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

Objectives: 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.

Patients And Methods: 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.

Results: 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.

Conclusions: 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.