Complete long-term survival data from a trial of adjuvant chemotherapy vs control after radical cystectomy for locally advanced bladder cancer.

To report the long-term follow-up of patients with locally advanced bladder cancer treated with either adjuvant combined chemotherapy with methotrexate, vinblastine, doxorubicin/epirubicin, and cisplatin (MVAC/MVEC) or no additional treatment after radical cystectomy, to examine various survival endpoints and factors associated with long-term survival. Between May 1987 and December 1990, 49 patients undergoing radical cystectomy for locally advanced bladder cancer were randomized to observation only or adjuvant systemic chemotherapy with three cycles of MVAC/MVEC (methotrexate 30 mg/m(2) on day 1, 15 and 22; vinblastine 3 mg/m(2) on day 2, 15 and 22; doxorubicin 30 mg/m(2) or epirubicin 45 mg/m(2) on day 2; and cisplatin 70 mg/m(2) on day 2 of a 28-day cycle). Data were obtained for progression-free, overall and tumour-specific survival. In all, 23 patients were randomized to the control arm and 26 to treatment with adjuvant chemotherapy. The trial intended to accrue 100 patients but was stopped after an interim analysis showed a marked difference in progression free-survival when these first 49 patients had been randomized. The intent-to-treat analysis, including hazard ratios (HR) with 95% confidence intervals and point estimates at 10 years for control vs adjuvant chemotherapy, was as follows: progression-free survival HR 2.84 (1.46-5.54; P= 0.002), 13.0% vs 43.7%; overall survival HR 1.75 (0.95-3.23; P= 0.069), 17.4% vs 26.9%; and tumour-specific survival HR 2.52 (1.28-4.99; P= 0.007), 17.4% vs 41.7%, respectively. The long-term results further support the use of adjuvant-combined chemotherapy with cisplatin-based regimens after radical cystectomy for locally advanced bladder cancer, as this significantly improves progression-free and tumour-specific survival.