Esophageal squamous cell carcinoma (ESCC) is highly prevalent in China, with most patients presenting with locally advanced disease. Neoadjuvant chemoradiotherapy (nCRT) is the current standard of care, while neoadjuvant immunochemotherapy (nICT) has emerged as a promising alternative. However, no large-scale randomized controlled trial has directly compared nICT versus nCRT for long-term overall survival (OS) in this population. This study aims to compare the causal effects of nICT versus nCRT on OS and other key outcomes in patients with resectable locally advanced ESCC using target trial emulation (TTE) methodology. This is a single-center, retrospective, observational cohort study using TTE. Data are derived from electronic health records (EHR) of esophageal cancer patients hospitalized at Henan Cancer Hospital between January 2013 and December 2025. Patients meeting eligibility criteria (age ≥18 years; histologically confirmed ESCC; clinical stage cT3-4a N0-2 M0 or cT2N+ M0; ECOG PS 0-1; no prior antitumor therapy) are assigned to nICT or nCRT groups based on actual treatment initiation. Propensity score overlap weighting is used to balance baseline covariates. The primary outcome is overall survival (OS). Secondary outcomes include event-free survival (EFS), pathological complete response (pCR) rate, tumor regression grade (TRG), R0 resection rate, and safety. This study will provide real-world causal evidence on the comparative effectiveness of nICT versus nCRT in the Chinese ESCC population.
Age ≥ 18 years at the time of diagnosis.
Histologically confirmed esophageal squamous cell carcinoma (ESCC).
Clinical stage cT3-4a N0-2 M0 or cT2N+ M0 (AJCC 8th edition), with no distant metastasis (M1), based on clinical staging records available at Time Zero.
ECOG performance status 0-1 (or proxy: total hospitalization days ≤14 days in the past year if ECOG PS is missing).
Distant metastasis (M1) or clinically determined unresectable disease.
Active concurrent malignancy within 5 years prior to diagnosis (excluding basal cell carcinoma of the skin or carcinoma in situ).
Severe comorbidities significantly limiting life expectancy or precluding neoadjuvant therapy (proxy: total hospitalization days >30 days in the past year).
Pregnancy or lactation.
The study population consists of patients with locally advanced esophageal squamous cell carcinoma (ESCC) diagnosed at Henan Cancer Hospital between January 2013 and December 2025. Eligible patients are those who meet the inclusion criteria and initiated either neoadjuvant chemoradiotherapy (nCRT) or neoadjuvant immunochemotherapy (nICT) within 180 days after Time Zero. Patients are identified from electronic health records (EHR) including medical records, pathology reports, imaging reports, and prescription systems.
Cohort
Retrospective
Radiotherapy
RadiationConcurrent radiotherapy administered as part of neoadjuvant chemoradiotherapy, typically 41.4-50.4 Gy in fractionated doses, combined with platinum-based chemotherapy.
Platinum-based Chemotherapy
DrugPlatinum-based chemotherapy administered as part of neoadjuvant treatment, combined with either concurrent radiotherapy (nCRT) or PD-1 inhibitors (nICT).
PD-1 Inhibitor
DrugPD-1 inhibitors administered as part of neoadjuvant immunochemotherapy, combined with platinum-based chemotherapy for 2-4 cycles.
Overall Survival (OS)
Overall Survival (OS) is defined as the time from Time Zero (the day before the first neoadjuvant treatment order) to death from any cause. Patients alive at the time of analysis are censored at the date of last known contact.
Event-Free Survival (EFS)
Event-Free Survival (EFS) is defined as the time from Time Zero to the first occurrence of death, disease progression, local recurrence, distant metastasis, or inoperability, whichever occurs first.
Pathological Complete Response (pCR) Rate
Pathological complete response (pCR) is defined as the absence of viable tumor cells in the primary tumor and all resected lymph nodes (ypT0 ypN0) on postoperative pathological examination.
Tumor Regression Grade (TRG)
Tumor regression grade assessed according to Mandard criteria or Chinese standard (TRG 0-3) on postoperative pathological examination.
R0 Resection Rate
R0 resection rate is defined as the proportion of patients achieving microscopically margin-negative resection on postoperative pathological examination.
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