AUA 2022: HIVEC-E: Spanish Multicenter Prospective Experience with Recirculant Hyperthermic MMC with Combat BRS HIVEC System

(UroToday.com) The 2022 American Urological Association (AUA) Annual Meeting included a session on non-invasive bladder cancer and a presentation by Dr. Ana Bello discussing results of HIVEC-E, a multicenter prospective experience with recirculant hyperthermic Mitomycin-C (MMC) with the COMBAT® bladder recirculation Hyperthermic IntraVEsical Chemotherapy (HIVEC) system. Intravesical hyperthermia with MMC is used in intermediate risk non muscle invasive bladder cancer (NMIBC) and also in high risk NMIBC due to the BCG shortage. The aim of this study was to analyze real-world data on the long-term outcomes of adjuvant HIVEC with MMC and COMBAT® bladder recirculation system for patients with NMIBC.


This prospective observational trial included patients with NMIBC treated with HIVEC using Combat bladder recirculation system in 9 academic institutions in Spain between 2012-2020. Treatment modalities included in this study were based on weekly induction HIVEC MMC, either alone or followed by monthly maintenance. The number of instillations was variable according to the criteria of the different centres involved, patient risk group, and treatment tolerability. Dr. Bello defined the safety population as those with at least one instillation. They were evaluated according to the number and severity of adverse events. The full analysis set population was defined as those treated with HIVEC- MMC 40 mg in the adjuvant setting after transurethral resection of the bladder, together with baseline data and clinical follow-up. In this population, treatment outcomes (recurrence, progression, overall survival) were evaluated, including only those patients for whom information about cancer risk status and follow-up was available.

The safety population included 592 patients, of whom 406 (68.6%) did not have adverse events and 186 (31.4%) suffered at least one adverse event: 170 (20.7%) were grade 1-2 and 16 (2.7%) grade 3-4. The most frequent adverse events were dysuria (10%), pain (7.1%), urgency (5.7%), rash (4.9%), bladder spasms (3.7%), and hematuria (3.6%). The full analysis set population included 502 patients who received a median number of 8.8±3.3 (range 1-20) instillations. Median follow-up was 24.5±16.5 (range 1-81) months. According to EAU 2020 risk groups, 297 (59.2%) patients were intermediate risk and 205 (40.8%) were high risk.

Five-year recurrence and progression-free survival rates were 50.4% (53.3% for intermediate risk and 47.1% for high risk) and 89.8% (94.0% for intermediate risk and 84.2% for high risk), respectively. Multivariate analysis showed that recurrent tumours (HR- 1.83), duration of HIVEC therapy <4 months (HR 1.72) and high risk group (HR 1.47) were identified as risk factors for recurrence. On the other hand, independent factors for progression were high risk (HR 3.89), recurrent tumours (HR 3.32), and no maintenance therapy (HR 2.37). Factors influencing overall survival were patient age at diagnosis (HR 3.36) and treatment duration (HR 1.82). 

Dr. Bello concluded her presentation discussing results of HIVEC-E with the following take-home messages:

  • HIVEC using bladder recirculation system is effective, safe and well tolerated
  • Longer treatment duration, non-recurrent patients, and intermediate risk disease are predictors of response
  • Monthly adjuvant HIVEC-MMC maintenance decreases the progression rate of NMIBC and should be recommended for all patients

Presented by: Ana Plata Bello, MD, La Laguna-Santa Cruz de Tenerife, Spain

Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Assistant Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2022 American Urological Association (AUA) Annual Meeting, New Orleans, LA, Fri, May 13 – Mon, May 16, 2022.