Preoperative circulating tumor DNA detection and occult lymph node metastases in clinical stage I lung cancer: The lung DETECT study

Objective: To investigate whether preoperative circulating tumor (ct)DNA detection is associated with pathologic upstaging, including occult lymph node (LN) metastases, in clinical stage I non-small cell lung cancer (NSCLC). We hypothesized that preoperative ctDNA detection may identify patients at increased risk of higher-stage disease, including occult nodal involvement, who may benefit from more comprehensive staging. Methods: CtDNA Lung DETECT (NCT05254782) is a multicenter prospective cohort study in patients with clinical stage I NSCLC and preoperative ctDNA detection, using a tumor-informed ctDNA assay collected preoperatively. All patients underwent guideline-concordant staging with positron emission tomography/computed tomography (CT), CT-guided biopsy, and/or endobronchial ultrasound (EBUS). Results: = .003). Conclusions: Preoperative ctDNA detection was associated with a higher likelihood of pathologic upstaging, including occult LN metastasis in patients with clinical stage I NSCLC. These findings support further evaluation of ctDNA as a complementary tool to refine risk stratification and guide decisions regarding invasive mediastinal staging or perioperative treatment in clinical stage 1 NSCLC.