Radiation With Neoadjuvant Chemotherapy Does Not Improve Outcomes in Esophageal Squamous Cell Cancer

Neoadjuvant treatment improves survival for patients undergoing esophagectomy for esophageal cancer. Recent evidence suggests that neoadjuvant chemoradiation offers no advantage over chemotherapy alone before surgical resection for adenocarcinoma histology. We sought to examine if this applies to patients with squamous cell histology.

The National Cancer Database was queried for patients who underwent treatment for squamous cell carcinoma of the esophagus from 2004 to 2012. Patients who underwent neoadjuvant chemotherapy before esophagectomy were compared with those undergoing chemotherapy and radiation before surgical resection. Associations between potential covariates and treatment were analyzed using the Pearson chi-square test for categorical variables and Wilcoxon rank sum test for continuous variables. Univariate and multivariate proportional hazards modeling results were used to assess the effect of treatment on overall survival. Relative prognosis was summarized using estimates and 95% confidence limits for the hazard ratio. Unadjusted differences in overall survival and disease-specific survival between the treatment are shown using Kaplan-Meier methods.

A total of 902 patients underwent neoadjuvant therapy before surgical resection during the study period, with 827 receiving chemotherapy and radiation, and 75 receiving chemotherapy alone preoperatively. The 30- and 90-d mortality for patients undergoing neoadjuvant chemotherapy and radiation followed by surgery were 5.4% and 10.4% compared to 5.5% and 11.1% for patients who received chemotherapy alone preoperatively (P = 0.963 and P = 0.856), respectively. Median overall survival for patients receiving chemotherapy and radiation was 36.0 mo versus 40.8 mo for chemotherapy alone. The 5-y survival was 39% for the chemotherapy and radiation group and 43% for the chemotherapy group (logrank P = 0.7212).

For patients undergoing neoadjuvant treatment before planned surgical resection of squamous cell carcinoma of the esophagus, the addition of radiation to neoadjuvant chemotherapy did not improve long-term survival and did not appear to impact short-term outcomes postoperatively. Further study with a randomized phase III trial is needed.