Harmonizing definitions in liquid biopsy: A terminology framework by the international society of liquid biopsy

The rapid expansion of liquid biopsy (LB) throughout the cancer care continuum is evidenced by the striking increase in annual publications, rising from approximately 100 per year in the early 2000s to more than 2200 in recent years. This exponential growth reflects the accelerating impact of LB across precision medicine. However, the field's evolution has been accompanied by inconsistent use of key terminology, creating barriers to clear communication, comparability of results, and appropriate clinical translation. To address this challenge, the International Society of Liquid Biopsy (ISLB) presents a comprehensive and harmonized terminology framework, an essential and timely effort to support the coherent advancement of the LB discipline. ISLB defines LB as the analysis of cells, nucleic acids, proteins, metabolites, and extracellular vesicles used to interrogate pathological or specific physiological conditions, obtained from bodily fluids, primarily through minimally invasive methods. Here we discuss relevant biospecimens, emphasizing their distinct sources and molecular characteristics. A central component of the manuscript is a rigorous clarification of analyte-specific terminology. This includes circulating free DNA and RNA (cfDNA, cfRNA), circulating tumor DNA and RNA (ctDNA, ctRNA), tumor fraction (TF), variant allele frequency (VAF), circulating tumor cells (CTCs), disseminated tumor cells (DTCs), circulating tumor microemboli (CTMs), extracellular vesicles (EVs), tumor-educated platelets (TEPs), soluble proteins, and metabolomic signatures. The manuscript also outlines the analytical methodologies, that enable sensitive detection of low-abundance tumor-derived signals. Clinical applications of LB in Oncology are defined across the disease continuum, including early cancer detection, molecular residual disease (MoRD) assessment, predictive biomarker evaluation, and tumor monitoring. By establishing a cohesive vocabulary, ISLB provides a robust reference framework that will evolve with scientific progress and guide the integration of LB into precision medicine.