Hyperthermic Mitomycin C Yields 68% 1-Year HG-RFS in BCG-Unresponsive NMIBC

Hyperthermic intravesical chemotherapy (HIVEC) with mitomycin C produced a 12-month high-grade recurrence-free survival (HG-RFS) rate of 68% in patients with Bacillus Calmette-Guérin (BCG)–unresponsive non–muscle-invasive bladder cancer (NMIBC), according to a news release from Combat Medical, the developer of the Combat bladder recirculation system (BRS) used to deliver the treatment.¹ The retrospective, real-world findings were presented by Yoran L. Tomassen, MD, of Erasmus MC Cancer Institute in Rotterdam, the Netherlands, at the 18th European Multidisciplinary Congress on Urological Cancers (EMUC).²

What were the key efficacy findings with HIVEC?

At 12 and 24 months, HG-RFS rates in the overall cohort were 68% (95% CI, 59%-76%) and 40% (95% CI, 30%-50%), respectively. Outcomes differed by the presence of carcinoma in situ (CIS) at baseline (log-rank P = .043). Among patients with papillary-only disease, HG-RFS rates were 83% (95% CI, 72%-94%) at 12 months and 51% (95% CI, 37%-71%) at 24 months; among those with CIS-containing disease, the respective rates were 61% (95% CI, 51%-73%) and 33% (95% CI, 23%-47%).

In patients with CIS, the 6-month complete response (CR) rate was 56% (n = 35/63; 95% CI, 43%-67%). Among evaluable patients with a CR at 6 months, 68% (n = 17/25; 95% CI, 48%-83%) maintained a CR at 12 months. The progression-free survival (PFS) rates were 92% (95% CI, 87%-97%) at 12 months and 78% (95% CI, 70%-87%) at 24 months.

Joost L. Boormans, MD, PhD, head of urology at Erasmus MC, said in the press release that HIVEC achieved “meaningful cancer control” with a favorable safety profile in this population, supporting its potential as a bladder-preserving option in routine practice.¹

What was the safety profile of HIVEC?

Among all 150 patients, 66% (n = 99/150) experienced at least 1 adverse event (AE), with 150 AEs reported across 1251 instillations, a rate of 12 AEs per 100 instillations. Nearly all AEs (n = 148/150; 99%) were grade 1 or 2; the 2 grade 3 events were urinary tract infections. Four AEs led to treatment discontinuation.

How was the HIVEC study designed?

The retrospective cohort study included 150 patients with BCG-unresponsive NMIBC treated with HIVEC at Erasmus University Medical Center and Amphia Hospital in the Netherlands between 2015 and 2022. Treatment consisted of mitomycin C delivered through the Combat BRS recirculating system for 60 minutes at 41 °C to 43 °C. The primary end points were HG-RFS and CR in patients with CIS; the secondary end points were PFS and AEs.

Most patients were male (82%), and the median age was 74 years (IQR, 66-78). At baseline, 35% of patients had papillary-only disease, 34% had pure CIS, and 31% had papillary disease with CIS. By European Association of Urology risk group, 15% of patients had intermediate-risk disease, 69% had high-risk disease, and 16% had very high–risk disease. Patients received a median of 10 HIVEC instillations (IQR, 6-10), and 138 received at least 5. The median follow-up was 21 months (IQR, 11-44).

The investigators concluded that HIVEC is a reasonably effective and safe bladder-sparing option for patients with BCG-unresponsive NMIBC who decline or are unfit for radical cystectomy, which remains the recommended treatment in this setting.

What is next for HIVEC in BCG-unresponsive NMIBC?

Combat Medical plans to confirm the findings in the prospective HIVEC HEAT trial (ISRCTN49174478). The phase 3, single-arm study is enrolling 238 patients with BCG-unresponsive NMIBC across 25 sites in the United Kingdom, with separate substudies for patients with CIS, with or without papillary disease, and for those with high-grade papillary Ta/T1 disease without CIS.^3,4 Patients will receive 15 treatments over 12 months, each consisting of 80 mg mitomycin C heated to 43 °C and administered over 60 minutes.

References

1. Combat Medical reports 68% high-grade recurrence-free survival at 12 months in BCG-unresponsive non-muscle invasive bladder cancer study. News release. Combat Medical. November 9, 2026. Accessed November 10, 2026. https://tinyurl.com/ys9msz5b
2. Tomassen YL, Stam AW, Boormans JL, van Kessel KEM, Pijpers OM. Hyperthermic intravesical mitomycin C in BCG-unresponsive non-muscle-invasive bladder cancer. Presented at: 18th European Multidisciplinary Congress on Urological Cancers; November 5-8, 2026; Brussels, Belgium.
3. HIVEC® HEAT (Hyperthermic intravesical mitomycin mEdac) for pAtients with BCG-unresponsive nonmuscle-invasive bladder cancer Trial. ISRCTN registry. Updated June 2, 2026. Accessed November 10, 2026. https://tinyurl.com/7pkxb48b
4. Combat Medical highlights patient impact of HIVEC HEAT trial at the American Urological Association Annual Meeting. News release. Combat Medical. May 27, 2026. Accessed November 10, 2026. https://tinyurl.com/yf5dr5pf