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 previous published cohort study of 261 NSCLC patients undergoing complete resection. 261 patients with stage I-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 31st, 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 times of 5.2 months. Negative predictive values were 76.5% and 93.2%, respectively. Patients with landmark undetectable MRD could not be benefited 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 six 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 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. And postoperative longitudinal undetectable MRD can indicate a cured population.
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