Introduction:

Increasingly, evidence suggests that patients may safely trial a bladder-sparing therapy (BST) following a Bacillus Calmette-Guerin (BCG) unresponsive (UR) high-grade (HG) non-muscle-invasive bladder cancer (NMIBC) diagnosis. Most patients ultimately fail first-line BST (FL-BST), but continue to attempt additional lines of therapy. With the exception of a post-hoc analysis of the KEYNOTE-057 trial, the practice patterns and outcomes surrounding sequential lines of BST following trial of a first-line salvage agent are largely unknown, particularly in the real world setting. Accordingly, the present study aimed to elucidate this unknown.

Methods:

Following IRB approval, a retrospective review of consecutive patients with BCG UR disease treated with BST(s) at Moffitt Cancer Center between 2013 and 2023 was conducted. BCG UR disease was defined in accordance to the 2018 FDA guidance. BSTs were defined as the non-extirpative treatments a patient received following BCG UR diagnosis. Clinicopathologic data was collected, including histopathological features at the time of BCG UR diagnosis, BST(s) treatment history, and survival outcomes. For analysis, two groups were assessed: those receiving only FL-BST and those receiving additional lines of salvage treatment BST (SL-BST+). The primary endpoints were progression free survival (PFS) from metastatic or muscle invasive bladder cancer, and overall survival (OS). Survival estimates were computed using Kaplan Meier (KM) analysis and compared using the log-rank test. Statistical analysis was performed using R (version 2023.06.0+421) with significance set at 0.05.

Results:

126 patients with BCG UR NMIBC who were treated with one or more lines of BSTs were identified. Table 1 outlines the clinicodemographic data. Overall, patients were mostly male (86.5) with a median age of 72.0 years (Interquartile Range [IQR]: 64.8-77.6) and median follow-up of 35.6 months (IQR: 20.9-57.4). Table 2 summarizes the number of patients receiving a given type of BST for each line of therapy. 73 patients received a FL-BST. Of the SL-BST+ patients, 53 pursued salvage second line treatment, 19 pursued salvage third line treatment, six pursued salvage fourth line treatment, and three pursued salvage fifth line treatment. Patients receiving a salvage line of therapy after the 2018 FDA guidance were less frequently treated with rescue BCG (p=0.05). On KM analysis, there were no differences in PFS (Figure 1A; p=0.96) or OS (Figure 1B; p=0.6) between FL-BST and SL-BST+ groups.

Conclusion:

The present study presents real world practice patterns and outcomes for patients pursuing one versus two or more lines of BST after BCG unresponsive diagnosis. No differences in PFS or OS were documented between groups. Cautiously, this suggests that for many patients a trial of an additional BST following nonresponse to first line therapy may not compromise oncologic outcomes. Validation of this finding with a larger cohort would provide rationale for clinical trials that offer SL-BST+ after failure of currently approved agents.

Funding: N/A