guerin (BCG) alone in non-muscle invasive bladder cancer (NMIBC) and compare it with the known literature for maintenance BCG.

A cohort of 1021 consecutive patients with bladder cancer from 1995-2006 was reviewed in this study. All patients underwent restaging TURBT (trans-urethral resection of bladder tumor) and subsequently received six weekly instillations of induction BCG. Patients were followed up at three and six months with cystoscopy, urine cytology and TUR biopsy. A complete response was defined as negative cystoscopy, cytology and TUR biopsy at six months. These patients were the focus of further analysis and were eligible to receive another induction course of BCG at each relapse.

A total of 816/1021 (79%) had a complete response to BCG and were included in the study. Of this cohort, 780 (96%) had high-grade tumors, 505 (62%) had associated CIS (carcinoma in situ) and 669 (82%) had multiple/ recurrent tumors. All patients were followed up for five years with three to six-monthly cystoscopy, cytology and repeat TUR as necessary.

The two-year recurrence-free survival rate was 73% and the five-year recurrence-free survival was 46%. Median time to recurrence was 41 months. Five-year progression-free survival was 89% and only 4% of the cohort died of bladder cancer.

Thirty-two percent of patients required repeat induction courses of BCG for recurrence, with 9% requiring a total of three courses. Eight percent were considered treatment failures and underwent cystectomy for recurrent T1 disease.


The practice of maintenance BCG is based on a single large randomised control trial (RCT) - the Southwest Oncology Group (SWOG) trial [2] which demonstrated a further 19%, 6% and 5% reduction in five-year recurrence, 'worsening disease' and death rates respectively, versus induction therapy alone. This trial forms the basis of the meta-analysis by Sylvester et al. , [3] on which the recommendation for maintenance BCG is based. However, this data has several loopholes. First, the follow-up was relatively short (2.5 years) and progression and death rates are clearly proportional to the length of follow-up. [4] Second, only a small percent of tumors were high-risk, leading to a potential underestimation of the actual risk of progression.

Subsequent RCTs have failed to show a statistically significant difference between induction therapy alone and maintenance BCG, despite evidence of a trend to improved progression-free survival. [5] Current guidelines recommend maintenance BCG therapy for 'at least one year'. [6] This is presumably to increase the compliance with the regimen and is based on the meta-analysis of Bohle et al., which showed that at least one year of maintenance BCG was required to demonstrate the superiority of BCG over Mitomycin C in reducing recurrence or progression. [7]

The fact remains that maintenance BCG is toxic with only 16% of patients completing the three-year schedule in the SWOG trial. [1]

With this background in mind, Herr et al. , report their experience with induction therapy alone. This group shows favorable results in comparison with the SWOG trial with a 46% five-year recurrence-free survival (versus 60% for SWOG) and a 20% risk of progression (versus 45% for SWOG). These results appear excellent considering the high proportion of high-grade, multiple tumors, and carcinoma in situ CIS in their cohort.

However, there are a few points that beg clarification.

Nineteen percent of their cohort had received some sort of prior intravesical therapy which is not specified.Twenty-three percent of the cohort was considered tumor-positive at three months but became negative at six months without the need for maintenance therapy - how exactly this could occur is not detailed.The toxicity of repeated induction courses of BCG is not clarified in the article.Perhaps the biggest confounding factor in their results is the fact that all patients, including those with low-grade tumors, had restaging TURs. Complete clearance of the tumor after two TURs could have a significant impact on the risk of recurrence and progression, and quality of TURBT remains a variable whose impact is difficult to quantify.A sub-group analysis with regards to grade and stage of the tumor would have been extremely informative. For example, what was the outcome of TaG3 tumors? Similarly, the outcome of the non-responders to BCG would also have been worth knowing.

Despite these potential limitations, the results of this study remain impressive and should prompt further investigation into the real utility of maintenance BCG and its cost-benefit (vis-à-vis its significant toxicity).


1Herr HW, Dalbagni G, Donnat SM. Bacillus Calmette-Guerin without maintenance therapy for high-risk non-muscle-invasive bladder cancer. Eur Urol 2011;60:32-6.
2Lamm DL, Blumenstein BA, Crissman JD, Montie JE, Gottesman JE, Lowe BA, et al. Maintenance bacillus Calmette-Guerin therapy for recurrent Ta, T1 and carcinoma in situ transitional cell carcinoma of the bladder: A randomized Southwest Oncology Group Study. J Urol 2000;163:1124-9.
3Sylvester RJ, van der MA, 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;168:1964-70.
4Kulkarni GS, Hakenberg OW, Gschwend JE, Thalmann G, Kassouf W, Kamat A, et al. An updated critical analysis of the treatment strategy for newly diagnosed high-grade T1 (previously T1G3) bladder cancer. Eur Urol 2010;57:60-70.
5Malmström PU, Sylvester RJ, Crawford DE, Friedrich M, Krege S, Rintala E, et al. An individual patient meta-analysis of the long-term outcome of randomized studies comparing intravesical mitomycin C versus bacillus Calmette-Guerin for non-muscle-invasive bladder cancer. Eur Urol 2009;56:247-56.
6Babjuk M, Oosterlinck W, Sylvester R, Kaasinen E, Bohle A, Palou J, et al . EAU guidelines on non-muscle invasive urothelial carcinoma of the bladder, the 2011. Eur Urol 2011;59:e33-e38.
7Böhle A, Bock PR. Intravesical bacillus Calmette-Guerin versus mitomycin C in superficial bladder cancer: Formal meta-analysis of comparative studies on tumor progression. Urology 2004;63:682-7.