Complete 5-year follow-up of a prospective phase II trial of preoperative chemoradiotherapy for esophageal cancer.

Abstract

Conclusive evidence supporting the routine use of multimodality therapy in esophageal cancer is lacking. However, since long-term survival after esophagectomy alone is unusual, clinical trials designed to identify effective therapeutic regimens are essential. We report here the 5-year results of a phase II induction chemoradiotherapy trial. From August 1991 to January 1995, 44 patients with esophageal or gastroesophageal junction carcinoma were treated with a combination of 5-fluorouracil, cisplatin, and interferon-alpha with concurrent external beam radiotherapy. Forty-one (93%) patients completed chemoradiotherapy, with most toxic events recorded as grade I or II. Curative resection (all gross tumor removed) was achieved in 36 of 37 surgical explorations, with 10 tumors demonstrating complete pathologic response and 23 showing partial pathologic response. Median follow-up for survivors was 75 months (range, 60-100 months). Five-year survival for all patients was 32%, with a median survival of 28 months. Five-year disease-free survival in patients with curative resection was 36% (median, 26 months) and overall survival was 39% (median, 34 months). Five-year survival for patients with curative resection whose disease responded to chemoradiotherapy was 42% (median overall survival, 36 months). Local-regional recurrence alone occurred in 3 patients, distant failure alone in 12 patients, and combined local-regional and distant failure in 2 patients. A Cox proportional hazards model identified both pathologic tumor and nodal stage as independent predictors of disease-free survival. Fourteen patients (32%) were 5-year survivors; 1 of these patients later experienced disease recurrence and died. Preoperative chemoradiotherapy can result in a long-term and durable disease-free state. Only large, multi-institutional phase III trials can determine whether combined modality therapy is superior to resection alone.