We appreciate the consideration and thoughtful comments of Drs Singh and Dhakad with regard to this study [1].

As they have pointed out, the BCG-intolerant group seemed to have a favourable prognosis. Indeed, the BCG-intolerant group had a significantly better prognosis than the BCG-refractory group. However, there were no significant differences in stage progression between the BCG-relapsing group and the BCG-intolerant group. For BCG intolerance, we think that it is important to make an effort to improve our compliance with respect to the continuation of BCG therapy, which would minimise the number of BCG-intolerant cases. We previously reported that the discontinuation of BCG therapy (i.e., BCG-intolerant cases) was significantly associated with a higher incidence of tumour recurrence [2]. The development of methods for reducing side-effects without compromising BCG efficacy is necessary. The use of an antibiotic agent or BCG instillation with a reduced dose might reduce the incidence of side-effects and therefore minimise the discontinuance of scheduled BCG-instillation therapy.

There are no guidelines outlining a specific treatment strategy for BCG-relapsing disease, although many BCG-failure cases are attributable to BCG-relapsing disease. In another study [3], we focused in particular on BCG-relapsing tumours, and investigated the risk of subsequent tumour recurrence and stage progression. In that study, some patients with BCG-relapsing tumours with high-risk pathological features, such as G3 and/or pT1 and/or concomitant carcinoma in situ, treated with conservative therapy developed subsequent stage progression, and the 5-year cancer-specific death rate was 12%. Thus, we concluded that such patients should be followed-up closely and counselled on the possible need for radial cystectomy. Of course, the optimal timing for radical cystectomy in BCG-relapsing cases should be established based upon further large and prospective studies.

What we would like to emphasise in this article is that ‘the term, BCG failure’ is inconsistently defined and includes very heterogeneous populations. Although Nieder's classification might not be the best, the concept of stratifying BCG failure is important [4] and according to the concept we need to reconsider and discuss an appropriate therapeutic strategy after initial BCG therapy.


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  • 1
    Shirakawa H, Kikuchi E, Tanaka N et al. Prognostic significance of Bacillus Calmette-Guerin failure classification in non-muscle-invasive bladder cancer. BJU Int 2012 [Epub ahead of print]. DOI: 10.1111/j.1464-410X.2011.10894.x
  • 2
    Takeda T, Kikuchi E, Yuge K et al. Discontinuance of bacille Calmette-Guerin instillation therapy for nonmuscle-invasive bladder cancer has negative effect on tumor recurrence. Urology 2009; 73: 131822
  • 3
    Matsumoto K, Kikuchi E, Shirakawa H et al. Risk of subsequent tumour recurrence and stage progression in bacille Calmette-Guerin relapsing non-muscle-invasive bladder cancer. BJU Int 2012 [Epub ahead of print]. DOI: 10.1111/j.1464-410X.2012.11194.x
  • 4
    O'Donnell MA, Boehle A. Treatment options for BCG failures. World J Urol 2006; 24: 4817