Sex Remains Negative Prognostic Factor in Contemporary Cohort of High-Risk Non-Muscle-Invasive Bladder Cancer

SIMPLE SUMMARY: Bladder cancer remains the most common malignancy of urinary tract. Sex-related divergent outcomes in bladder cancer have been reported with controversial results. The aim of this multicenter, retrospective study was to assess sex-related diversities in clinical outcomes in patients diagnosed with primary non-muscle-invasive high-risk bladder cancer. In our study, females diagnosed with high-risk non-muscle-invasive bladder cancer had higher risk of disease recurrence when compared to their male counterparts, although the outcomes of men and women subjected to a second restaging transurethral resection of the bladder tumor (reTUR) and treated with adequate Bacillus Calmette–Guérin (BCG) are similar. ABSTRACT: Sex-specific differences in outcomes of patients diagnosed with high-risk non-muscle-invasive bladder cancer (HR-NMIBC) have been reported with controversial findings. This study aims to investigate sex-specific diversities in the treatment and oncologic outcomes of primary HR-NMIBC in a multicenter setting. A multicenter retrospective analysis of 519 patients (388 men and 131 women) treated with transurethral resection (TUR) for primary HR-NMIBC was performed. Univariable and multivariable Cox regression models were used to investigate the association of clinico-pathologic features and generate hazard ratios (HRs). Second-look TUR (reTUR) was performed in 406 (78%) patients. A total of 218 (42%) of patients were subjected to an induction course of intravesical BCG (Bacillus Calmette–Guérin) plus maintenance therapy. The median follow-up was 44 months. Among the entire cohort, 238 (46%) and 86 patients (17%) had recurred and progressed to muscle-invasive disease (MIBC), respectively. Female sex was associated with increased risk of disease recurrence in the entire cohort: HR = 1.94, 95% CI = 1.48–2.55, p < 0.001 and HR = 1.91, 95% CI = 1.39–2.60, p < 0.001 in univariate and multivariate analysis, respectively. In patients subjected to reTUR and treated additionally with BCG, female sex was associated with increased risk of disease recurrence in univariate analysis (HR 1.81, 95% CI 1.07–3.06, p = 0.03), but not in multivariate analysis (HR 1.99, 95% CI 0.98–4.02, p = 0.06). There was no difference between sexes with regard to disease progression. HR-NMIBC diagnosed in females is associated with higher risk of disease recurrence when compared to males.