A Phase II Open-label Randomized Controlled Trial of Adjuvant Chemohyperthermia in Patients with Bladder Cancer - Expert Commentary

Patients with intermediate-risk non-muscle invasive bladder cancer (NMIBC) frequently require adjuvant therapy. The HIVEC-II study is a multi-center randomized controlled trial (RCT) that compared clinical outcomes of intermediate-risk NMIBC patients receiving hyperthermia and mitomycin C versus mitomycin C alone.

The study cohort included 252 patients, 127 in the chemohyperthermia (with mitomycin C) group and 125 in the control (mitomycin C) group from 15 clinical sites in the United Kingdom enrolled between 2014 and 2017. By 24 months, 32% of patients in the chemohyperthermia arm and 38% in the control arm experienced disease recurrence. A per-protocol analysis revealed that the disease-free survival rate at 24 months was higher in the chemohyperthermia group relative to the control, but the difference was not statistically significant.

After adjuvant treatment, 8% of chemohyperthermia patients and 12% of control patients experienced disease recurrence at 3 months. Disease-free survival was 99% in the chemohyperthermia arm and 98% in the control arm at this time point. Eight patients in the chemohyperthermia arm and four in the control arm died during follow-up without disease progression. Patients in the chemohyperthermia group were more likely to exhibit disease progression, although progression-free survival was similar in a per-protocol analysis. Moreover, patients receiving chemohyperthermia treatment were less likely to complete their treatment than patients in the control group. The most common reasons included equipment issues, bladder spasms or urgency, and allergic reactions. The fewer cases of non-compliance in the control group were related to allergic reactions, causes unrelated to treatment, and bladder spasms or urgency. Throughout the study, 632 adverse events were recorded. Of these, 212 events in the chemohyperthermia group and 145 events in the control group were treatment related. Only 20 major adverse events (grade III) were reported in 11 chemohyperthermia patients and five control patients. The most common adverse events were urinary tract pain, hematuria, urinary urgency, and rash.

These findings showed no significant difference in disease-free survival between patients receiving chemohyperthermia compared to room temperature mitomycin C alone.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

  1. Tan WS, Prendergast A, Ackerman C, et al. Adjuvant Intravesical Chemohyperthermia Versus Passive Chemotherapy in Patients with Intermediate-risk Non-muscle-invasive Bladder Cancer (HIVEC-II): A Phase 2, Open-label, Randomised Controlled Trial [published online ahead of print, 2022 Aug 20]. Eur Urol. 2022;S0302-2838(22)02552-0. doi:10.1016/j.eururo.2022.08.003

Read the Abstract