Endobronchial Ultrasound Staging of Operable Non-small Cell Lung Cancer Do Triple-Normal Lymph Nodes Require Routine Biopsy?

BACKGROUND: Staging guidelines for lung cancer recommend endobronchial ultrasound (EBUS) and systematic biopsy of at least three mediastinal lymph node (LN) stations for accurate staging. A four-point ultrasonographic score (Canada Lymph Node Score [CLNS]) was developed to determine the probability of malignancy in each LN. A LN with a CLNS of < 2 is considered low probability for malignancy. We hypothesized that, in patients with cN0 non-small cell lung cancer, LNs with CLNS of < 2 may not require routine biopsy because they represent true node-negative disease. RESEARCH QUESTION: Do LNs considered triple normal on CT scanning, PET scanning, and CLNS evaluation require routine biopsy? STUDY DESIGN AND METHODS: LNs were evaluated for ultrasonographic features at the time of EBUS and the CLNS was applied. Triple-normal LNs were defined as cN0 on CT scanning (short axis, < 1 cm), PET scanning (no hypermetabolic activity), and EBUS (CLNS, < 2). Specificity and negative predictive value (NPV) were calculated against the gold standard pathologic diagnosis from surgically excised specimens. RESULTS: In total, 143 LNs from 57 cN0 patients were assessed. Triple-normal LNs showed a specificity and NPV of 60% (95% CI, 51.2%-68.3%) and 93.1% (95% CI, 85.6%-97.4%), respectively. After pathologic assessment, only 5.6% (n = 8/143) of triple-normal nodes were proven to be malignant. INTERPRETATION: At the time of staging for lung cancer, combining CT scanning, PET scanning, and CLNS criteria can identify triple-normal LNs that have a high NPV for malignancy. This raises the question of whether triple-normal LNs require routine sampling during EBUS and transbronchial needle aspiration. A prospective trial is required to confirm these findings.