Liquid Biopsy-Guided Surgical Decision-Making in Oligometastatic Non-Small Cell Lung Cancer: Toward Dynamic Risk Stratification in the Multidisciplinary Era

Oligometastatic non-small cell lung cancer (NSCLC) is defined anatomically by a threshold of five or fewer metastatic lesions across three or fewer organs. That definition is a proxy for a biological question it cannot answer: whether the metastatic process has been arrested at a stage where eradication of all detectable disease is curative. Randomized phase II trials of local consolidative therapy have shown median progression-free survival gains of 6.2 and 8.0 months and, in one trial, a median overall survival of 41.2 months vs. 17.0 months, yet median progression-free survival with local therapy did not exceed 14.2 months, and the phase II/III NRG-LU002 trial found no significant survival benefit from adding local therapy to maintenance therapy. Circulating tumor DNA (ctDNA) measures molecular disease burden. In resectable NSCLC, preoperative ctDNA detection is associated with a higher risk of relapse; in oligometastatic disease, the baseline sample is instead the quantitative reference for response. ctDNA kinetics during induction therapy track systemic response before any operation, although no response threshold has been validated, and postoperative molecular residual disease anticipates radiological relapse by a median of approximately 5 months. This review synthesizes the evidence linking liquid biopsy to surgical decision-making and proposes, as a hypothesis for prospective testing, a dynamic risk stratification framework anchored on five plasma sampling points. We separate established prognostic evidence from untested hypotheses, address oncogene-driven and other oligometastatic states, and define the assay requirements, confounders and trial designs needed before ctDNA can select patients for or against thoracic resection.