Effectiveness of Chemotherapy With/Without Radiotherapy for Locally Advanced Esophageal Squamous Cell Carcinoma: A Population-based Target Trial Emulation Study

Background/Aim: The utility of neoadjuvant radiotherapy for patients with locally advanced esophageal squamous cell carcinoma (LA-ESCC) receiving preoperative systemic treatment remains a subject of ongoing debate. Patients and Methods: In this population-based cohort study, we screened for LA-ESCC cases diagnosed over 2011-2022 using data from the Taiwan Cancer Registry. We utilized the target trial emulation (TTE) framework, employing propensity score weighting (PSW) to mitigate the effects of observed confounding variables. We then compared the hazard ratio (HR) of death between the neoadjuvant concurrent chemoradiotherapy (nCCRT) group and the neoadjuvant chemotherapy (nCT) group. Additionally, a comprehensive assessment of other outcomes and extensive supplementary analyses were performed. Results: The primary analysis included 2069 patients. Overall survival was not significantly different between the nCCRT and nCT groups, with a PSW-adjusted HR of 0.82 (95% confidence interval=0.52-1.28; p=0.62). Similar results were found for other endpoints, although the pathological complete response rate was higher in the nCCRT group. The results remained similar in the supplementary analyses. Conclusion: In this population-based TTE study, the overall survival of LA-ESCC patients treated with nCCRT was not significantly different from that of patients treated with nCT.