Prevalence and Risk Factors for Pathologic N2 Disease in Resected Lung Cancers Assessed as N0 or N1 Disease on Preoperative Imaging

BACKGROUND. For certain patients with lung cancer, guidelines recommend endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) as the primary method to evaluate for metastatic mediastinal lymph nodes defining pN2 disease. EBUS-TBNA has associated costs and complications and possibly limited availability. OBJECTIVE. The purpose of the present study was to investigate the prevalence of and risk factors for pN2 disease in patients undergoing resection of lung cancer who were assessed as having radiologic N0 or N1 disease. METHODS. This retrospective study included 3581 patients (mean age, 63.8 ± 9.4 [SD] years; 1917 men and 1664 women) with lung cancer who underwent chest CT and FDG PET/CT showing radiologic N0 or N1 disease before resection between January 2015 and December 2021. Tumor characteristics were assessed on chest CT. Patients were assessed for the presence of guideline-based indications for EBUS-TBNA as evaluation for imaging-occult N2 disease. Pathologic N categories were determined from surgical specimens. Preoperative risk factors for pN2 disease were identified using logistic regression analyses. RESULTS. A total of 1936 patients had radiologic N0 disease without an EBUS-TBNA indication, 1348 had radiologic N0 disease with an EBUS-TBNA indication, and 297 had radiologic N1 disease. These groups had a prevalence of pN2a disease of 4.1%, 6.5%, and 18.5%, respectively, and a prevalence of pN2b disease of 1.2%, 2.4%, and 14.8%, respectively. In multivariable analyses, independent risk factors for pN2 disease were, in patients with radiologic N0 disease without an EBUS-TBNA indication, female sex (OR = 1.66 [95% CI, 1.08-2.54]), larger size of solid portion of the tumor (OR = 1.05 [95% CI, 1.01-1.10]), pure-solid nodule (OR = 5.53 [95% CI, 3.15-9.72]), and spiculation (OR = 2.66 [95% CI, 1.72-4.11]); in patients with radiologic N0 disease with an EBUS-TBNA indication, they were younger age (OR = 0.97 [95% CI, 0.96-0.99] per year), pure-solid nodule (OR = 1.75 [95% CI, 1.10-2.80]), and lobulation (OR = 1.96 [95% CI, 1.23-3.11]); and in patients with radiologic N1 disease, they were younger age (OR = 0.973 [95% CI, 0.948-0.999] per year), female sex (OR = 2.91 [95% CI, 1.66-5.11]), and spiculation (OR = 2.81 [95% CI, 1.66-4.76]). CONCLUSION. pN2b disease was uncommon in patients with radiologic N0 disease, regardless of indications for EBUS-TBNA, and its prevalence increased in patients with radiologic N1 disease. CLINICAL IMPACT. The identified risk factors can inform patient selection for EBUS-TBNA, to aid in the detection of occult pN2 disease.