This retrospective real-world study aimed to compare neoadjuvant immunochemotherapy (NICT) and neoadjuvant chemoradiotherapy (NCRT) followed by esophagectomy in patients with locally advanced esophageal squamous cell carcinoma (ESCC). A total of 203 consecutive patients treated at Sichuan Cancer Hospital between March 2018 and March 2022 were analyzed (NICT: 59; NCRT: 144). The primary endpoints were overall survival (OS) and disease-free survival (DFS); secondary endpoints included pathological complete response (pCR), tumor regression grade (TRG), and R0 resection rate. After inverse probability of treatment weighting adjustment, baseline characteristics were balanced between groups. Both groups achieved comparable long-term OS and DFS, while NCRT showed higher rates of local pathological response. Exploratory subgroup analysis suggested that patients achieving pCR after NICT might have superior survival outcomes. The study indicates that NICT provides similar long-term survival compared to NCRT and may offer immunologic advantages for selected responders, warranting further validation in prospective multicenter trials.

Inclusion Criteria:

• Age 18-80 years
• Histologically confirmed thoracic ESCC
• Clinical stage cT1N+M0 or cT2-4aN0-3M0
• Received neoadjuvant therapy (immunochemotherapy or chemoradiotherapy) followed by esophagectomy

Exclusion Criteria:

• History of other malignancies
• Did not complete neoadjuvant therapy or required salvage surgery
• Incomplete baseline or follow-up data

Individual participant data (IPD) will not be shared because this is a retrospective study based on patient medical records, and the data contain potentially identifiable clinical information. Ethical approval for this study was granted under the condition that data would be used only for internal analysis at Sichuan Cancer Hospital & Institute. De-identified summary-level results are provided within the publication.