Next-Generation Sequencing with Liquid Biopsies from Treatment-Naïve Non-Small Cell Lung Carcinoma Patients

SIMPLE SUMMARY: Screening for genomic alterations in treatment-naïve non-small cell lung carcinoma (NSCLC) is mainly done by tissue biopsy (TB), an invasive approach. However, it may not be possible to obtain a TB, the patient does not consent to it and/or the extracted nucleic acids are of poor quantity and/or quality for further genomic analyses, so a liquid biopsy (LB) is the only option to detect molecular target(s) for first-line treatment in these patients. However, a LB at diagnosis is still not often used in clinical centers since a TB is currently the gold standard approach for histological diagnosis, assessment of the PD-L1 status on tumor cells and evaluation of the molecular alterations. A number of different approaches are already available for the assessment of genetic abnormalities with LB, but next-generation sequencing (NGS) is the most promising. This review provides an overview of the main studies currently using LB NGS at diagnosis for NSCLC. We discuss its advantages and limitations in comparison with a TB and the perspectives for the future. ABSTRACT: Recently, the liquid biopsy (LB), a non-invasive and easy to repeat approach, has started to compete with the tissue biopsy (TB) for detection of targets for administration of therapeutic strategies for patients with advanced stages of lung cancer at tumor progression. A LB at diagnosis of late stage non-small cell lung carcinoma (NSCLC) is also being performed. It may be asked if a LB can be complementary (according to the clinical presentation or systematics) or even an alternative to a TB for treatment-naïve advanced NSCLC patients. Nucleic acid analysis with a TB by next-generation sequencing (NGS) is gradually replacing targeted sequencing methods for assessment of genomic alterations in lung cancer patients with tumor progression, but also at baseline. However, LB is still not often used in daily practice for NGS. This review addresses different aspects relating to the use of LB for NGS at diagnosis in advanced NSCLC, including its advantages and limitations.