BCG vs Chemohyperthermia with Mitomycin C for High-Risk Non-Muscle Invasive Bladder Carcinoma: Preliminary Results of HIVEC-HR Randomized Clinical Trial

Madrid, Spain (UroToday.com) The shortage of Bacillus Calmette–Guérin (BCG) intravesical instillations that occurred several years ago resulted in the expedited search for alternative therapeutic options for a patient with non-muscle invasive bladder cancer (NMIBC).

The HIVEC-HR is a pilot study aiming to compare the efficacy and safety of BCG and chemohyperthermia with mitomycin C. In this poster, the authors presented their preliminary results.

The HIVEC-HR is a randomized, open pilot clinical trial, recruiting patients with high-risk NMIBC according to the European Association of Urology (EAU) Guidelines. Exclusion criteria included the presence of carcinoma in situ (CIS), and patients with any kind of inability, for any reason, to undergo BCG or MMC treatments.

Patients were randomly assigned in a 1:1 ratio to one of the following groups:

  • BCG (TICE strain): 50 mg diluted in 50 mL of sterile saline, held for 2 hours in the bladder, one weekly instillation for six weeks and maintenance according to the SWOG protocol.
  • Chemohypertheramia: 40 mg Mitomycin C diluted in 40 mL of distilled water at 43ºC using COMBAT® recirculation system for 60 minutes, once weekly instillation for six weeks and then once monthly instillation for six months.
The follow-up protocol entailed cytology and cystoscopy every three months in addition to upper urinary tract imaging on a yearly basis, according to the recommendations by the EAU Guidelines. The primary endpoint was recurrence-free survival at 24 months. Secondary objectives included safety, progression rate, overall survival and quality of life.

 The results demonstrated that fifty patients had been randomized (100% recruitment completed). Median age was 74 years, 87% were males, and 85% had primary tumors. Baseline characteristics were comparable in both groups, and median follow-up was10.5 months from TURBT completion.

For the BCG group, two recurrences and one progression to T2 were reported, and only one recurrence and no progressions happened in the Chemohypertheramia group.

Regarding safety profile, the adverse event rate was similar in both groups (8 in the BCG group and 7 in the chemohypertheramia group). However, the BCG associated adverse effects were more severe. Additionally, three instillations were postponed in this group due to adverse events (Figure 1). Four patients in each group discontinued treatment due to these adverse events.

UroToday 3rd Bladder Congress different adverse events in the BCG and the chemohyperthemia groups
Figure 1 – Comparison of the different adverse events in the BCG and the chemohyperthemia  groups:

The authors concluded that chemohypertheramia in high-risk NMIBC patients seems at least as effective as BCG regarding efficacy. Lastly, chemohyperthermia has a better safety profile and tolerability than BCG.  This study is limited by the small number of patients, the fact that it is a single center institution study. Longer follow-up data is required with a larger number of patient to determine whether chemohypertheramia is truly equivalent to BCG.


Presented by: Guerrero-Ramos Felix, Madrid, Spain