A randomized trial of radical cystectomy versus radical cystectomy plus cisplatin, vinblastine and methotrexate chemotherapy for muscle invasive bladder cancer

Purpose: Standard treatment for muscle invasive transitional cell cancer of the bladder is radical cystectomy. Despite careful staging, the majority of cancers with regional lymph node involvement and/or invasion to adjacent organs eventually recur. We investigated the benefit of chemotherapy with cisplatin, methotrexate and vinblastine (CMV) after radical cystectomy. Materials and Methods: A prospective trial was done in which patients were randomized after cystectomy to receive either 4 cycles of CMV chemotherapy or observation. At relapse, patients were treated with standard CMV chemotherapy for metastatic disease at our institution. Results: Of 55 patients who entered this trial 1 was ineligible and in 4 it is too soon to be evaluated. Of the 50 evaluable patients 25 were randomized to receive adjuvant CMV chemotherapy and 25 were observed. In the CMV arm 12 (48%) and in the observation arm 5 (25%) never had recurrence. With a median followup of 62 months and no patient with less than 2 years of followup, the freedom from progression in the adjuvant chemotherapy group was superior to that in the observation group (median 37 versus 12 months, respectively, p = 0.01). Median survival in the adjuvant group was 63 months compared to 36 months for the observation group. Surprisingly, some cases with relapse could be salvaged with CMV chemotherapy, perhaps contributing to this lack of difference in overall survival (p = 0.32). Conclusions: Treatment with CMV chemotherapy after radical cystectomy is an acceptable approach in patients with stages p3b and p4NO or N1 transitional cell carcinoma of the bladder. Further studies must be performed to determine whether these results can be extrapolated to patients with more limited disease (stages p2 and p3a) who are currently treated with radical cystectomy or definitive irradiation.