# High Oncological Efficacy of BCG Maintenance Therapy for Primary High-Grade T1 Urothelial Carcinoma of the Bladder

## TL;DR

BCG maintenance therapy significantly improves outcomes for high-grade bladder cancer but requires dose adjustments due to side effects.

## Contribution

Demonstrates BCG's efficacy in high-risk bladder cancer despite frequent adverse events and dose reductions.

## Key findings

- Maintenance BCG therapy significantly prolonged recurrence-free survival compared to other treatments.
- Tumor multiplicity was identified as an independent risk factor for recurrence.
- Dose reductions did not increase recurrence rates in BCG-treated patients.

## Abstract

High-grade pT1 urothelial carcinoma (HG-T1 UC) is a non-muscle-invasive bladder cancer with a high risk of recurrence and progression. We retrospectively analyzed 204 patients treated at Toho University Sakura Medical Center to evaluate real-world outcomes of intravesical therapies, mainly Bacillus Calmette–Guérin (BCG) and intravesical chemotherapy. Maintenance BCG therapy significantly prolonged recurrence-free survival compared with other treatments, even in very high-risk cases. However, over half of the patients experienced adverse events, and dose reductions were required in approximately 60% of them. These reductions did not increase recurrence rates. Tumor multiplicity was identified as an independent risk factor for recurrence. This study clarifies the efficacy and challenges of BCG maintenance therapy. For the primary treatment of HG-T1 UC of the bladder, intravesical BCG maintenance therapy should be implemented, incorporating flexible dose reductions and treatment interruptions to effectively manage adverse events.

Background: In high-risk non-muscle-invasive bladder cancer (NMIBC), adjuvant therapies, such as intravesical Bacillus Calmette–Guérin (BCG) instillation, are widely employed; however, BCG treatment poses challenges due to potential adverse effects and ongoing supply limitations. This study aimed to evaluate treatment patterns, therapeutic efficacy, incidence of adverse events, and clinical predictors of recurrence and progression in patients with high-grade pT1 urothelial carcinoma (HG-T1 UC) of the bladder. Methods: This retrospective cohort study included 204 patients diagnosed with HG-pT1 UC who underwent transurethral resection of bladder tumor (TURBT) at Toho University Sakura Medical Center between 2010 and 2021. Clinical data encompassing treatment modalities (BCG or intravesical chemotherapy), complications, and oncological outcomes were collected. Recurrence-Free Survival (RFS), Progression-Free Survival, and Cancer-Specific Survival were analyzed using Kaplan–Meier analyses and multivariate regression models. Results: Maintenance BCG therapy was significantly associated with prolonged RFS compared to other treatments, including among ‘very high-risk’ patients. However, 52.4% of patients receiving BCG maintenance experienced adverse events, with dose reductions required in 59% of cases. Notably, recurrence rates did not significantly differ based on dose reduction or the total number of BCG instillations. Tumor multiplicity emerged as an independent risk factor for recurrence. Conclusions: Although maintenance BCG therapy remains essential for managing HG-T1 UC, especially in high-risk patients, treatment should be individualized due to concerns about tolerability and availability. The study results support the importance of personalized strategies based on risk stratification as outlined in clinical guidelines for preventing recurrence in NMIBC.