Long-term results of neoadjuvant treatment with M-VAC (methotrexate, vinblastine, doxorubicin, and cisplatin) for locally invasive transitional cell carcinoma of the urothelium

Background. Cisplatin-based combination chemotherapy has been widely used in patients with advanced urothelial cancer; however, it remains unclear whether this therapy improves survival. The aim of this study was to evaluate the long-term results of neoadjuvant methotrexate, vinblastine, doxorubicin, and cisplatin (M-VAC) treatment in patients with locally invasive transitional cell carcinoma of the urothelium. Methods. Between January 1989 and March 1993, 32 patients with clinical stage T2-4 urothelial cancer received neoadjuvant M-VAC followed by total cystectomy and/or nephroureterectomy. We retrospectively analyzed the long-term results of this therapy, and examined the pathological findings in relation to clinical outcome. Results. Thirteen of 29 evaluable patients (44.8%) demonstrated a clinical response. At a median follow-up of 71 months of the 32 patients, 18 (56.2%) were alive without evidence of recurrent disease, 12 (37.5%) had died of metastatic and/or recurrent disease, and 2 (6.3%) had died of other diseases. The 5-year cause-specific survival rates were: 66.9% for all patients, 90.0% for patients with a major pathological response (stage pT0, pTis, or pT1), and 55.0% for those with no pathological response (stage pT2 or more) (P < 0.05); and 81.8% for patients without lymph node metastases (pN0) and 25.4% for those with lymph node metastases (pN1 or more) (P < 0.05). There was no significant difference in survival rates between clinical responders and nonresponders. Conclusions. These findings revealed that pathological stage and lymph node involvement, rather than clinical response, were well correlated with the prognosis of patients with invasive urothelial cancer who received neoadjuvant M-VAC.