Prognostic Implications of Lymph Node Status in Non-Small-Cell Lung Cancer Patients Before and After Neoadjuvant Chemoimmunotherapy: A Multicenter Retrospective Study.

Background: In patients with non-small-cell lung cancer (NSCLC) treated with neoadjuvant chemoimmunotherapy, lymph node (LN) status is classified as ypN0 and ypN+. However, ypN0 includes patients who either had LN metastasis before neoadjuvant therapy (cN+/ypN0) or those who never developed LN metastasis (cN0/ypN0). The prognostic implications of these different LN statuses are not well understood.

Methods: A retrospective analysis was conducted on patients with NSCLC who underwent surgery after neoadjuvant chemoimmunotherapy at 4 centers in China from 2019 to 2022. Patients were grouped by their LN status into ``natural'' N0 (cN0/ypN0), ``downstaged'' N0 (cN+/ypN0), and ypN+ (cN+/ypN+).

Results: Out of 527 initially enrolled patients, 186 met the inclusion criteria: 34 (18.3%) had ``natural'' N0, 95 (51.1%) had ``downstaged'' N0, and 57 (30.6%) had ypN+. The median follow-up was 24 months (11-64 months). Disease-free survival (DFS) and overall survival (OS) were significantly lower in ypN+ compared to ``natural'' N0 and ``downstaged'' N0 (DFS: P < .001; OS: P < .001). However, no significant difference in either DFS (P = .695) or OS (P = .814) were observed between ``natural'' N0 and ``downstaged'' N0. Subgroup analysis showed that the MPR/ypN0 group had significantly better DFS compared to the non-MPR/ypN0 (P = .008), MPR/ypN+ (P = .028), and non-MPR/ypN+ groups (P < .001). For OS, MPR/ypN0 group was significantly superior to non-MPR/ypN+ (P < .001) and showed a trend toward better OS than non-MPR/ypN0 (P = .067) and MPR/ypN+ (P = .067). Notably, no significant differences were observed in either DFS (P = .908) or OS (P = .943) between non-MPR/ypN0 and MPR/ypN+ groups. The non-MPR/ypN+ group had the poorest survival outcomes in both DFS and OS.

Conclusions: Achieving ypN0 status after neoadjuvant chemoimmunotherapy strongly predicts favorable outcomes in patients with NSCLC, regardless of pretreatment cN status. Combining MPR with LN status effectively differentiates patient prognoses.