Recirculating hyperthermic intravesical chemotherapy with mitomycin C (HIVEC) versus BCG in high-risk non-muscle-invasive bladder cancer: results of the HIVEC-HR randomized clinical trial

PURPOSE: The purpose of the study was to compare the outcomes of high-risk non-muscle-invasive bladder cancer (HR-NMIBC) patients treated with BCG vs recirculating hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C (MMC). METHODS: A pilot phase II randomized clinical trial was conducted including HR-NMIBC patients, excluding carcinoma in situ. Patients were randomized 1:1 to receive intravesical BCG for 1 year (once weekly for 6 weeks plus subsequent maintenance) or HIVEC with 40 mg MMC, administered using the Combat BRS system (once weekly instillations were given for 6 weeks, followed by once monthly instillation for 6 months). Total recirculating dwell time for HIVEC was 60 min at a target temperature of 43° ± 0.5 °C. Primary endpoint was recurrence-free survival. Secondary endpoints were time to recurrence, progression-free survival, cancer-specific survival, and overall survival at 24 months. Adverse events were routinely assessed. RESULTS: Fifty patients were enrolled. Mean age was 73.5 years. Median follow-up was 33.7 months. Recurrence-free survival at 24 months was 86.5% for HIVEC and 71.8% for BCG (p = 0.184) in the intention-to-treat analysis and 95.0% for HIVEC and 75.1% for BCG (p = 0.064) in the per protocol analysis. Time to recurrence was 21.5 and 16.1 months for HIVEC and BCG, respectively. Progression-free survival for HIVEC vs BCG was 95.7% vs 71.8% (p = 0.043) in the intention-to-treat analysis and 100% vs 75.1% (p = 0.018) in the per protocol analysis, respectively. Cancer-specific survival at 24 months was 100% for both groups and overall survival was 91.5% for HIVEC vs 81.8% for BCG. CONCLUSION: HIVEC provides comparable safety and efficacy to BCG and is a reasonable alternative during BCG shortages. TRIAL REGISTRATION: EudraCT 2016-001186-85. Date of registration: 17 March 2016. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00345-022-03928-1.