Outcomes of Patients with Bacillus Calmette-Guérin (BCG)-Unresponsive Non-Muscle Invasive Bladder Cancer as Defined by the U.S. Food and Drug Administration

Abstract

Background: Limited data are available on the outcomes of patients with non-muscle invasive bladder cancer (NMIBC) unresponsive to intravesical bacillus Calmette-Guérin (BCG), as defined by the United States Food and Drug Administration.

Objective: To define the outcomes of patients with BCG-unresponsive NMIBC.

Methods: This was a retrospective, single-institution observational cohort study. Records of patients managed at our institution for BCG-unresponsive NMIBC between 2005 and 2020 were reviewed and clinical outcomes evaluated.

Results: The study included 149 patients. Management was with initial radical cystectomy in 60 patients (40%) and initial bladder-sparing therapy (BST) in 89 patients (60%). Overall survival was greater among patients undergoing RC than BST (HR 1.83, 95% CI 1.04-3.22, p = 0.036), potentially due to patient selection, as no significant difference was noted for metastasis-free or cancer-specific survival. Patients opting for initial BST had high rates of treatment failure, with estimated 5-year cystectomy-free survival of only 42%. Patients who received additional lines of BST after a subsequent failure were at increased risk of having ≥pT3 or pN+ disease at cystectomy (42% for ≥2 lines BST, versus 18% for 1 line BST and 15% for initial cystectomy, p = 0.038).

Conclusion: Among patients who underwent initial BST for BCG-unresponsive NMIBC, rates of treatment failure were very high. Patients who underwent delayed cystectomy after ≥2 lines of BST had elevated rates of extravesical disease. Our observations emphasize the importance of recent and ongoing clinical trials in this clinical space.

Keywords: Non-muscle invasive bladder cancer; bacillus Calmette-Guérin; bladder conserving treatment; radical cystectomy.

Fig. 1

Patients included in the study. “Inadequate” BCG was defined as less than 5/6 doses of an induction or reinduction course and less than 2/3 doses of a maintenance course. Abbreviations: BCG, bacille Calmette-Guérin; MIBC, muscle-invasive bladder cancer; NMIBC, non-muscle invasive bladder cancer; UTUC, upper tract urothelial carcinoma; XRT, radiation therapy.

Fig. 2

Oncologic outcomes of patients with BCG-unresponsive NMIBC. Kaplan-Meier curves showing metastasis-free (A), cancer-specific (B) and overall survival (C) of patients with BCG-unresponsive NMIBC opting for either upfront cystectomy or initial bladder-sparing management at the time of BCG unresponsive disease (“BCG failure”). Metastasis-free and cancer-specific survival did not differ significantly between the two groups (HR for MFS 1.30, 95% CI 0.68–2.52, p = 0.42; HR for CSS 1.58, 95% CI 0.78–3.19, p = 0.20), whereas overall survival was greater among patients undergoing initial RC (HR 1.83, 95% CI 1.04–3.22, p = 0.036). Abbreviations: BCG, bacillus Calmette-Guérin; CI, confidence interval; CSS, cancer-specific survival; HR, hazard ratio; MFS, metastasis-free survival; NMIBC, non-muscle invasive bladder cancer; OS, overall survival.

Fig. 3

Oncologic outcomes of patients undergoing bladder-sparing treatment for BCG-unresponsive NMIBC. Kaplan-Meier curves showing recurrence-free (A), progression-free (B), cystectomy-free (C), and bladder-intact metastasis-free survival (D) of patients opting for initial bladder-sparing management of BCG-unresponsive NMIBC. Recurrence-free survival was a composite of high-grade intravesical and systemic recurrence. Progression-free survival was a composite of muscle-invasive (≥T2) and metastatic (nodal/distant) progression. A large majority of patients experienced disease recurrence within the first two years, and over half underwent radical cystectomy within five years of initial BCG failure. Abbreviations: BCG, bacillus Calmette-Guérin; NMIBC, non-muscle invasive bladder cancer.