Sentinel Lymph Node in Non-Small Cell Lung Cancer: Longterm Outcomes and Immunopathological Consequences

Author(s): Florent Stasiak, Loic Reppel, Mickael Schaeffer, Guillaume Gauchotte, Arthur Streit, Joelle Siat, Lucie Schnedecker, Joseph Seitlinger, Stephane Renaud.

Background: Lymph-node staging is pivotal in non-small-cell lung cancer (NSCLC). While systematic lymph-node dissection (SLND) is standard, it may blunt anti-tumour immunity. Sentinel lymph-node (SLN) mapping could deliver robust staging with less immune disruption. We assessed survival outcomes and lymph-node immune profiles associated with SLN mapping in NSCLC surgery.

Methods: This retrospective study of 266 patients who underwent major lung resection with SLN identification (Dec 2020–Sep 2025) assessed overall survival (OS) and disease-free survival (DFS). Translational analyses compared immune populations in SLN vs. non-SLN and node-positive (pN+) vs. node-negative (pN0) samples, using immunohistochemistry (IHC; 10 SLN and 10 pN+ patients) and flow cytometry (FCM; 13 pN0 SLN and 4 pN+ patients).

Results: SLN was detected in 80.1% of patients (213/266). In patients with NSCLC, upstaging occurred in 6.6% (11/167), with a false-negative rate of 2.6% (4/156). Median OS was 27 months for SLN pN+ and not reached for SLN pN0 (HR 9.7, 95% CI 2.61–36.22; p<0.001); median DFS was 12 months for SLN pN+ and not reached for SLN pN0 (HR 10.1, 95% CI 3.68–27.83; p<0.001). IHC and FCM demonstrated a comparable immune environment between SLNs and non-SLNs in pN0 patients for key immune compartments (CD4, CD8 T cells, memory subsets), while metastatic lymph nodes displayed disrupted architecture and altered cytotoxic Tcell markers.

Conclusions: SLN micrometastasis is a strong prognostic marker. SLN mapping may provide accurate staging while preserving nodal immunity, representing a conservative alternative to SLND in early-stage NSCLC, and warrants confirmation in larger, prospective studies.