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

Hyperthermic intravesical chemotherapy using epirubicin showed encouraging oncological results when given after bacillus Calmette-Guérin (BCG) failure and appears to be a potential treatment alternative in a first-line setting when BCG is not available or contraindicated. 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. 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. 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. 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. 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.