Outcomes of Intermediate Risk Non-muscle-invasive Bladder Cancer Receiving Adjuvant Treatment: A Pooled Analysis of Four Randomized Controlled Trials.

BACKGROUND AND OBJECTIVE: Historic prediction models overestimate the risk of recurrence and progression for intermediate risk (IR) non-muscle-invasive bladder cancer (NMIBC). We report outcomes for patients with IR-NMIBC and the appropriateness of surveillance cystoscopy protocol using contemporaneous clinical trials. METHODS: Pooled individual IR-NMIBC patient data from four randomized controlled trials (RCT) were analyzed: HIVEC-II, PHOTO, BOXIT, and CALIBER. Patients with IR-NMIBC underwent complete tumor resection and were recommended to receive 6 weekly instillations of mitomycin C. Kaplan-Meier analyses were performed for oncological endpoints. Noncumulative distribution of recurrence was evaluated to determine the appropriateness of surveillance cystoscopy. KEY FINDING: A total of 578 patients with IR-NMIBC, with a median follow-up of 34 mo (interquartile range: 25-55 mo) were included for analysis. There was no meaningful increase in recurrence from 36 to 60 mo: overall recurrence-free rates at 12, 24, 36, and 60 mo were 73%, 61%, 56%, and 54%, respectively. In the multivariable model, the risk of recurrence was higher in patients with prior recurrences (hazard ratio [HR]: 1.75, 95% confidence interval [CI]: 1.16-2.64, p = 0.008), multifocality (HR: 1.49, 95% CI: 1.13-1.95, p = 0.004), and cancer grade (HR: 1.57, 95% CI: 1.08-2.28, p = 0.018). Grade or stage progression was uncommon (<5%), and cancer-specific survival (CSS) was 99% at 60 mo. The noncumulative risk of recurrences at 36 and 60 mo were 17% and <5%, respectively. CONCLUSIONS AND CLINICAL IMPLICATIONS: Patients with IR-NMIBC have a high recurrent risk within 36 mo, but grade/stage progression remains low. Patients could consider terminating/reducing the frequency of cystoscopy after 60 mo because of a low risk of subsequent recurrence.