Genomic Profiles as Predictors of Occult Lymph Node Metastasis and Clinical Outcomes in Early-Stage Clinical N0 Non-Small Cell Lung Cancer

Abstract

ObjectiveOccult lymph node (LN) metastasis, indicating pathological LN involvement, is often observed in clinical N0 (cN0) early-stage non-small cell lung cancer (NSCLC). Identifying preoperative predictors of occult LN metastasis (pathologically N1 and N2) is crucial for determining the surgical procedure for cN0 NSCLC. This study aimed to investigate the role of genetic mutations in predicting occult LN metastasis and their influence on surgical strategies.Materials and MethodsWe retrospectively reviewed patients who underwent lobectomy or segmentectomy for cN0 NSCLC with pathological stages higher than IB, between May 2017 and April 2024. Clinicopathological characteristics and genetic mutations were analyzed. Occult LN metastasis was not detected by imaging but identified through histopathology.ResultsWe evaluated 644 patients, median age 71 years. Occult LN metastases were observed in 179 (27.8%) patients. EGFR mutations and ALK rearrangements were significantly associated with occult LN metastasis (EGFR, p=0.04; ALK, p=0.007), particularly EGFR exon 19 deletions (p=0.006). Multivariate analysis confirmed these as significant predictors (p=0.006). Notably, patients with these mutations had longer recurrence-free survival (RFS) than those without (HR 1.27, 95% CI 0.90–1.80, p=0.02). RFS was significantly shorter after segmentectomy (HR 3.18, 95% CI 1.02–9.99, p=0.04) and longer after lobectomy (HR 1.28, 95% CI 0.87–1.90, p=0.01).ConclusionGenomic profiles, such as EGFR mutations and ALK rearrangements, are associated with occult LN metastasis and outcomes in cN0 NSCLC. Integrating genetic assessments into preoperative planning may optimize surgical strategies and improve prognosis.

Note:
Funding declaration: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Conflict of Interests: The authors declare no conflicts of interest related to this manuscript.

Ethical Approval: The proposed study was approved by the Ethics Committee of the National Cancer Center Hospital (2015-355).

Keywords: occult lymph node, non-small cell lung cancer, genomic profile, EGFR mutations, ALK rearrangements