Identifying Patients With High-Risk Stage I NSCLC Using a Tumor-Informed Plasma ctDNA Assay

INTRODUCTION: Circulating tumor DNA (ctDNA) has emerged as an important prognostic factor in patients with cancer. Management of early stage NSCLC remains challenging with a high rate of disease recurrence. METHODS: In this prospective cohort, 153 patients with clinical stage I NSCLC (75.8% pathologic stage I) underwent real-time plasma ctDNA testing using a tumor-informed whole exome sequencing approach, RaDaR. RESULTS: Preoperative ctDNA was detected in 22.4% of patients (6 wk of median turnaround time) and was significantly associated with recurrence-free survival (RFS) (hazard ratio: 3.81, p = 0.006). No patients with pathologic stage I disease had detectable postoperative ctDNA. The 2-year RFS was 84.2%, with inferior outcomes among patients with preoperative ctDNA detected (69.1%). In pathologic stage I NSCLC, preoperative ctDNA detection and invasive tumor size remained independently associated with RFS. CONCLUSION: Here, we demonstrate the clinical feasibility of plasma ctDNA to inform treatment decision-making in stage I NSCLC. CLINICALTRIALS: gov identifier: NCT05254782.