Endobronchial Ultrasound Staging of Operable NSCLC: Do Triple Normal Lymph Nodes Require Routine Biopsy?

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Staging guidelines for lung cancer recommend endobronchial ultrasound (EBUS) and systematic biopsy of at least 3 mediastinal lymph node (LN) stations for accurate staging. A 4-point ultrasonographic score (Canada Lymph Node Score- CLNS) was developed to determine the probability of malignancy in each LN. A LN with a CLNS<2 is considered low probability for malignancy. We hypothesized that, in patients with cN0 non-small cell lung cancer, LNs with CLNS<2 may not require routine biopsy because they represent true node negative disease.Do lymph nodes considered triple normal on CT, PET, and CLNS require routine biopsy?LNs were evaluated for ultrasonographic features at the time of EBUS and the CLNS was applied. “Triple Normal” LNs were defined as cN0 on computed tomography (short axis <1cm), positron emission tomography (no hypermetabolic activity), and EBUS (CLNS<2). Specificity and negative predictive value (NPV) were calculated against the gold-standard pathological diagnosis from surgically excised specimens.In total, 143 LNs from 57 cN0 patients were assessed. Triple Normal LNs had a specificity and NPV of 60% (95%CI:51.2-68.3%) and 93.1% (95%CI:85.6-97.4%), respectively. After pathological assessment, only 5.6% (n=8/143) of Triple Normal nodes were proven to be malignant.At the time of staging for lung cancer, combining CT, PET and CLNS criteria can identify Triple Normal LNs which have a high NPV for malignancy. This raises the question of whether Triple Normal LNs require routine sampling during EBUS-TBNA. A prospective trial is required to confirm these findings.

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