Real World Multi-Institutional Outcomes of Bladder Carbogen and Nicotinamide (BCON) in Muscle-Invasive Bladder Cancer (MIBC).

Abstract

Bladder carbogen and nicotinamide (BCON), combined with radiotherapy, is a standard of care in the bladder-preserving treatment of muscle-invasive bladder cancer (MIBC). UK national guidelines recommend neoadjuvant chemotherapy (NAC) before bladder preservation. However, patients did not receive NAC in the definitive phase III BCON trial. This study assessed tolerability and real-world outcomes of BCON alone or with NAC (NAC-BCON). With institutional approval, demographics and clinical information were obtained for a retrospective cohort study of BCON patients (2017-2021) across 3 UK centers. Clinician-reported toxicity was assessed using RTOG grading during radiotherapy, 6 weeks and 12 months after. Cross-sectional imaging and cystoscopy determined local control, metastasis-free survival (MFS), and cancer-specific survival (CSS). Subgroup differences were compared using T and χ2 tests. Survival was analyzed by Kaplan-Meier, log-rank, and multivariate Cox proportional hazard regression. Statistical analysis was conducted using R version 4.2.1 (R Core Team (2022)). A total of 317 patients were treated with BCON; 75 (24%) received NAC-BCON. Median follow-up was 29 months (4-63m). Patient characteristics are shown in Table 1. NAC-BCON patients were younger (median 72 vs 78 years, p<0.05), with better PS (p<0.05) and ACE-27 (p<0.05), with no statistical difference in T-staging and histopathology. 298 (94%) completed BCON, whilst 59/75 (79%) completed ≥3 cycles of NAC. There was no significant increased grade 3 acute or late bowel or bladder toxicity with NAC. 3-month cystoscopy post radiotherapy demonstrated complete response in 282/317 (89%). 121 (38%) developed metastases, and 112 (35%) died of MIBC. 5-year BCON MFS was 62% and 49% for NAC-BCON (HR 0.69, 95% CI 0.98- 2.51, p = 0.064); 5-year BCON CSS was 55% and 52% for NAC-BCON (HR 0.83, 95% CI 0.79-1.83, p = 0.39). This remained after adjusting for clinical factors in a multivariate Cox model for both MFS (p = 0.22) and CSS (p = 0.37). Our real-world data compares favorably to published BCON 5-year relapse-free survival (41%) and OS (49%). NAC-BCON has no increased toxicity with comparable treatment completion rates to BCON alone. No significant improvement in survival outcomes was seen with NAC, possibly due to small numbers and patient selection in a non-randomized cohort. Further analysis is planned with additional center input.