Chemoradiotherapy Before Surgery May Improve Survival for Esophageal Cancer

Preoperative chemoradiotherapy improved survival among patients with resectable esophageal or esophagogastric-junction cancer with acceptable adverse events. The findings were reported in the New England Journal of Medicine [2012;366(22):2074-2084].

In the multicenter, randomized, controlled, phase 3 study, the researchers compared neoadjuvant chemoradiotherapy followed by surgery or with surgery alone in patients with potentially curable esophageal or esophagogastric-junction carcinoma. From March 2004 through December 2008, the researchers enrolled 368 patients with histologically confirmed, potentially curable squamous-cell, adenocarcinoma, or large-cell undifferentiated carcinoma of the esophagus or esophagogastric junction.

Only patients with tumors of the clinical stage T1N1 or T2-3N0-1 and no clinical evidence of metastatic spread, according to the International Union Against Cancer tumor-node-metastasis classification, were enrolled. Patients were age 18 to 75, had a World Health Organization performance status of 2 or lower, and had lost 10% or less of body weight. Patients also had to have adequate hematologic, renal, hepatic, and pulmonary function, as well as no history of other cancer or prior radiotherapy or chemotherapy.

Of the 368 patients, 366 were included in the analysis. In both groups, the median age was 60; 134 of 178 patients (75%) in the chemoradiotherapy-surgery group were men, compared with 152 of 188 patients (81%) in the surgery group. Most patients (75%, n=275) had adenocarcinoma, 23% (n=84) had squamous-cell carcinoma, and 2% (n=7) had large-cell undifferentiated carcinoma. Most tumors were located in the distal esophagus (211 of 366 patients [58%]) or at the esophagogastric junction (in 88 patients [24%]). Patients were randomly assigned to chemoradiotherapy followed by surgery (n=178) or to surgery alone (n=188). The treatment regimen for the preoperative chemoradiotherapy group consisted of weekly administration of carboplatin (doses titrated to achieve an area under the curve of 2 mg per milliliter per minute) and paclitaxel (50 mg per square meter of body-surface area) for 5 weeks and concurrent radiotherapy (41.4 Gy in 23 fractions, 5 days per week). The primary end point was overall survival.

The results showed that median overall survival was 49.4 months in the chemoradiotherapy-surgery group, compared with 24.0 months in the surgery group. Overall survival was significantly better in the chemoradiotherapy-surgery group (hazard ratio, 0.657; 95% confidence interval, 0.495-0.871; P=.003). The respective overall survival rates at 1, 2, 3, and 5 years were higher in the chemoradiotherapy-surgery group, compared with surgery group (82%, 67%, 58%, and 47% vs 70%, 50%, 44%, and 34%, respectively).

The main hematologic adverse effects in the chemoradiotherapy-surgery group were leukopenia (6%) and neutropenia (2%); the most common nonhematologic adverse effects were anorexia (5%) and fatigue (3%). Complete resection with no tumor within 1 mm of the resection margins was achieved by 92% in the chemoradiotherapy-surgery group, compared with 69% in the surgery group (P<.001). Among patients undergoing resection after chemoradiotherapy, a pathological complete response was observed in 47 of 161 patients (29%). A pathological complete response was achieved in 28 of 121 patients with adenocarcinoma (23%) versus 18 of 37 with squamous-cell carcinoma (49%; P=.008). Postoperative complications were similar in the 2 treatment groups, and in-hospital mortality was 4% for each treatment arm. After surgery 4 (2%) patients in the intervention group died within 30 days, compared with 5 (3%) in the surgery group (P=.85).

In conclusion, the researchers said that, “preoperative chemoradiotherapy…is safe and leads to a significant increase in overall survival among patients with adenocarcinoma or squamous-cell carcinoma of the esophagus or esophagogastric junction.”