Liquid Biopsy-Guided Surgical Decision-Making in Oligometastatic Non-Small Cell Lung Cancer: Toward Dynamic Risk Stratification in the Multidisciplinary Era
5 affiliations
- 1Department of Cardiac Surgery Research, Lankenau Institute for Medical Research, Main Line Health, Wynnewood, PA 19096, USA
- 2Department of Cardiothoracic Surgery, University of Thessaly, Biopolis, 41110 Larissa, Greece
- 3Department of Surgery and Cancer, Hammersmith Hospital, Imperial College Healthcare NHS Trust, London W12 0HS, UK
- 4Department of Surgery, University of Milan, 20157 Milan, Italy
- 5Department of Thoracic Surgery, Cantonal Hospital Lucerne, 6000 Lucerne, Switzerland
Abstract
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.
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BibTeX
@article{magouliotis2026liquid,
title = {{Liquid Biopsy-Guided Surgical Decision-Making in Oligometastatic Non-Small Cell Lung Cancer: Toward Dynamic Risk Stratification in the Multidisciplinary Era}},
author = {Dimitrios E. Magouliotis and Vasiliki Androutsopoulou and Prokopis-Andreas Zotos and Namariq Abbaker and Ugo Cioffi and Fabrizio Minervini and Marco Scarci},
journal = {Cancers},
year = {2026},
month = oct,
doi = {10.3390/cancers18203338},
url = {https://www.mdpi.com/2072-6694/18/20/3338},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Liquid Biopsy-Guided Surgical Decision-Making in Oligometastatic Non-Small Cell Lung Cancer: Toward Dynamic Risk Stratification in the Multidisciplinary Era
AU - Dimitrios E. Magouliotis
AU - Vasiliki Androutsopoulou
AU - Prokopis-Andreas Zotos
AU - Namariq Abbaker
AU - Ugo Cioffi
AU - Fabrizio Minervini
AU - Marco Scarci
PY - 2026
DA - 2026/10/01
JO - Cancers
DO - 10.3390/cancers18203338
UR - https://www.mdpi.com/2072-6694/18/20/3338
AB - 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.
SN - 2072-6694
ER -