A randomized prospective study of intravesical prophylaxis in non-musle invasive bladder cancer at intermediate risk of recurrence: mitomycin chemotherapy vs BCG immunotherapy

OBJECTIVE: The present study compared the therapeutic activity of intravesical BCG with intravesical mitomycin C chemotherapy in patients with non-muscle invasive bladder cancer at intermediate risk of recurrence in a prospective randomised trial. METHODS: 96 patients with low grade recurrent non-muscle invasive bladder cancer (Ta or T1) were randomly assigned to intravesical treatment with BCG or mitomycin C. RESULTS: The follow up ranged from 12 to 108 months (mean 65.7+/-25.6 months). Half of the patients were free of recurrence respectively after mitomycin C (23/46) and BCG (23/46) treatment. Recurrences after BCG presented in the first 6 month period (> 50%) or in the long term follow up (> 3 years) whereas early (< 6 months) or long term (> 3 years) recurrences after MMC treatment were less frequent. Time to recurrence in the MMC arm was 17.5+/-15.4 and in the BCG arm 21.9+/-24.8 (p = 0.47). None progressed to muscle-invasive tumour or underwent cystectomy during the observation period. MMC caused grade 1-2 toxicity in 11 patients (mild or moderate cystitis in 6 and mild or moderate hypersensitivity reactions in 5) and grade 3 toxicity in 11 patients (severe cystitis in 4, gross haematuria in 2 and severe hypersensitivity in 5 cases). Nineteen of the BCG treated patients had grade 1-2 toxicity (mild to moderate cystitis or prostatitis in 17, mild fever and myalgia in 2) and 3 developed grade 3 toxicity (severe cystitis in 2 patients and epididymitis that led to the necessity of antituberculous therapy in one patient). Intravesical treatment was discontinued in 11 patients under MMC treatment and in 2 patients under BCG treatment (p = 0.008). CONCLUSIONS: Both MMC and BCG demonstrate efficacy in prolonging the time to recurrence with respect to the period of observation before treatment, so reducing the hospitalisation rate for TUR of the recurrent tumours, but no difference in the recurrence rates was observed between MMC and BCG as primary treatment. A significant number of patients treated with MMC suffered cystitis or hypersensitivity reactions so severe to cause discontinuation of the treatment. The vast majority of patients treated with BCG had only mild or moderate side effects under BCG treatment but a serious infection was observed in one case requiring antituberculous treatment