Chemohypertheramia with Mitomycin C and COMBAT System in High Risk Non-Muscle Invasive Bladder Cancer: A New Alternative?

Madrid, Spain (UroToday.com)  The recommended treatment for high risk non-muscle invasive bladder cancer after maximal tumor resection with transurethral resection of a bladder tumor (TURBT) is induction with BCG intravesical therapy, accompanied by a maintenance protocol. However, BCG treatment is not devoid of limitations, ranging from major to minor adverse effects, and shortage in supply that was experienced in the not too distant past, leading to a significant disruption in the supply of this treatment to a large proportion of patients.

In this study, the authors present the results of a multicentre European study of high-risk patients treated with Mitomycin C and chemohypertheramia with COMBAT HIVEC™ treatment. This was a retrospective analysis of 145 patients with high risk papillary only non-muscle invasive bladder cancer (NMIBC), treated at 14 centers across Europe between December 2014 to October 2017. High-risk disease was diagnosed according to the European Association of Urology (EAU) risk classification. Following TURBT, all patients were treated with adjuvant intravesical instillations of 40mg MMC at 43°C, for 60 minutes using COMBAT HIVEC™ treatment. All patients received chemohypertheramia treatment because BCG was unavailable at that time, or since the patient could not tolerate BCG because of adverse events. Treatment protocols were decided by individual institutions although most centers provided six weekly instillations of induction with a variable maintenance regime. Whether a restaging TURBT was performed before administering intravesical instillations, was left to the discretion of the clinician and local institutional standard of care. Follow-up entailed cystoscopy every three months on a regular basis.

A total of 145 patients were treated with the COMBAT system with a median follow up of 20.8 months. The mean age of patients was 70.6 years. In 65% of patients the primary tumor was pT1, and in 66% the tumor was graded as G3. Of all patients, 46% had multiple tumors, and 36% were larger than 3cm. Overall, 80% of the patients managed to receive a minimum of 6 weekly instillations as part of induction therapy. However, only 55% of the patients received some form of maintenance therapy. In the intention to treat analysis (145 pts), the mean follow-up period was only 21 months, and the recurrence-free rate was 82%, while the progression-free rate to T2 disease was 98%. In contrast, in the per-protocol analysis (at least six instillations, 116 patients), the mean follow-up period was 22 months, and the recurrence-free rate was 83%, while the progression-free rate to T2 disease was 93%. Importantly, the recurrence-free rate at the one-year follow-up was 87.3%.

The authors conclude that chemohypertheramia entailing six weekly induction 40 mg Mitomycin C intravesical instillations using the COMBAT system, is a viable alternative to intravesical BCG therapy. Importantly, the recurrence-free and progression-free rates at one-year follow-up were like those shown in the EORTC nomograms. The major limitations of this study include its retrospective nature and a relatively small cohort of patients. Furthermore, there was no control group to compare the results to. For us to definitively ascertain that chemohypertheramia is a truly equal and alternative therapy to BCG, randomized controlled double-blind studies are required. 

Presented by: Villacampa Felipe, Madrid, Spain