Intravesical bacillus Calmette-Guérin (BCG) with and without isoniazid (INH) is associated with outcomes superior to those intravesical epirubicin in patients with intermediate- and high-risk Ta and T1 urothelial bladder cancer.
In a study of 837 patients, instillation of BCG alone or with INH decreased the risk of disease recurrence, distant metastases, overall survival, and disease-specific survival compared with instillation of epirubicin, according to a report in European Urology (2009; published online ahead of print).
Richard J. Sylvester, ScD, of the European Organization for Research and Treatment of Cancer headquarters in Brussels, Belgium, and colleagues randomized 837 patients to receive six week instillations of either BCG alone (281 patients), BCG plus INH (277 patients), or epirubicin (279 patients). After a median follow-up of 9.2 years, 43% of subjects experienced recurrence, 8% progressed to muscle-invasive disease, 6% developed distant metastases, 33% died, and 4.5% died as a result of bladder cancer.
Compared with the epirubicin group, those treated with BCG had a significant 38% decreased risk of recurrence, 45% decreased risk of distant metastases, a 24% decreased risk of all-cause mortality, and a 53% decreased risk of death from bladder cancer. The researchers observed no significant difference in time to progression or in non-bladder cancer mortality.
Among patients with intermediate-risk malignancy, those treated with BCG had a significant 41% decreased risk of recurrence, 58% decreased risk of distant metastases, and 65% decreased of death from bladder cancer compared with those in the epirubicin group, according to researchers.
Among subjects with high-risk disease, BCG treatment was associated with a significant decreased risk of recurrence, 45% decreased risk of distant metastases, 24% decreased risk of all-cause mortality, and 53% decreased risk of death from bladder cancer.
As for why BCG had an apparently larger effect in the intermediate-risk patients, Dr. Sylvester’s group noted that BCG, which is a nonspecific immunotherapy, may be more effective in patients with a lower tumor burden.
With regard to why BCG had a significant risk-lowering effect on distant metastases but not on progression, the authors explained that BCG may have an effect on micrometastases via a systemic immune response. In the intermediate-risk group, BCG appeared to decrease the risk of progression (treatment was associated with a nonsignificant 44% decreased risk), but too few progressions occurred in the BCG-treated patient to make meaningful comparisons, the authors noted.