Follow-up Analysis Enhances Understanding of Molecular Residual Disease in Localized Non-Small Cell Lung Cancer.

Abstract

The prognostic value of molecular residual disease (MRD) in non-small cell lung cancer (NSCLC) is well established, with treatment-guiding results anticipated. Here, we present updated analyses from our previously published cohort study of 261 patients with NSCLC undergoing complete resection. A total of 261 patients with stage I to III lung cancer who underwent radical surgery were enrolled. Enrolled patients underwent follow-up blood draws according to the predefined time points after surgery. As of December 31, 2023, with a median follow-up of 43.4 months, 948 postoperative blood samples were collected. Landmark and longitudinal MRD exhibited positive predictive values of 91.3% and 92.8%, respectively, with a median lead time of 5.2 months. Negative predictive values were 76.5% and 93.2%, respectively. Patients with landmark undetectable MRD could not benefit from adjuvant therapy through the updated follow-up (P = 0.529). Among the 13 patients with recurrent NSCLC and longitudinal undetectable MRD, seven (53.8%) had brain-only metastases, and four (30.8%) had no updated blood samples for over 6 months prior to recurrence. Besides, for those with longitudinal detectable MRD, higher maximum variant allele frequency (>0.55%) and ctDNA level (>13 hGE/mL) were associated with a high risk of short-term recurrence. Additionally, updated follow-up data further support that the peak time for detectable MRD was 18 months after landmark detection. These findings suggest the significant potential of MRD in guiding personalized treatment for NSCLC. Postoperative longitudinal undetectable MRD can indicate a cured population.