Invasive Staging Procedures Do Not Prevent Nodal Metastases from Being Missed In Stage I Lung Cancer.

BACKGROUND: Up to 20% of clinical stage I lung cancer patients harbor lymph node metastases that go undetected (missed) during the clinical staging evaluation. We investigated to what degree the addition of invasive nodal staging procedures to imaging, as currently practiced, prevents radiographically-occult nodal metastases from being missed during the clinical staging evaluation. METHODS: Treatment-naive patients, imaged by PET and CT scanning, that underwent lobectomy for clinical stage I lung cancer from 2012-17 in the Society of Thoracic Surgeons General Thoracic Surgery Database were studied. Rates of missed nodal metastases (MNM) (i.e. nodal metastases in lobectomy specimens - undetected during clinical staging evaluation) were determined. Risk factors were assessed with multivariable modeling. RESULTS: Of the 30,685 clinical stage I patients identified, 3,895 (12.7%) underwent preoperative EBUS and 3,341 (10.9%) underwent mediastinoscopy. Invasive staging was more common with tumors >2cm (66.4% vs 50.2%, p<0.001), and squamous histology (26.9% vs. 16.9% p<0.001). MNM were discovered in 14.7% of patients, including 20.1% (95%CI:18.8-21.5%) of patients that had undergone EBUS and 18.2% (95%CI:16.7-19.6%) of mediastinoscopy patients. Hilar nodes were most often "missed" (9.5%). Using cut-points in tumor size, histology, laterality and age, patients could be stratified into particularly high (25% MNM) and low (6% MNM) risk cohorts. CONCLUSIONS: Substantial risk of occult lymph node metastases persists in patients with clinical stage I lung cancer despite negative invasive nodal staging, PET and CT scans. In the absence of a thorough surgical nodal evaluation, early-stage lung cancer patients are at risk of undertreatment.