Intra- and extravesical recurrence after epirubicin-based hyperthermic intravesical chemotherapy (HIVEC) in patients with NMIBC and BCG failure: A multicenter retrospective Observational Study.

BACKGROUND: Guidelines recommend intravesical Bacillus Calmette-Guérin (BCG) as adjuvant therapy for intermediate- and high-risk non-muscle-invasive bladder cancer after transurethral resection. In the event of BCG failure, hyperthermic intravesical chemotherapy (HIVEC) represents a treatment alternative to patients who are surgically inoperable, or decline radical cystectomy. OBJECTIVE: The aim of this study was to evaluate oncological outcomes in patients receiving epirubicin-based HIVEC as a second-line therapeutic approach. METHODS: Retrospective inclusion of patients from our prospectively maintained, multicenter HIVEC database, who underwent HIVEC due to recurrent or persistent high-grade NMIBC following adequate BCG therapy (BCG failure) between November 2016 and December 2024. Survival was evaluated using Kaplan-Meier analysis and log-rank testing. Associations between clinicopathological factors and oncological outcomes were assessed using Cox regression analysis. RESULTS: Sixty-five patients were included. Median follow-up was 38 months (IQR 21-55). Twenty-four patients (36.9%) experienced intravesical recurrence with a median intravesical recurrence-free survival (RFS) of 24 months (IQR 9-45) and 1-/2-year intravesical RFS rates of 77.9% and 64.1%, respectively. Extravesical recurrence was observed in 21 patients (32.3%) with a median extravesical RFS of 22 months (IQR 7-43) and 1-/2-year extravesical RFS rates of 81.3% and 70.9%, respectively. Higher number of recurrences prior to HIVEC were significantly associated with extravesical recurrence in univariate (HR 2.23; 95% CI 1.23-3.87; p=0.019) and multivariate analysis (HR 1.31; 95% CI 1.03-1.67; p=0.027). CONCLUSIONS: Although limited by the relatively small sample size, Epirubicin-based HIVEC demonstrated promising oncological outcomes indicating its potential value as bladder-preserving treatment option after BCG failure. Prospective controlled studies are warranted to further assess the role of epirubicin-based HIVEC in this setting.