Abstract

To shed light on the interaction between the American Joint Committee on Cancer (AJCC) T stage and M stage in the determination of the overall survival (OS) and cancer-specific survival (CSS) of esophageal carcinoma patients. Moreover, to confirm our hypothesis that tumors that metastasize to distant sites in the early T stage may reflect a more biologically aggressive disease compared with those that metastasize in more advanced T stages.We performed a retrospective cohort study with patients who were pathologically diagnosed with esophageal cancer between 2004 and 2014 in the surveillance epidemiology and end results (SEER) database. The primary study variables were the T and M stage, as well as their interaction terms. We performed a survival analysis of the interaction terms using unadjusted Kaplan-Meier methods and adjusted Cox proportional hazards models. Furthermore, we performed an exploratory analysis with stratification by histological type, esophageal adenocarcinoma (EAC), and esophageal squamous cell carcinoma (ESCC).Data of 19,078 patients were retrieved from the SEER database. Unadjusted Kaplan-Meier curve indicated that patients with T2 and T3 stage had longer median OS and CSS (3 months and 4 months, respectively) than with T1 stage in distantly metastatic esophageal cancer (M1 stage). Multivariate analysis revealed a significant interaction between the T stage and M stage when determining the OS and CSS of esophageal cancer (P < .001). Using T1M0 as a reference, patients with T1M1 had significantly worse OS and CSS than those with T2M1 and T3M1 stage (P < .001). A similar pattern was also observed among patients with EAC and ESCC.Our analysis suggests that the T1 stage predicts worse survival compared with T2 and T3 stage in distantly metastatic esophageal cancer and might be a surrogate for biologically aggressive disease, indicating that those patients should receive more aggressive treatments. Our findings also encourage researchers to discover new genomic changes in this subset of tumors with the potential to uncover new prognostic markers or drug targets. Further researches on the association between T stage and survival in metastatic esophageal cancer are warranted to validate our findings.

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