Nonregional Lymph Nodes as the Only Metastatic Site in Stage IV Esophageal Cancer

Introduction: Metastatic involvement of at least one nonregional lymph node currently renders patients with esophageal cancer as having stage IV disease. However, the management and outcomes of patients whose sole determinant of stage IV status is nonregional lymph nodes (abbreviated as “stage IV-nodal” disease) have not been fully characterized. Methods: In this retrospective cohort study, the National Cancer Database was queried to identify patients 18 years of age or older who were diagnosed with stage IV esophageal cancer between 2016 and 2019. Survival was assessed by Kaplan-Meier analysis and Cox models in the overall sample and a propensity-matched sample. Patients with “stage IV-nodal” disease were compared with patients with systemic metastases involving a single organ or multiple organs. Results: Overall, 11,589 patients with clinical stage IV esophageal cancer were identified, including 1331 (11.5%) patients with stage IV-nodal disease. Patients with stage IV-nodal disease were more likely to receive chemotherapy (77%) than those with single systemic organ metastases (64%) and multiorgan metastases (63%) (p < 0.0001); patients with stage IV-nodal disease were also more likely to receive radiation (49%) than those with single systemic organ metastases (40%) and multiorgan metastases (39%) (p < 0.0001). Squamous cell carcinoma (OR = 1.58, 95% confidence interval [CI]: 1.34–1.86, p < 0.0001) and academic facility type (OR = 1.24, 95% CI: 1.09–1.4, p = 0.0009) were associated with higher likelihood of the stage IV-nodal presentation. Patients with stage IV-nodal disease experienced superior survival (hazard ratio = 0.72, 95% CI: 0.66–0.78, p < 0.0001) than those with stage IV-single systemic metastases (reference group) and stage IV-multiorgan disease (hazard ratio = 1.30, 95% CI: 1.24–1.37). Conclusions: Approximately 12% of patients with stage IV esophageal cancer lack systemic metastases at presentation. These patients with stage IV-nodal disease are more likely to receive treatment and experience superior survival. Further study of the stage IV-nodal population and consideration of a potential stage IV subclassification system is justified.