Update on the Dutch Cooperative Trial: mitomycin versus bacillus Calmette-Guérin-Tice versus bacillus Calmette-Guérin RIVM in the treatment of patients with pTA-pT1 papillary carcinoma and carcinoma in situ of the urinary bladder. Dutch South East Cooperative Urological Group. Intravesical chemotherapy (mitomycin C) versus immunotherapy (bacillus Calmette-Guérin) in superficial bladder cancer.
Prophylactic intravesical treatment with chemotherapeutic agents or one of the different strains of the immunomodulator bacillus Calmette-Guérin (BCG) reduces tumor recurrence and may prevent progression after transurethral resection (TUR) of superficial bladder cancer. Clinical and pathological prognostic factors are used to categorize different groups at risk for disease recurrence and progression. Solitary low-grade (G1, 2A), low-stage (pTa) tumors have less than a 5% risk of progression, while pT1 G3 tumors with concomitant carcinoma in situ (CIS) have a considerably higher risk of progression and metastases. Thus, prospective clinical trials should consider the different risks associated with different prognostic groups and stratify patients accordingly. The Dutch Cooperative Trial evaluated mitomycin versus BCG-Tice versus BCG-RIVM in 469 patients with pTA/pT1 carcinoma and CIS of the urinary bladder after TUR. Of 437 evaluable patients, 50 had CIS, 254 had pTA tumors, and 133 had pT1 tumors. No statistical differences were observed in toxicity between the two strains of BCG, but local and systemic side effects were more frequent in the BCG groups versus the mitomycin group. No differences in response rate were observed between the 3 treatment groups in patients with CIS. A statistically significant difference in favor of mitomycin was seen, however, in patients with papillary tumors. Mitomycin and BCG-RIVM were equally effective, and mitomycin proved significantly more effective than BCG-Tice. No significant difference in efficacy was observed between the two strains of BCG. Disease recurrence during the study in patients with papillary tumors was seen in 43% of mitomycin-treated patients, 64% of the BCG-Tice group, and 46% of patients treated with BCG-Rivm. However, a subgroup analysis for time to first recurrence for pTa versus pT1 and for grade 1 and 2 versus grade 3 papillary tumors showed no statistically significant between-group difference. Further studies comparing identical regimens, doses, and patient groups are needed to define more clearly which patient groups and tumors are more likely to respond to intravesical therapy. Both intravesical mitomycin C (MMC) and bacillus Calmette-Guérin (BCG; Pasteur strain F) were effective in the present prospective randomized multicenter study consisting of 91 patients with frequently recurrent superficial (Ta-T1) bladder cancer. The result was in favour of BCG, as shown by the measurements with complete response (CR), disease-free interval and recurrence rate. CR of 58% with MMC and 40% with BCG were reached in 22 instillation series on carcinoma in situ of 18 patients. Due to side effects, MMC instillations were discontinued in 8.6%, and BCG instillations in 19.6%, respectively. After the 2-year follow-up also 1 case of pulmonary tuberculosis occurred in the BCG group.