Longitudinal Undetectable Molecular Residual Disease Defines Potentially Cured Population in Localized Non-Small Cell Lung Cancer

The effi cacy and potential limitations of molecular residual disease (MRD) detec-tion urgently need to be fully elucidated in a larger population of non-small cell lung cancer (NSCLC). We enrolled 261 patients with stages I to III NSCLC who underwent defi nitive surgery, and 913 peripheral blood samples were successfully detected by MRD assay. Within the popu-lation, only six patients (3.2%) with longitudinal undetectable MRD recurred, resulting in a negative predictive value of 96.8%. Longitudinal undetectable MRD may defi ne the patients who were cured. The peak risk of developing detectable MRD was approximately 18 months after landmark detec-tion. Correspondingly, the positive predictive value of longitudinal detectable MRD was 89.1%, with a median lead time of 3.4 months. However, brain-only recurrence was less commonly detected by MRD ( n = 1/5, 20%). Further subgroup analyses revealed that patients with undetectable MRD might not benefi t from adjuvant therapy. Together, these results expound the value of MRD in NSCLC. SIGNIFICANCE: This study confi rms the prognostic value of MRD detection in patients with NSCLC after defi nitive surgery, especially in those with longitudinal undetectable MRD, which might represent the potentially cured population regardless of stage and adjuvant therapy. Moreover, the risk of devel-oping detectable MRD decreased stepwise after 18 months since landmark detection.