Bladder-sparing Treatment in Patients with Bacillus Calmette-Guerin–unresponsive Non–muscle-invasive Bladder Cancer: An Analysis of Long-term Survival Outcomes

Background: Data for bladder-sparing treatment (BST) in bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer (NMIBC) patients report short-term outcomes limited to 1–2 yr. Objective: To assess long-term survival outcomes of BCG-unresponsive NMIBC patients treated with BST. Design, setting, and participants: BCG-unresponsive NMIBC patients diagnosed between January 2000 and September 2021 from an institutional NMIBC registry were evaluated. Intervention: Long-term survival outcomes for patients receiving BST, early radical cystectomy (RC), and delayed RC were compared. Outcome measurements and statistical analysis: The primary endpoints were overall survival (OS) and cancer-specific survival (CSS). Results and limitations: In total, 114 patients with a median follow-up of 71.2 mo (interquartile range: 32.6–132.2) were analyzed. There were no significant differences in OS (hazard ratio [HR]: 1.40, 95% confidence interval [CI]: 0.68–2.89, p = 0.4) or CSS (HR: 0.88, 95% CI: 0.22–3.55, p = 0.9) between patients undergoing early RC (n = 38) and BST (n = 76). At 60 mo, BST patients had a high-grade recurrence-free rate, muscle-invasive disease/metastasis progression-free rate, and avoidance of RC rate of 37%, 83%, and 58%, respectively. Current smoker status (HR: 4.44, 95% CI: 1.41–13.97, p = 0.011) was the only variable predictive of high-grade recurrence following a multivariable analysis. The median time to RC from BCG-unresponsive date was 2.1 and 11.7 mo for those undergoing early RC and delayed RC (after BST), respectively. Patients treated with early RC had a higher incidence of cT1 disease (53% vs 36%, p = 0.049) and lymphovascular invasion (LVI; 11% vs 0%, p = 0.011) compared to patients treated with BST. Survival outcomes were similar between groups: 10-yr OS—58% versus 50% (HR: 1.40, 95% CI: 0.68–2.89, p = 0.4), and 10-yr CSS—81% versus 85% (HR: 0.88, 95% CI: 0.22–3.55, p = 0.9). Conclusions: An analysis of long-term survival of BCG-unresponsive NMIBC patients receiving BST suggests that it may be safe in patients without LVI and/or variant histology and nonsmokers. Survival outcomes for patients treated with BST may not be inferior to those receiving early RC. Patient summary: Bladder-sparing treatment can be offered to appropriately selected patients who have bacillus Calmette-Guerin (BCG)-unresponsive non–muscle-invasive bladder cancer. Long-term outcomes may not be inferior to those for patients who opt for early radical cystectomy.