Effect of Nodal Status Compared to Tumor Response after Neoadjuvant Radiation on Outcomes for Patients with Esophageal Cancer

Introduction: The Dutch CROSS trial established the role of neoadjuvant chemoradiotherapy for improved survival in the treatment of patients with advanced esophageal adenocarcinomas. Both surgery and radiation therapy represent means of loco-regional control, and esophageal cancer is disease that is associated primarily with systemic failure. The goal of the current study is assess the clinico-pathological features of patients with resected esophageal cancer undergoing neoadjuvant radiation therapy on long-term survival. 

Methods: All patients at a single institution who underwent esophagectomy for esophageal adenocarcinoma after neoadjuvant radiation therapy from January 2004 to December 2014 were included. Patients were divided into short-term survivors (STS) who died of disease-specific causes within 1 year of resection and long-term survivors (LTS) who lived in excess of 5 years after surgery. Peri-operative deaths were excluded. Logistic regression analysis was performed to identify factors predicting LTS. 

Results: Of the 334 patients who underwent esophagectomy for adenocarcinoma after neoadjuvant radiation, there were 74 (22.2%) STS and 28 (8.4%) LTS. STS were older (median age 65.5 vs. 56.6 years, P=0.003) and were more likely to have lymph node metastases prior to radiation (93.2% vs. 39.3%, P<0.0001) than LTS. LTS had a trend towards having a complete pathologic response to radiation (46.4% vs. 27.0%, P=0.10), undergoing an open operation (92.9% vs. 77.0%, P=0.09), and having a shorter post-operative length of stay (median 8.5 vs. 11.5 days, P=0.10). Univariable and multivariable analyses are shown in the Table. Only the absence of lymph node metastases on the initial evaluation correlated with LTS (P=0.04), whereas pathologic complete response to neoadjuvant radiation did not (P=0.18). 

Conclusion: Response to neoadjuvant radiation therapy in patients with esophageal cancer does not correlate to survival. Presence of pre-treatment lymph node metastases is likely a marker of systemic disease and is the only variable that predicts outcome with patients with esophageal adenocarcinoma. Clinical response to radiation therapy should not dictate decision for esophagectomy.