Real-world Outcomes of Chemoradiotherapy with or Without Surgery in Locally Advanced Esophageal Cancer: A Retrospective Analysis

squamous cell carcinoma (SCC) and adenocarcinoma (AC)differ in geographic distribution, risk factors, and response to treatment, with SCC predominating in developing regions and AC rising sharply in Western populations (2,3).In Jordan, the Jordan Cancer Registry documented a steady increase in gastrointestinal malignancies between 2000 and 2013, driven by demographic growth, rising life expectancy, AbstractObjectives: The management of locally advanced esophageal cancer (EC) has evolved considerably, with neoadjuvant chemoradiotherapy (nCRT) followed by surgery remaining the standard of care for eligible patients, and definitive chemoradiotherapy serving as an alternative for those who are medically unfit or who decline surgery.Real-world data from the Middle East are scarce.This study evaluates treatment outcomes at King Hussein Cancer Center (KHCC).Methods: This single-center retrospective cohort study included all patients with locally advanced EC treated with curative-intent chemoradiotherapy at KHCC between 2014 and 2023.A broader institutional cohort was used to contextualize radiotherapy utilization over time.Survival endpoints-overall survival (OS), local control (LC), progression-free survival (PFS), and distant metastasis-free survival (DMFS)-were estimated by Kaplan-Meier analysis.Multivariable Cox regression with backward Akaike information criterion-based selection was performed.Results: Fifty-four patients were analyzed.The median age was 59.5 years (range, 24-83), and 80.6% were male.Adenocarcinoma accounted for 74.1% and squamous cell carcinoma for 25.9% of cases.Tumors were predominantly located in the lower esophagus (79.6%).Surgery was performed in 24 patients (44.4%); of these, 95.8% achieved R0 resection and 16.7% attained a pathologic complete response.Median follow-up was 59.0 months.Median OS was 31.0 months; 12-, 24-, and 48-month OS rates were 84.8%, 66.2%, and 36.5%,respectively.The 48-month LC, PFS, and DMFS rates were 67.2%, 29.5%, and 28.5%, respectively.On multivariable analysis, surgery was significantly associated with improved LC [hazard ratio (HR) 0.18, 95% confidence interval (CI) 0.04-0.83,p=0.03] and OS (HR 0.37, 95% CI 0.16-0.89,p=0.03).At the institutional level, radiotherapy utilization increased over time (OR per year 1.16, p=0.062). Conclusion:In this real-world cohort, surgical resection following nCRT was associated with improved LC and OS.Definitive CRT provided meaningful disease control in carefully selected patients, particularly those unfit for surgery.These findings support multidisciplinary decision-making and warrant prospective validation to refine selection criteria for non-operative strategies.