Preoperative chemoradiotherapy has been shown to improve survival among patients with esophageal or esophagogastric-junction cancer, supporting the role of neoadjuvant treatment for those with potentially curable disease, according to a study published May 31 in the New England Journal of Medicine.

In addition to survival benefits, chemoradiotherapy was associated with few high-grade toxic effects and could be administered as an outpatient treatment, according to Pieter van Hagen, MD, of Erasmus University Medical Center, Rotterdam, the Netherlands, and colleagues.

“With new diagnoses in more than 480,000 patients annually, esophageal cancer is the eighth most common cancer worldwide. It is a highly lethal disease, causing more than 400,000 deaths per year,” wrote the authors, who added that a quarter of the patients treated with primary surgery have microscopically positive resection margins, with a five-year survival rate of 40 percent or less.

To compare the benefit of the two treatment strategies, the researchers randomized patients with resectable tumors to receive either neoadjuvant chemoradiotherapy followed by surgery or surgery alone. A total of 366 patients, enrolled March 2004 through December 2008, were included in the analysis, 75 percent of whom had adenocarcinoma, 23 percent of whom had squamous-cell carcinoma and 2 percent of whom had large-cell undifferentiated carcinoma.

Results showed that complete resection, with no tumor within 1 mm of the resection margins, was achieved in 92 percent of patients who received preoperative chemoradiotherapy, compared with 69 percent in the surgery-only group. Complete remission was achieved in 29 percent of those who underwent resection after chemoradiotherapy, who also had a median overall survival of 49.4 months; median survival in the surgery-only group was 24 months. This translated into a 34 percent lower risk of death for patients treated with neoadjuvant chemoradiotherapy followed by surgery.

“The difference in overall survival in the present study is not due to poor survival in the surgery group but can clearly be attributed to improved survival in the chemoradiotherapy–surgery group,” summed the authors, who noted that survival among the surgery-only group was better than previous research had demonstrated, likely due to gradual improvements in surgical techniques, patient selection and staging methods.

With regard to adverse side effects, leukopenia was the most common hematologic toxic effect in the chemoradiotherapy group, occurring in 6 percent of patients, followed by neutropenia in 2 percent of patients. The most common major nonhematologic toxic effects were anorexia and fatigue, occurring in 5 percent and 3 percent of patients, respectively.

There was a higher rate of complete remission among patients with squamous-cell carcinoma compared with patients with adenocarcinoma, but van Hagen and colleagues pointed out that histologic tumor type was not a prognostic factor for survival. “That is, patients with adenocarcinoma and patients with squamous-cell carcinoma both benefited from neoadjuvant chemoradiotherapy.”