Long-term oncologic outcomes of epirubicin-based hyperthermic intravesical chemotherapy in BCG-naive patients with non-muscle-invasive bladder cancer: A multicenter retrospective observational study

Abstract

Introduction: Non-muscle-invasive bladder cancer (NMIBC) accounts for approximately 75% of bladder cancer cases and demonstrates substantial variability in recurrence and progression. Bacillus Calmette-Guérin (BCG) is the recommended adjuvant intravesical therapy in intermediate- and high-risk tumors; however, shortages and contraindications necessitate alternative treatments. Hyperthermic intravesical chemotherapy (HIVEC) has been mainly studied with mitomycin C, and data on epirubicin-based HIVEC are limited.

Objective: This study evaluated first-line epirubicin-based HIVEC in BCG-naive patients with NMIBC.

Methods: In this study, we included and retrospectively analyzed BCG-naive patients from our prospectively recorded, multicenter HIVEC database who received HIVEC in a first-line setting between March 2017 and September 2022. Treatment included six weekly induction instillations followed by six monthly maintenance instillations. The primary outcome was recurrence-free survival (RFS), while secondary outcomes included progression-free survival, extravesical RFS, disease-free survival, cancer-specific survival, and the need for radical cystectomy.

Results: Twenty-three patients with intermediate-, high-, or very high-risk NMIBC received epirubicin-based HIVEC in a first-line setting. The median follow-up was 35 months (IQR 29-52). Two patients (8.7%) experienced intravesical recurrence (both carcinoma in situ). Median RFS was 35 months (IQR 26-50), with 1- and 2-year RFS rates of 100.0% and 95.6%, respectively. No patient experienced progression, extravesical recurrence, cancer-specific death, or required radical cystectomy.

Conclusion: First-line epirubicin-based HIVEC in BCG-naive patients provided durable oncological control in predominantly high- and very high-risk NMIBC. These results indicate that epirubicin-based HIVEC may represent a potential alternative when BCG is unavailable or contraindicated. However, the small sample size and observational design limit interpretability, underscoring the need for larger randomized trials to clarify the role of epirubicin-based HIVEC in this setting.

Keywords

Bladder cancer / Non-muscle-invasive bladder cancer / Bacillus Calmette- Guérin-naive / Hyperthermic intravesical chemotherapy / Epirubicin / Progression / Recurrence / Cystectomy

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