Occult lymph node metastases in clinical N0/N1 NSCLC; A single center in-depth analysis

Objectives: Lymph node staging in patients with non-small cell lung cancer is crucial for determining prognosis and treatment. Our objective was to evaluate the clinicalto pathological agreement of guideline-concordant nodal staging in patients with resectable NSCLC and assess occurrence and distribution of occult lymph node metastases (OLM). Materials and methods: In a retrospective single center cohort study (n = 390), we analyzed all surgically treated NSCLC patients from January 2015 until April 2019. Patients were classified into sub-groups (1) mediastinal staging by PET-CT/CT-scan (IMAGE-group) or (2) invasive staging by endobronchial ultrasound and mediastinoscopy (INVAS-group). Agreement between final clinical (cN) and pathological nodal stage (pN) and the presence and location of OLM are analyzed. Results: Agreement between cN- and pN-stage was 86.3 % in the IMAGE-group (n = 117) and 50.9 % in the INVAS-group (n = 167). Occult N1 disease was found in 33 patients (16.6 % in cN0) of which 52 % occurred in LN-regions 12-14. Occult N2 disease was found in 20 cases (6.5 % in cN0 and 12.7 % in cN1). Combined, 23.1 % of all pre-operatively cN0-staged patients (n = 46/199) had OLM (pN+), of which 12.1 % (24/199) had metastases in regions 5-6 and/or 12-14. Of all patients with OLM, 50.0 % (23/46) had primary tumors <= 30 mm. Conclusion: OLM are frequently identified in clinically N0/N1 NSCLC, also in tumors <3 cm, and often in regions beyond reach of current staging techniques. These findings should be addressed when non-surgical treatment or sub-lobar resections are considered for early stage lung cancer.