Background: The prognostic value of histomorphologic regression in primary gastric and gastroesophageal cancers (GC/GEJ) has been previously established, however, the impact of lymph node (LN) regression on survival still remains unclear.

Methods: A prospectively maintained database was reviewed to identify cT4N+ gastric and gastroesophageal cancers (GC/GEJ) after NAC (neoadjuvant chemotherapy). Patients were categorized into two groups based on LN status: cN+/ypN0 (downstaged N0) and cN+/ypN+ (persistent N+), long-term survival were analyzed using Kaplan-Meier survival estimates.

Results: In total, 125 patients with cT4N+ GC/GEJ underwent NAC followed by surgery were enrolled. A total of 39 patients (31.2%) had cN+/ypN0 (ypN0) disease, 86 patients (68.8%) had cN+/ypN+ (ypN+) disease. Prognosis in ypN+ patients was significantly worse than those in ypN0 group for 3- and 5-year overall survival (OS) (p < 0.05). The 3-year OS was 83%, 44% in ypN0 and ypN+ group, respectively. The 5-year OS was 75%, 35% in ypN0 and ypN+ group, respectively. Multivariable analysis suggested that multivisceral resection (hazard ratio [HR] = 0.33, 95% confidence interval [CI]: 0.14-0.76, p = 0.009), and ypN+ (HR = 3.42, 95% CI: 1.15-10.13, p =0.027) were independent prognostic factors for OS.

Conclusion: Nodal downstaging is an important hallmark representing the effectiveness of NAC for GC/GEJ, and it positively impacts on survival of these patients.

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