Treatment and survival in patients with recurrent high-risk non-muscle-invasive bladder cancer

Background: Multiple recurrences develop in patients with high-risk non-muscle-invasive bladder cancer. As neither the association of recurrences with survival nor the subsequent aggressive treatment in individuals with recurrent high-grade non-muscle-invasive bladder cancer has ever been quantified, we sought to determine whether the increasing number of recurrences is associated with higher subsequent treatment and mortality rates. Methods: Using linked Surveillance, Epidemiology, and End Results-Medicare data, we identified subjects with recurrent high-grade, non-muscle-invasive disease diagnosed in 1992 to 2002 and followed up until 2007. Using competing-risks regression analyses, we quantified the incidence of radical cystectomy, radiotherapy, and systemic chemotherapy after each recurrence. We then performed a propensity-score adjusted competing-risks regression analysis to determine whether the increasing recurrences portend worse survival. Results: Of 4,521 subjects, 2,694 (59.6%) had multiple recurrences within 2 years of diagnosis. Compared with patients who only had 1 recurrence, those with≥4 recurrences were less likely to undergo radical cystectomy (hazard ratio [HR] = 0.73, 95% CI: 0.58-0.92), yet more likely to undergo radiotherapy (HR = 1.51, 95% CI: 1.23-1.85) and systemic chemotherapy (HR = 1.58, 95% CI: 1.15-2.18). For patients with≥4 recurrences, only 25% were treated with curative intent. The 10-year cancer-specific mortality rates were 6.9%, 9.7%, 13.7%, and 15.7% for those with 1, 2, 3, and≥4 recurrences, respectively. Conclusions: Only 25% of patients with high-risk non-muscle-invasive bladder cancer who experienced recurrences at least 4 times underwent radical cystectomy or radiotherapy. Despite portending worse outcomes, increasing recurrences do not necessarily translate into higher treatment rates.