Prognostic significance of Bacillus Calmette‐Guérin failure classification in non‐muscle‐invasive bladder cancer
Authors: Shirakawa Hiroshi , Kikuchi Eiji , Tanaka Nobuyuki , Matsumoto Kazuhiro , Miyajima Akira , Nakamura So , Oya Mototsugu 
Published: February 2012

Study Type – Prognosis (case series)Level of Evidence 4What's known on the subject? and What does the study add?Adjuvant intravesical BCG therapy is the most effective regimen for non‐muscle‐invasive bladder cancer. Previously, patients who experienced recurrences after BCG therapy tended to be lumped together as patients with ‘BCG failure’, but BCG failure was defined inconsistently in each study and several studies indicated that patients with a particular pattern of BCG failure had a worse prognosis.We divided patients with BCG failure into four groups, which were based mainly on the responsiveness to BCG therapy and duration until tumour recurrence. Patients in the BCG‐refractory group, in particular, had a higher risk for subsequent stage progression and disease‐specific death over a long duration compared with patients in the other BCG‐failure groups. As the definitions of BCG failure used to date have been decidedly heterogeneous, we recommend that standardized treatment decisions, protocols and recommendations be established according to individual BCG failure patterns.OBJECTIVE
To investigate the differences in the clinical features and subsequent stage progression and disease‐specific survival among patients with Bacillus Calmette‐Guérin (BCG) failure, after dividing these patients into BCG‐refractory, ‐resistant, ‐relapsing, and ‐intolerant groups.
PATIENTS AND METHODS
We identified 173 patients with initial BCG failure from 521 patients who had undergone induction BCG therapy for non‐muscle‐invasive bladder cancer, excluding CIS, between 1987 and 2009.
Patients were stratified into four BCG‐failure groups, and each prognostic outcome was evaluated.
RESULTS
Median follow‐up period from initial BCG failure was 4.7 years.
A total of 42 patients (24.3%) were stratified into the BCG‐refractory, three (1.7%) into the BCG‐resistant, 106 (61.3%) into the BCG‐relapsing, and 22 (12.7%) into the BCG‐intolerant group.
Twenty‐four patients (13.9%) experienced stage progression during follow‐up.
Multivariate analysis showed that pathological G3 at BCG failure (P= 0.014; risk ratio 2.84) and BCG‐refractory (P < 0.001; risk ratio 4.68) were independent predictors for stage progression. The 10‐year progression‐free survival rates were 53.2%, 91.1% and 93.8% in the BCG‐refractory, BCG‐relapsing and BCG‐intolerant groups, respectively. The stage progression rate was higher in the BCG‐refractory than in the BCG‐relapsing (P < 0.001) and BCG‐intolerant (P= 0.007) groups.
Similarly, the 10‐year disease‐specific survival rate in the BCG‐refractory group was significantly worse than those in the other BCG failure groups (P < 0.001).
CONCLUSIONS
Stratification of BCG failure into the above‐mentioned four groups can identify patients with BCG‐failure in terms of their prognosis.
The potential risk for critical adverse events was higher in the BCG‐refractory group than in the other BCG‐failure groups, despite the fact that patients in each group all underwent induction BCG therapy, therefore, treatment decisions, protocols and recommendations should be established based on each individual BCG‐failure pattern.