Treatment of locoregional esophageal cancer

Since the mid 1970s combined-modality treatment has been investigated for locoregional cancer of the esophagus. Single-institution pilot studies of preoperative cisplatin-based chemotherapy have shown that 40% to 60% of patients with squamous cell carcinoma achieve a partial response, while an occasional patient has a pathologically documented complete response (CR). Two randomized trials involving small numbers of patients have not confirmed the survival benefit for preoperative chemotherapy that some pilot studies suggested. A large, multicenter intergroup trial is in progress, comparing preoperative and postoperative cisplatin/5-fluorouracil chemotherapy with immediate surgery, and includes both squamous cell carcinoma and adenocarcinoma histologies. Preoperative chemoradiotherapy programs have used survival and pathologic CR as end points. Single-institution and multicenter pilot studies have consistently reported pathologic CR in 25% to 30% of patients. Median survivals have varied from 12 to 29 months. The results from multicenter pilot trials are at the lower end of this range, with more encouraging results coming from single institutions. One randomized trial in progress compares a 3-week intensive cisplatin/vinblastine/5-fluorouracil and concurrent radiotherapy regimen followed by surgery with immediate surgery. No completed comparative trials have been published. Chemoradiotherapy without surgery is a more recent approach stimulated both by the poor survival rates with primary surgery and by its associated morbidity and mortality. The results of the intergroup randomized trial of concurrent cisplatin 5-fluorouracil/radiotherapy versus radiotherapy alone have demonstrated a role for chemotherapy. Median survival and 12- and 24-month survival improved significantly with the combined-modality treatment. This treatment program is now recommended for patients with locoregional disease who are not candidates for surgery. The optimal management of patients with esophageal cancer is still unknown. Accurate methods to stage patients clinically and to identify prognostic factors are needed. The randomized trials in progress evaluating preoperative and postoperative chemotherapy and preoperative chemoradiotherapy are essential to move forward with improved treatment strategies.