Liquid Biopsy Found Effective at Capturing Genetic Alterations in NSCLC

Non–small-cell lung cancer (NSCLC) is a leading cause of death globally with a 26% 5-year survival rate. Chemotherapy and immunotherapy are mainstays of treatment, but the recent development of targeted therapy has improved patient outcomes. To test for actionable gene mutations, physicians have a number of tests available, including next-generation sequencing (NGS), a typical option as it provides more comprehensive sequencing than other molecular testing options. The National Comprehensive Cancer Network, the European Society for Medical Oncology, the American Society of Clinical Oncology, and the International Association for the Study of Lung Cancer all recommend broad molecular profiling for first-line therapy and for some types of progression to detect resistance. Tumor tissue is used for NGS to identify biomarkers in NSCLC, but it is not without limitations. Invasive procedures are necessary to obtain the tissue, some tumors are in inaccessible sites, and there may be insufficient tissue sample left after pathology examination. In addition, tissue samples can have limitations in capturing heterogeneity of the tumor.

Liquid biopsy uses circulating tumor DNA, which is shed from the tumor usually in response to cell death and is a viable alternative to tumor tissue for NGS. Liquid biopsy has several advantages over tissue biopsy including minimal invasiveness, more rapid turnaround time due to less sample preparation, and the ability to capture broad tumor heterogenicity. The use of liquid biopsy in metastatic NSCLC testing has increased dramatically.

In a recent study, liquid biopsy was evaluated for use in patients diagnosed with stage IV NSCLC in the first-line setting to illustrate that it can be a standard decision-making tool. The study was a retrospective analysis of 170 patients with metastatic NSCLC without prior treatment who had both tissue and liquid biopsy NGS. Treatment decisions were based on liquid biopsy results 73.5% of the time. Liquid biopsy NGS showed higher testing success and had an average 26.8-day faster return than tissue testing. When guideline-recommended biomarkers were evaluated, liquid biopsy had 94.8% to 100% concordance with tissue biopsy and identified guideline-recommended biomarkers in 76.5% of patients versus 54.9% of patients with tissue biopsy. Survival outcome and time to treatment were not significantly different between liquid biopsy and tissue biopsy in these patients.

Source: Raez LE, Brice K, Dumais K, et al. Liquid biopsy versus tissue biopsy to determine front line therapy in metastatic non-small cell lung cancer (NSCLC). Clin Lung Cancer. 2023;24(2):120-129.