Stage at diagnosis and survival outcomes in esophageal carcinoma: A multicenter real-world study.

Abstract

e16087 Background: Esophageal carcinoma (EC) is a highly lethal malignancy, with prognosis largely dependent on stage at diagnosis. While early-stage disease may be curable, advanced-stage EC is associated with poor survival and high metastatic burden. Contemporary real-world data comparing outcomes by stage remain limited. We aimed to evaluate the impact of stage at diagnosis on survival and distant metastatic risk in a large global cohort. Methods: We conducted a multicenter retrospective cohort study using TriNetX, a federated global database, among adult patients (≥18 years) diagnosed with esophageal carcinoma (EC) between January 1, 2015, and January 9, 2026. Patients were stratified by stage at diagnosis into early- (0–II) and advanced- (III–IV) stage disease. The index date was defined as the first documented diagnosis of EC. Outcomes assessed included all-cause mortality at 6 months, 12 months, and 3 years, as well as the development of distant metastases to the liver, bone, and lung following diagnosis. 1:1 propensity score matching was performed using a nearest-neighbor approach. Outcomes were analyzed using Kaplan–Meier with the log-rank test and hazard ratios (HR) with 95% confidence intervals (CI); p < 0.05 was considered statistically significant. Results: A total of 14,261 patients with EC were identified, including 4,884 with stage 0–II and 9,377 with stage III–IV disease. After propensity score matching, adjusting for age, sex, race, and comorbidities, including hypertension, diabetes mellitus, obesity, prior myocardial infarction, and smoking history, 4,615 patients remained in each cohort. Early-stage disease was associated with significantly improved survival across all time points, with HR 0.38 (95% CI 0.34–0.43) at 6 months, HR 0.38 at 12 months (95% CI 0.35–0.42), and HR 0.40 (95% CI 0.37–0.43) at 3 years compared to those with advanced-stage disease. Moreover, advanced-stage disease was associated with a significantly higher incidence of liver metastases (HR 0.25, 95% CI 0.21–0.29) and bone metastases (HR 0.25, 95% CI 0.20–0.30). No statistically significant difference was observed in lung metastases between cohorts (HR 0.87; 95% CI 0.73–1.04). Conclusions: In this large real-world analysis, early-stage esophageal carcinoma was associated with substantially improved short- and long-term survival compared with advanced-stage disease. Advanced-stage EC demonstrated a significantly higher risk of liver and bone metastases, highlighting the systemic progression characteristic of later stages. These findings underscore the critical importance of early detection and timely intervention to improve outcomes in esophageal carcinoma.