Prognostic relevance of lymph node regression on survival in esophageal cancer: a systematic review and meta-analysis

INTRODUCTION: The prognostic value of histomorphologic regression in primary esophageal cancer has been previously established, however the impact of lymph node (LN) response on survival still remains unclear. The aim of this review was to assess the prognostic significance of LN regression or downstaging following neoadjuvant therapy for esophageal cancer. METHODS: An electronic search was performed to identify articles evaluating LN regression or downstaging after neoadjuvant therapy. Random effects meta-analyses were performed to assess the influence of regression in the LNs and nodal downstaging on overall survival. Histomorphologic tumor regression in LNs was defined by the absence of viable cells or degree of fibrosis on histopathologic examination. Downstaged LNs were defined as pN0 nodes by the tumor, node, and metastasis classification, which were positive prior to treatment neoadjuvant. RESULTS: Eight articles were included, three of which assessed tumor regression (number of patients = 292) and five assessed downstaging (number of patients = 1368). Complete tumor regression (average rate of 29.1%) in the LNs was associated with improved survival, although not statistically significant (hazard ratio [HR] = 0.52, 95% confidence interval [CI] = 0.26–1.06; P = 0.17). LNs downstaging (average rate of 32.2%) was associated with improved survival compared to node positivity after neoadjuvant treatment (HR = 0.41, 95%CI = 0.22–0.77; P = 0.005). DISCUSSION: The findings of this meta-analysis have shown a survival benefit in patients with LN downstaging and are suggestive for considering LN downstaging to ypN0 as an additional prognostic marker in staging and in the comparative evaluation of differing neoadjuvant regimens in clinical trials. No statistically significant effect of histopathologic regression in the LNs on long-term survival was seen.