Clinical equivalence of two cytokeratin markers in non-small cell lung cancer - A study of tissue polypeptide antigen and cytokeratin 19 fragments

Study objectives: We have longstanding experience with tissue polypeptide antigen (TPA), a tumor marker of the cytokeratin (CK) family. In the mid-1990s, a new CK marker, CK 19 fragments (CYFRA 21-1), became popular and widely accepted. This is the first study, specifically designed to compare the two markers. Design: Analysis of a single institution database over a 3-year period (ie, 1998 to 2000). Setting: Community-based hospital and second referral level institution for a province of 500,000 people. Patients: The study included 180 new consecutive patients (M men) with pathologically documented non-small cell lung cancer (NSCLC), who were observed during and after treatment, and eventually were assessed for status. Interventions: Anthropometric, clinical, and laboratory data, including TPA and CYFRA 21-1 serum levels, were recorded prospectively. Standard nonparametrie tests, Kaplan-Meyer survival analyses, Cox proportional hazards models, receiver-operating characteristic (ROC) curves, and estimates were used for statistical analysis. Measurements and results: A total of 1,299 twin TPA and CYFRA 21-1 serum assays (180 performed at diagnosis and 1,119 performed during or after treatment) were obtained. Intermarker correlation tests revealed incredibly high Spearman p indexes, ranging from 0.935 at diagnosis to 0.813 to 0.921 at the different follow-up times. The substantial equivalence of the two tests explained all the other results, as follows: their similar profile of correlation with the other variables (objective treatment response: TPA rho, 0.456; CYFRA 21-1 rho, 0.463; follow-up performance status: p range, 0.424 to 0.435); their superimposable capability to predict important clinical situations (eg, recognizing a metastatic disease at diagnosis with areas under the ROC,curve of 0.742 and 0.706, respectively); their nearly identical prognostic significance (the D statistic of the goodness-of-fit of a multivariate survival model: TPA, 851.0; CYFRA 21-1, 851.6). Conclusions: In most of their traditional clinical applications the two serum tests are equivalent because of their virtual identity. We strongly recommend using a CK test in the evaluation of each NSCLC patient. The choice between TPA and CYFRA 21-1 can be based on nonclinical factors, such as the laboratory experience or preference, and the cost of the two kits.