Critical issues in the clinical application of liquid biopsy in non-small cell lung cancer

On the road from the laboratory bench to the patient’s bedside, an assay measuring a tumor marker must be evaluated in order to demonstrate its analytic and clinical validity (respectively: the assay accuracy and reproducibility, and its ability to identify a biologic difference that predicts patient outcome), and at the end its clinical utility (the results of the assay—positive or negative—lead to a clinical decision that evidently improves patient outcome) (1). Thus, a tumor marker must encompass several levels of evidence in order to demonstrate its clinical utility, with the final aim to improve patient outcome, in terms of overall survival (OS), disease-free survival and quality of life, and obtain a more cost-efficient application of effective therapies. The Tumor Marker Utility Grading System (TMUGS) is a framework that establishes an agenda for evaluating the clinical utility of tumor markers, and describes five levels of evidence as “categories that define the quality of data available on which the utility score is based”. These levels range from the weak level V evidence, derived from case reports and clinical examples, to the strongest level I evidence, “the definitive demonstration of clinical utility, obtained by a single, high-powered, prospective, randomized, controlled trial or from a meta-analysis or overview of multiple, well-designed studies”, passing through intermediate degrees of evidence in levels II–IV (2)