CYFRA 21-1 as a circulating biomarker in non-small cell lung cancer

CYFRA 21-1, a fragment of cytokeratin 19, is a circulating biomarker that reflects epithelial cell turnover. Beyond its association with malignancy, CYFRA 21-1 may also serve as an indicator of epithelial injury and inflammation, which can be relevant in non-cancer clinical contexts, complicating its interpretation. Its measurement can be performed using automated immunoassays, making it a valuable laboratory tool for non-small cell lung cancer (NSCLC). We provide an overview of immunoassay principles and platform differences, calibration/traceability, analytical sensitivity and imprecision, and the effect of non-harmonization between the methods. To ensure the correct interpretation of the results, key pre-analytical requirements (specimen type, handling, and stability) and confounders (renal impairment, benign pulmonary disease, inflammatory conditions, and assay interference) that can impact the concentrations are mentioned. There is published evidence that supports CYFRA 21-1 in supplementary diagnostic assessment, prognostic stratification, and, most consistently, longitudinal monitoring. Serial values measured relative to biological and analytical variations can indicate treatment response and an early relapse of CYFRA 21-1. We propose practical solutions for laboratory reporting and ordering challenges, including the integration of imaging and tissue diagnostics, preference for within-platform serial monitoring, and use of interpretive comments, all aimed at ensuring quality assurance and assay harmonization. Serum CYFRA 21-1 can be utilized in practical laboratory use of NSCLC by including standardized measurement, a locally verified decision limit, interpretation based on context with incorporation of stage and histology, and other biomarkers.