The effect of gender on response to bacillus Calmette-Guerin therapy for patients with non-muscle-invasive urothelial carcinoma of the bladder

OBJECTIVE To determine the influence of gender on the outcome of patients with high-risk non-muscle-invasive bladder cancer treated with intravesical bacille Calmette-Guerin (BCG) therapy, as the role of hormone status in the pathogenesis of urothelial carcinoma and the response to treatment remains subject to debate. PATIENTS AND METHODS We reviewed 1021 consecutive patients (756 men and 265 women) who were treated with induction BCG between 1978 and 2006 for multiple or recurrent high-grade Ta, T1, and/or carcinoma in situ (CIS) bladder cancer. All patients had >= 5 years of follow-up. The endpoints of initial response to BCG and the time to disease recurrence and progression were correlated with gender using Kaplan-Meier methods and multivariate Cox regression models. RESULTS Men were significantly more likely to present with high grade (P = 0.003) tumours and with CIS (P < 0.001), while age and clinical stage at presentation were similar between men and women. There was no significant difference in the initial response to BCG by gender, as 593/756 (78.4%) men and 219/265 (82.6%) women had no evidence of disease at 6 months after BCG treatment (P = 0.14). The median time to recurrence after BCG therapy was also similar for men and women (20 vs 21 months, P = 0.51). Likewise, there was no evidence of a significant association between gender and the risk of disease progression after BCG therapy, such that the 5-year estimated freedom from progression was 77% and 82%, respectively, for men and women (P = 0.08). Moreover, on a multivariate analysis controlling for patient age and tumour stage, grade and CIS, gender was not associated with the risk of recurrence (hazard ratio 0.94, 95% confidence interval 0.79-1.11; P = 0.44) or progression (1.18, 0.85-1.63; P = 0.33) after BCG. When the outcomes for women treated with BCG were stratified by age < 50 years (the median age of menopause in the USA) vs >= 50 years, again there were no differences in the risk of tumour recurrence (P = 0.95) or progression (P = 0.35). CONCLUSION These data suggest that the outcomes of men and women with high risk non-muscle-invasive urothelial carcinoma treated with BCG are similar. As such, further studies are required to determine the clinical relevance of preclinical evidence that has suggested a potential role for sex steroids in the pathophysiology of bladder cancer.