Pathological Regression of Lymph Nodes Better Predicts Long-term Survival in Esophageal Cancer Patients Undergoing Neoadjuvant Chemotherapy Followed by Surgery

Objective: To evaluate pathological response to NAC in metastatic LNs, and assess its clinical prognostic significance in patients with EC. Summary of Background Data: The pathological response to preoperative treatment is commonly evaluated in the PT. However, LN metastases strongly correlate with systemic micro-metastases. Thus, pathological evaluation of LN response could more accurately predict prognosis in EC patients undergoing NAC before surgery. Methods: We enrolled 371 consecutive patients who underwent triplet NAC followed by surgery for EC between January 2010 and December 2016. Pathological LN regression grade was defined by the proportion of viable tumor area within the whole tumor bed area for all metastatic LNs: grade I, >50%; II, 10%–50%; III, <10%; and IV, 0%. We analyzed the correlation of grade with clinico-pathological parameters. Results: Among 319 patients with clinically positive LNs, pathological LN regression grades were I/II/III/IV in 115/51/58/95 patients, and 191 patients (59.9%) showed discordance between the PT and LN pathological regression grades. LN regression grade significantly correlated with cN positive number, ypTNM, lymphovascular invasion, and clinical/pathological PT response. Multivariate analysis for recurrence-free survival revealed that LN regression grade [hazard ratio (HR) = 2.25, P < 0.001], ypT (HR = 1.65, P = 0.005), and ypT (HR = 1.62, P = 0.004) were independent prognostic factors, but not pathological PT regression grade (P = 0.67). Conclusions: Compared to PT response, pathological LN response better predicted long-term survival in EC patients who received NAC plus curative surgery.