Abstract
BACKGROUND: In esophageal cancer, the ypN0 status after induction therapy could be categorized into two primary groups: "natural N0" (cN0/ypN0) and "down-staged N0" (cN+/ypN0). The assessment of cN status is typically based on clinical imagination or pathological regression. However, there is no standardized method for evaluating cN/ypN status. This study aims to investigate the prognosis of patients with cN+/ypN0 using both assessment methods through a cohort study and meta-analysis. METHODS: A prospectively maintained database encompassing esophageal cancer patients undergoing induction therapy followed by radical esophagectomy was comprehensively reviewed. The prognostic significance of cN+/ypN0 across two evaluation methods was quantified. Additionally, a meta-analysis using data from previous studies was conducted. RESULTS: 578 patients were identified from the cohort analysis, with 342 classified as ypN0 and 236 as ypN+. When evaluated with clinical imagination, patients with cN+/ypN0 had survival outcomes comparable to those with natural N0 but significantly better than those with ypN+ (p < 0.001). Using pathological nodal regression, cN+/ypN0 patients showed superior overall survival compared to ypN+ patients (p = 0.0043), although their disease-free survival was notably inferior to that of natural N0 patients (p = 0.0088). A meta-analysis of 20 previous studies confirmed the prognostic value of cN+/ypN0 status in both clinical imagination and pathological regression. CONCLUSIONS: For esophageal cancer patients receiving neoadjuvant, cN+/ypN0 status, assessed through both clinical imagination and pathological regression, serves as a significant prognostic factor. It holds precedence over ypN+ yet falls short of the natural N0. The pre-treatment categorizations warrant recognition as a novel and pertinent staging metric.