Liquid Biopsy for Advanced NSCLC: A Consensus Statement From the International Association for the Study of Lung Cancer
Open accessAbstract
Although precision medicine has had a mixed impact on the clinical management of patients with advanced-stage cancer overall, for NSCLC, and more specifically for lung adenocarcinoma, the advances have been dramatic, largely owing to the genomic complexity and growing number of druggable oncogene drivers. Furthermore, although tumor tissue is historically the "accepted standard" biospecimen for these molecular analyses, there are considerable innate limitations. Thus, liquid biopsy represents a practical alternative source for investigating tumor-derived somatic alterations. Although data are most robust in NSCLC, patients with other cancer types may also benefit from this minimally invasive approach to facilitate selection of targeted therapies. The liquid biopsy approach includes a variety of methodologies for circulating analytes. From a clinical point of view, plasma circulating tumor DNA is the most extensively studied and widely adopted alternative to tissue tumor genotyping in solid tumors, including NSCLC, first entering clinical practice for detection of EGFR mutations in NSCLC. Since the publication of the first International Association for the Study of Lung Cancer (IASLC) liquid biopsy statement in 2018, several additional advances have been made in this field, leading to changes in the therapeutic decision-making algorithm for advanced NSCLC and prompting this 2021 update. In view of the novel and impressive technological advances made in the past few years, the growing clinical application of plasma-based, next-generation sequencing, and the recent Food and Drug and Administration approval in the United States of two different assays for circulating tumor DNA analysis, IASLC revisited the role of liquid biopsy in therapeutic decision-making in a recent workshop in October 2020 and the question of "plasma first" versus "tissue first" approach toward molecular testing for advanced NSCLC. Moreover, evidence-based recommendations from IASLC provide an international perspective on when to order which test and how to interpret the results. Here, we present updates and additional considerations to the previous statement article as a consensus from a multidisciplinary and international team of experts selected by IASLC.
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A growing body of evidence shows many clinical uses for ctDNA in adults with solid tumors, from prognostication and minimal residual disease evaluation to detection of targetable alterations.
“There is a growing body of data demonstrating numerous clinical applications for ctDNA in adults with solid tumors, ranging from prognostication and evaluation of minimal residual disease (MRD) to detection of targetable alterations.7–12”
From Clinical Liquid Biopsy Testing for Detection of Actionable Genomic Alterations in Children and Young Adults With Advanced Solid Tumors on the GAIN Study (2026) · cites this paper as [8]
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Self-citation
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Pascual, J., Attard, G., Bidard, F.-C., Curigliano, G., De Mattos-Arruda, L., Diehn, M., Italiano, A., Lindberg, J., Merker, J. D., Montagut, C., et al. (2022) · Annals of Oncology · doi:10.1016/j.annonc.2022.05.520 · Cited by 783 · see citing works
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- Authors
- Rolfo, C., Mack, P., Scagliotti, G. V., Aggarwal, C., Arcila, M. E., Barlesi, F., Bivona, T., Diehn, M., Dive, C., Dziadziuszko, R., Leighl, N., Malapelle, U., Mok, T., Peled, N., Raez, L. E., Sequist, L., Sholl, L., Swanton, C., Abbosh, C., Tan, D., Wakelee, H., Wistuba, I., Bunn, R., Freeman-Daily, J., Wynes, M., Belani, C., Mitsudomi, T., & Gandara, D.
- Affiliations
- Tisch Cancer Institute (US)
- Ospedale San Luigi Gonzaga (IT)
- University of Pennsylvania (US)
- Memorial Sloan Kettering Cancer Center (US)
- University of California, San Francisco (US)
- Stanford Medicine (US)
- Cancer Research UK (GB)
- University of Toronto (CA)
- University of Naples Federico II (IT)
- Chinese University of Hong Kong (HK)
- Soroka Medical Center (IL)
- Florida International University (US)
- Massachusetts General Hospital (US)
- Brigham and Women's Hospital (US)
- The Francis Crick Institute (GB)
- National University of Singapore (SG)
- The University of Texas MD Anderson Cancer Center (US)
- International Association for the Study of Lung Cancer (US)
- Pennsylvania State University (US)
- Kindai University (JP)
- University of California Davis Medical Center (US)
- Corresponding author
- Gandara, David
- ORCID
- Rolfo, Christian
- Mack, Philip
- Scagliotti, Giorgio V.
- Aggarwal, Charu
- Arcila, Maria E.
- Bivona, Trever
- Diehn, Maximilian
- Dive, Caroline
- Leighl, Natasha
- Malapelle, Umberto
- Mok, Tony
- Peled, Nir
- Raez, Luis E.
- Sequist, Lecia
- Sholl, Lynette
- Swanton, Charles
- Tan, Daniel
- Wakelee, Heather
- Wistuba, Ignacio
- Belani, Chandra
- Mitsudomi, Tetsuya
- Gandara, David
- Venue
- Journal of Thoracic Oncology
- Publisher
- Elsevier BV
- Published
- 2021-10
- Volume
- 16
- Issue
- 10
- Pages
- 1647-1662
- ISSN
- 1556-0864 (ISSN-L)
- OpenAlex
- W3178692152
- Cited by
- 683
- References
- 124
- Citations by year
- 2026: 118 · 2025: 154 · 2024: 130 · 2023: 151 · 2022: 111 · 2021: 19
- FWCI
- 66.95
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Thoracic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Funders
- GlaxoSmithKline
- Merck
- Royal Society
- Novartis
- Cancer Research UK
- Roche
- European School of Oncology
- EMD Serono
- Mirati Therapeutics
- ANGLE
- Amgen
- Bristol-Myers Squibb (.16/347,134, WO2017181202A2)
- Eli Lilly and Company
- Astex Pharmaceuticals
- Pfizer
- Clovis Oncology
- AstraZeneca
- Bayer Fund
- Genentech
- Les Laboratories Pierre Fabre
- ACEA Biosciences
- National Institutes of Health
- Stand Up To Cancer
- National Cancer Institute (EcoR1)
- Merck Sharp and Dohme
- Boehringer Ingelheim
- Francis Crick Institute
- Intel Corporation
- Exelixis
- Janssen Pharmaceuticals
- Stanford University
- International Association for the Study of Lung Cancer
- Celgene
- Meso Scale Diagnostics
- Takeda Pharmaceuticals U.S.A.
- Daiichi-Sankyo
- Eisai
- Gilead Sciences
- European Society for Medical Oncology
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Treatments and Mutations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
- Keywords
- liquid biopsy, non-small cell lung cancer, lung adenocarcinoma, circulating tumor DNA, targeted therapy selection, EGFR mutation, next-generation sequencing
- MeSH terms
- Liquid Biopsy, Carcinoma, Non-Small-Cell Lung, Humans, Lung Neoplasms, Oncogenes, Consensus
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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