Oncological Outcomes of Epirubicin-based Hyperthermic Intravesical Chemotherapy in Bacillus Calmette-Guérin (BCG)-naïve Patients and Patients with BCG Failure: A Multicenter Retrospective Observational Study

Background and objective: Intravesical instillation of bacillus Calmette-Guérin (BCG) is the standard therapy for patients with intermediate-risk or high-risk non-muscle-invasive bladder cancer. In cases of BCG failure, device-assisted hyperthermic intravesical chemotherapy (HIVEC) using epirubicin can be offered to patients who are unfit for or decline radical cystectomy. The aim of this study was to investigate long-term oncological outcomes for patients treated with HIVEC in a first-line or second-line setting. Methods: We retrospectively analyzed our prospective database of patients who underwent HIVEC with epirubicin between November 2016 and December 2024 at two Swiss university centers. Survival was assessed using Kaplan-Meier curves and log-rank tests. Cox regression models were used to explore associations between clinicopathological variables and time-to-event outcomes. Key findings and limitations: Of the 88 patients included, 23 (26.1%) received HIVEC as first-line treatment and 65 (73.9%) after BCG failure. Median follow-up was 38 mo (interquartile range 22-54). Intravesical recurrence was observed in 26 patients (29.6%), with 1-yr and 2-yr intravesical recurrence-free survival rates of 84.1% and 77.3%, respectively. Extravesical recurrence in the upper urinary tract or prostatic urethra occurred in 21 patients (23.9%). Progression to muscle-invasive or metastatic disease due to intravesical recurrence was observed in eight patients (9.1%), with 1-yr and 2-yr progression-free survival rates of 96.6% and 93.2%, respectively. Conclusions and clinical implications: Device-assisted epirubicin-based HIVEC yielded encouraging long-term oncological outcomes both for first-line therapy and after BCG failure. Extravesical recurrences were observed at a relatively high rate in the group with BCG failure, which highlights the importance of monitoring for extravesical disease in future studies and follow-up planning. Prospective studies are needed to confirm the efficacy of epirubicin-based HIVEC, particularly in first-line settings. Patient summary: We tested in-bladder treatment with a heated solution of a chemotherapy drug for patients with recurrence of non-muscle-invasive bladder cancer after failure of BCG (bacillus Calmette-Guérin) therapy. Our results show promising cancer control rates after BCG failure, and suggest that this treatment may also be a valuable option when BCG is unavailable and in patients for whom BCG is not suitable.