Plasma genotyping in patients with non-small-cell lung cancer: simplifying or confusing the diagnosis?

The identification of driver mutations in patients with advanced non-small-cell lung cancer has changed the treatment outcomes for patients with actionable driver mutations. Lack of tissue at diagnosis, however, remains a central obstacle in making optimal treatment decisions in patients with advanced disease. Although the US FDA has approved one plasma-based test for detecting epidermal growth factor receptor mutations in patients with advanced stage disease, sensitivity of these assays remains mediocre, necessitating additional tissue testing and possible delays in patients with negative results. Serial monitoring for response and early detection of acquired resistance to targeted therapies is also possible with cell-free DNA, however the benefit of switching therapy prior to detection of changes on imaging is unknown currently.