Assessing the Impact of Treatment Timing Protocols in Clinical Trials for Bacillus Calmette-Guérin-unresponsive Non-muscle-invasive Bladder Cancer.

Abstract

Patients with bacillus Calmette-Guérin (BCG)-unresponsive (UR) non-muscle-invasive bladder cancer (NMIBC) who are ineligible for or decline radical cystectomy may pursue bladder-sparing therapy (BST). Currently, most BST trials in the BCG-UR setting mandate treatment initiation within 60-90 d of histopathologic confirmation. Given the lack of data on optimal treatment windows, we evaluated whether these time restrictions have oncologic merit. We retrospectively reviewed data for patients with BCG-UR NMIBC treated with BST at a tertiary referral center. Commonly used clinical trial cutoffs for time to treatment were assessed using Kaplan-Meier analysis. Multivariable Cox regression analysis was also performed, with time to treatment included as a continuous variable. Progression-free survival (PFS) was the primary endpoint, defined as progression to muscle-invasive disease or metastasis. Similar PFS was observed when using 30-d, 60-d, and 90-d cutoffs (all p > 0.05). These results were corroborated on multivariable analysis with adjustment for BST type. Secondary endpoints, including cystectomy-free survival and overall survival, were comparable across time-to-treatment intervals (all p > 0.05), with findings supported by multivariable analyses. These results indicate that inclusion criteria based on time to treatment can probably be expanded, which would allow more patients to participate in clinical trials by avoiding leadtime exclusion.