Prognostic stratification of early-stage NSCLC patients using preoperative circulating tumor DNA (ctDNA).

8031 Background: Curative-intent surgery for early-stage non-small-cell lung cancer (NSCLC) is followed by relapse in approximately 20–30% of patients. We previously reported interim results of the prospective MUSETALK-Lung01 study (multiomics sequencing technique application kick-start), showing that pre-operative, ctDNA positivity predicted increased relapse risk. Here we present the final analysis of the full cohort and incorporate pathological risk factors to conduct a more comprehensive prognostic evaluation for early-stage NSCLC. Methods: The MUSETALK-Lung01 study is a prospective, longitudinal, observational study designed to evaluate the clinical utility of a tumor-naïve ctDNA assay in patients with early-stage NSCLC. Cell-free DNA (cfDNA) was extracted, and subjected to CanCatch Surf test as described previously. The assay algorithm reports both the ctDNA detection status (positive/negative) and the estimated ctDNA levels. Longitudinal data, including vital status, treatment, relapse, and survival status, were collected over 5 years. The study was approved by the institutional review board or ethics committee at each site, with all participants providing written informed consent. Results: The complete cohort of MUSETALK-Lung01 consisted of 455 early-stage NSCLC patients, among whom the median follow-up time was 63 months, with a 2-year recurrence rate of 7.0% and a presurgical ctDNA positivity rate of 6.4%. To identify clinical and biological factors associated with survival, both univariate and multivariate analyses were performed. Presurgical ctDNA positivity was strongly associated with inferior recurrence outcomes (χ 2 p < 1 x 10 -9 ), indicating that tumor burden can be prognostic beyond clinical stage and pathological conditions. Specifically, among clinical stage I lung adenocarcinoma (LUAD) patients, ctDNA detection demonstrated robust prognostic stratification for recurrence risk (2-year RFS: 60% [95% CI: 40%–91%] vs. 96% [95% CI: 94%–98%]; log-rank p < 1 x 10 -7 ). Similar prognostic value of ctDNA was observed in stage II-IIIA LUAD patients, albeit with reduced discriminative power (log-rank p < 0.01). After incorporating pathological information, the performance of prognostic stratification was further improved. Conclusions: By evaluating ctDNA abundance, we provide highly sensitive and specific prognostic assessments and risk stratification for early-stage NSCLC patients. The non-invasive, nature of this test enables precision peri-operative management and selection of patients who may benefit from innovative treatments, with the potential to improve survival.