Distribution and rate of lymph node metastasis following neoadjuvant chemoimmunotherapy in non-small cell lung cancer

Neoadjuvant chemoimmunotherapy (NCIT) has emerged as a standard care for resectable non-small cell lung cancer (NSCLC). However, the pattern of lymph node metastasis (LNM) following this treatment remains poorly characterized. This study aimed to elucidate the distribution and rate of LNM after NCIT.

We retrospectively analyzed 394 NSCLC patients who received NCIT followed by R0 resection at Shanghai Pulmonary Hospital between 2019 and 2022. Pathological data were evaluated to determine LNM distribution and rate, with subgroup analyses performed based on tumor location and histology. Multivariable logistic regression identified independent predictors of nodal downstaging. Kaplan-Meier analyses evaluated survival outcomes based on the extent of lymphadenectomy. Multivariable Cox proportional hazards regression models were performed to identify independent prognostic factors associated with disease-free survival (DFS) and overall survival (OS).

Among the 394 patients, predominant LNM stations were 13R (9.4%), 7 (9.4%), 13L (5.8%), 2R (5.6%), 4R (5.3%), and 10R (5.1%). N1 metastasis rates were generally higher across all lobes, especially at station 13. Notably, right lower lobe tumors exhibited high metastasis rates to the superior mediastinum. Survival analysis demonstrated a trend toward more favorable DFS among patients receiving systematic lymph node dissection (SLND) compared with those undergoing non-SLND (P = 0.182). Similarly, patients with ≥ 6 dissected lymph node stations showed a trend toward more favorable DFS compared with those with < 6 dissected lymph node stations (P = 0.100); however, neither association reached statistical significance. Furthermore, multivariable Cox regression identified non-adenocarcinoma histological types (squamous cell carcinoma: HR = 0.58, 95% CI: 0.37-0.92, P = 0.020; others: HR = 0.34, 95% CI: 0.17-0.70, P = 0.004) as independent predictors of improved DFS. For OS, advanced baseline clinical N stage (cN1 vs. cN0: HR = 8.48, 95% CI: 1.07-66.98, P = 0.043) was confirmed as an independent risk factor for worse survival, whereas non-adenocarcinoma/non-squamous histology (HR = 0.13, 95% CI: 0.02-0.95, P = 0.044) served as an independent protective factor.

Post-NCIT lymph node involvement patterns in NSCLC patients varied according to primary tumor location. SLND and the retrieval of ≥ 6 dissected lymph node stations were associated with favorable DFS trends, although these findings were not statistically significant and require further validation.