Long‐term outcomes of a randomized controlled trial comparing thermochemotherapy with mitomycin‐C alone as adjuvant treatment for non‐muscle‐invasive bladder cancer (NMIBC)
Authors: Colombo Renzo , Salonia Andrea , Leib Zvi , Pavone‐Macaluso Michele , Engelstein Dov 
Published: October 2010

Study Type – Therapy (RCT) Level of Evidence 1b

What’s known on the subject? and What does the study add?

Microwave‐induced hyperthermia and mitomycin C is a device‐assisted approach used to treat non‐muscle invasive bladder cancer (NMIBC) either in the adjuvant (prophylactic) set‐up or in an ablative regimen. Until recently, around 20 different studies have been published with data on the short term results of treatment. Previous prospective randomized studies showed the superiority of the chemo‐hyperthermia regimen when compared to intravesical chemotherapy alone in terms of recurrence‐free survival in intermediate and high‐risk NMIBC patients at minimum 24‐month follow‐up. The current study confirmed the result also in long‐term (minimum 10 years) follow‐up. It also represents one of a few to show such extended follow‐up periods for any intravesical therapy for NMIBC.

OBJECTIVE

• To present long‐term efficacy data of intravesical thermochemotherapy vs chemotherapy alone with mitomycin‐C (MMC) randomly administered to patients with non‐muscle‐invasive bladder cancer (NMIBC) as an adjuvant treatment after complete transurethral resection.

PATIENTS AND METHODS

• In all, 83 patients with intermediate‐/high‐risk NMIBC, following complete transurethral resection, were randomly assigned to receive either intravesical thermochemotherapy by means of Synergo® (Medical Enterprises, Amsterdam, The Netherlands) or intravesical chemotherapy alone, for prophylaxis of tumour recurrence.

• Two doses of MMC (20 mg dissolved in 50 mL distilled water administered throughout two consecutive sessions) was used as the chemotherapeutic agent in both arms.

• In all, 75 patients completed the original study (35 of 42 in the treatment arm, 40 of 41 in the control arm), whose results at minimum 2‐year follow‐up have already been published.

• Recently, the files of these patients have been updated for long‐term outcome definition. Data on general health, follow‐up examinations, tumour relapse or progression, and cause of death were collected and analysed.

RESULTS

• Updated complete data collection was available for 65/75 (87%) of the original patients.

• The median follow‐up for tumour‐free patients was 91 months. The 10‐year disease‐free survival rate for thermochemotherapy and chemotherapy alone were 53% and 15%, respectively (P < 0.001).

• An intent‐to‐treat analysis performed to overcome the potential bias introduced by the asymmetrical discontinuation rate still showed a significant advantage of the active treatment over the control treatment. Bladder preservation rates for thermochemotherapy and chemotherapy alone were 86% and 79%, respectively.

CONCLUSION

• This is the first analysis of long‐term follow‐up of patients treated with intravesical thermochemotherapy. The high rate (53%) of patients who were tumour‐free 10 years after treatment completion, as well as the high rate (86%) of bladder preservation, confirms the efficacy of this adjuvant approach for NMIBC at long‐term follow‐up, even in patients with multiple tumours.