Identifying factors causing failure of nodal staging by endobronchial ultrasound-guided transbronchial needle aspiration in non-small cell lung cancer

Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is recommended for nodal staging in non-small cell lung cancer (NSCLC). Although this method may rarely fail, reports on the causes are few. We therefore retrospectively investigated the factors causing failure of nodal staging by EBUS-TBNA.

Methods: Consecutive patients who underwent EBUS-TBNA at National Cancer Center Hospital between January 2017 and December 2020 for systematic nodal staging in NSCLC were extracted. The nodal stages at diagnosis including EBUS-TBNA and at treatment were investigated separately, and unmatched cases were defined as failures. Factors associated with them were explored while dividing the cases into punctured and not-punctured groups.

Results: Of the 264 patients, 21 (8.0%) failed the nodal staging: 10 (3.8%) in the punctured group and 11 (4.2%) in the not-punctured group. The latter was subdivided into the following three categories: (I) difficult-to-reach; (II) omission due to false-positive rapid on-site cytologic evaluation (ROSE) results; and (III) non-significant EBUS findings. The nodal staging failure rate was significantly higher in cases with driver oncogenes positive than in those negative (16.1% vs. 3.3%, P=0.026) for adenocarcinomas. Note that all cases categorized as non-significant EBUS findings involved various driver oncogenes.

Conclusions: The present study demonstrated the risk of false positives with ROSE and the involvement of driver oncogenes as factors associated with nodal staging failure in NSCLC by EBUS-TBNA, in addition to limitations of the procedure itself, including sampling performance and reachability. Especially in adenocarcinoma patients with driver oncogenes, their nodal staging results should be interpreted cautiously.