Hyperthermic vs normothermic mitomycin C for intermediate-risk NMIBC: a real-world retrospective cohort study

Introduction: Hyperthermic intravesical chemotherapy (HIVeC) with mitomycin C (MMC) is an emerging strategy in the management of intermediate-risk non-muscle-invasive bladder cancer (Ir-NMIBC). By combining chemotherapy with controlled hyperthermia (43°C), this approach aims to enhance drug absorption, increase cytotoxicity, and stimulate immune activation, potentially improving efficacy compared to standard MMC. The aim of this study was to compare oncologic efficacy, adverse effects, and safety between HIVeC and standard normothermic MMC in patients with Ir-NMIBC.
Patients and methods: we conducted a retrospective cohort study including 76 patients with Ir-NMIBC treated between January 2020 and december 2023. Patients received HIVeC (n=36) or standard MMC (n=40) following complete transurethral resection of bladder tumor (TUrBT). The instillation schedule consisted of four weekly induction instillations followed by three monthly maintenance instillations. The primary endpoint was recurrence-free survival (rFs); secondary endpoints included progression-free survival (PFs), adverse events (Aes), and treatment compliance.
Results: A total of 76 patients were included: 36 received HIVeC and 40 received standard MMC. Baseline characteristics were balanced across groups, with a median age of 68 years and 86.8% male. Most tumors were unifocal (85.5%), stage pTa (88.2%), and low-grade (61.8%). At a median follow-up of 36 months (IQr 24-36), recurrence occurred in 38.9% of HIVeC patients vs 30.0% in the MMC group. Median time to recurrence was longer with HIVeC (15.0 vs 10.5 months). The 24-months recurrence-free survival was 62.2% for HIVeC and 69.4% for MMC (p=0.365). Progression to muscle-invasive disease occurred in one MMC patient (2.5%); none progressed in the HIVeC arm (PFs at 24 months: 100% vs 97.5%, p=0.343). Compliance was high in both arms (HIVeC 88.9%, MMC 87.5%). Adverse events were mild (grade 1-2) and evenly distributed; no grade ≥3 events were observed. Treatment discontinuation due to toxicity occurred in 13% of HIVeC and 7% of MMC patients (p=0.47).
Conclusions: HIVeC with MMC demonstrated comparable oncologic outcomes to normothermic MMC in Ir-NMIBC, with a longer time to recurrence and similar tolerability. These findings suggest its potential use in selected patients, but should be interpreted with caution due to the retrospective design and limited sample size.