Postoperative Radiotherapy and Lymph Node Dissection After Neoadjuvant Immunochemotherapy for Esophageal Squamous Cell Carcinoma

Impact of Postoperative Radiotherapy and Lymph Node Dissection on Recurrence and Distant Metastasis After Neoadjuvant Immunochemotherapy and R0 Resection for Esophageal Squamous Cell Carcinoma: A Multicenter Retrospective Real-World Study

This is a multicenter, retrospective observational study using existing medical records of patients with esophageal squamous cell carcinoma who received at least two cycles of neoadjuvant immunochemotherapy followed by curative surgery with complete tumor removal and negative surgical margins between January 2021 and December 2024.

The main aim of this study is to evaluate whether postoperative radiotherapy is associated with better control of cancer recurrence in the surgical area and regional lymph nodes, and whether this association differs according to the extent and number of lymph nodes removed during surgery. Patients will not be assigned to any treatment as part of this study. Outcomes will be compared according to postoperative radiotherapy status and lymph node dissection characteristics.

The primary outcome is locoregional recurrence-free survival. Secondary outcomes include disease-free survival, overall survival, and distant metastasis-free survival. Clinical, surgical, pathological, treatment, and follow-up information will be collected from electronic medical records at six esophageal cancer centers. Approximately 300 patients are expected to be included.

Inclusion Criteria:

• Histologically confirmed esophageal squamous cell carcinoma.
• Received at least two cycles of neoadjuvant immunochemotherapy consisting of a PD-1 or PD-L1 inhibitor combined with platinum- and taxane-based chemotherapy.
• Underwent planned curative esophagectomy with R0 resection, defined as microscopically negative surgical margins.
• Operative records and postoperative pathology reports documented the number of lymph nodes removed.
• Complete information on postoperative management was available, including postoperative radiotherapy, systemic therapy, or observation. For patients who received postoperative radiotherapy, information on the radiation field and dose was available.
• At least 12 months of postoperative follow-up information was available.

Exclusion Criteria:

• Histological type other than esophageal squamous cell carcinoma, including adenocarcinoma or neuroendocrine carcinoma.
• Received neoadjuvant chemoradiotherapy, neoadjuvant immunochemoradiotherapy, neoadjuvant chemotherapy alone, or no neoadjuvant treatment.
• Distant metastatic disease at the initial diagnosis.
• Underwent R1 or R2 resection.
• Death within 90 days after surgery.
• History of another malignancy within 5 years before study entry, except for cured nonmelanoma skin cancer or carcinoma in situ, or a history of thoracic radiotherapy.
• Missing key information required to determine the extent of lymph node dissection, postoperative radiotherapy details, date of recurrence, or date of death.