A randomized multicenter trial of adjuvant therapy in superficial bladder cancer: transurethral resection only versus transurethral resection plus mitomycin C versus transurethral resection plus bacillus Calmette-Guerin. Participating Clinics. Intravesical administration of bacillus Calmette-Guérin in patients with recurrent superficial carcinoma of the urinary bladder: report of a prospective, randomized trial.
A randomized multicenter trial was done to compare transurethral resection only to transurethral resection plus adjuvant mitomycin C and bacillus Calmette Guerin (BCG) instillation for treatment of superficial bladder cancer (stage pTa/1 grades 1 to 3 except primary stage pTa grade 1).
                Included in the study were 337 patients with superficial stage pTa/1 grades 1 to 3 bladder cancer except primary stage pTa grade 1 tumors. One group underwent transurethral resection alone. Mitomycin C (20 mg./50 ml. sodium chloride) was given every 2 weeks during year 1 and once a month during year 2. BCG (120 mg/50 ml. sodium chloride was instilled once a week for 6 weeks and once a month for 4 months.
                At a median followup of 20.2 months, a decrease in recurrence rate was noted for both drug instillations compared to transurethral resection only. The relative risk of recurrence was 0.508 after mitomycin C and 0.618 after BCG instillation compared to transurethral resection alone. There was no significant difference between the mitomycin C and BCG instillations. The progression rate was comparable in all 3 therapy groups, with an estimated common progression rate of 4.22% per year. Side effects occurred most frequently during or after BCG instillation, most often consisting of cystitis. One patient required cystectomy because of ulcerating cystitis and a prostatic abscess subsequent to unsuccessful tuberculostatic therapy. There were no systemic complications.
                Our study showed a positive effect of adjuvant chemotherapy and immunotherapy on decreasing tumor recurrence rate. No influence was observed concerning progression rate, which was low overall. In an attempt to prevent, delay, or reduce further tumor occurrence, 88 patients with recurrent, superficial carcinoma of the urinary bladder were randomly assigned to receive either standard therapy (cystoscopy with fulguration) or standard therapy and bacillus Calmette-Guérin (BCG). BCG was administered intravesically and percutaneously once weekly for 6 weeks. No serious toxicity was seen. There were 43 evaluable patients in each of the two groups. Results in the BCG group versus the control group were as follows: reduction in the number of recurrent tumors (43 vs 27 patients [P less than 0.001] ); conversion to negative cytology (11 of 33 vs three of 34 patients [P less than 0.05] ); and tumor progression requiring cystectomy (three vs 15 patients [P less than 0.001] ). Disease-free interval (P less than 0.001), time with negative cytology (P less than 0.001), and time to progression of disease (P less than 0.003) were longer in patients treated with BCG. These results indicate that the combination of standard therapy and BCG is more effective than standard therapy alone in patients with recurrent superficial bladder tumors.
In patients with medium/high risk Ta or T1 bladder cancer, immunotherapy with intravesical BCG following TUR appears to provide a significant advantage over TUR alone in delaying tumour recurrence.