Preoperative circulating tumor DNA detection and occult lymph node metastases in clinical stage I lung cancer: The
Zachary Coyne1, Jamie Feng1, Sameena Khan1
1Division of Medical Oncology, Princess Margaret Cancer Centre/University Health Network, Toronto, Ontario, Canada.
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:
Between July 2021 and September 2024, 14 of 153 patients with preoperative clinical stage I NSCLC had occult LN metastases discovered. Of these 14 LN-positive patients, 7 had prior EBUS with LN sampling, all with negative cytologic results. The other 7 were diagnosed via CT-guided biopsy alone according to standard guidelines. Preoperative ctDNA in plasma was detected in 8 of the 14 LN-positive patients. In the larger cohort, 34 of 153 patients had ctDNA detected preoperatively, 24% of whom had occult LN metastases at time of resection. In contrast, only 5% of patients without detectable ctDNA prior to surgery had occult nodal involvement (P = .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.
