# Analyses on patterns of lymph node metastasis and its impact on prognosis in thoracic esophageal squamous cell carcinoma treated with neoadjuvant immunochemotherapy versus chemotherapy alone: a single-center, retrospective cohort study

## TL;DR

Adding immunotherapy to chemotherapy before surgery for esophageal cancer reduces lymph node metastasis and postoperative recurrence.

## Contribution

Demonstrates that neoadjuvant immunochemotherapy reduces lymph node metastasis and recurrence in thoracic esophageal squamous cell carcinoma.

## Key findings

- Neoadjuvant immunochemotherapy (nICT) achieved a higher pathological complete response rate compared to chemotherapy alone.
- nICT was associated with a lower metastatic lymph node ratio and reduced lymph node involvement in key stations.
- nICT significantly reduced postoperative recurrence rates and improved event-free survival.

## Abstract

To compare the patterns of lymph node metastasis (LNM) in patients with thoracic esophageal squamous cell carcinoma (TESCC) treated with neoadjuvant immunochemotherapy (nICT) versus neoadjuvant chemotherapy (nCT) alone and its impact on prognosis and potential clinical implications.

A single-center retrospective cohort study was conducted on 441 patients with locally advanced TESCC who underwent nCT (n=179) or nICT (n=262) followed by esophagectomy. LNM patterns were analyzed according to the Japanese Classification of Esophageal Cancer (12th Edition), using metrics including lymph node ratio (LNR), lymph node metastasis rate and actual lymph node metastasis rate for specific stations. Postoperative recurrence patterns, overall survival (OS), and event-free survival (EFS) were also evaluated.

Compared with nCT, nICT achieved a significantly higher pathological complete response (pCR) rate (22.1% vs. 6.7%, p < 0.001) and a lower metastatic lymph node ratio (LNR) (3.5% vs 6.2%, p < 0.001). Although the overall LNM rate was similar between groups, nICT demonstrated reduced lymph node involvement in several key station lymph nodes, particularly level 7 (along the left gastric artery), with lower the lymph node metastasis rate (LNMR2) (7.6% vs. 14.5%, p = 0.020) and the actual metastasis rate (LNMR3) (8.4% vs. 16.8%, p = 0.012). The overall recurrence/metastasis rate was significantly lower in the nICT group (36.2% vs. 56.8%, p < 0.001), with a notable reduction of recurrence at the anastomotic site. In multivariable analyses, nICT independently predicted lower recurrence risk (adjusted OR = 0.55, p = 0.013) and improved EFS (HR = 0.65, p = 0.001) while OS was not statistically different between groups.

In comparison to nCT alone, nICT was significantly associated with deeper pathological response, lower LNM burden, and reduced postoperative recurrence in TESCC.