Progression Criteria for Cancer Antigen 15.3 and Carcinoembryonic Antigen in Metastatic Breast Cancer Compared by Computer Simulation of Marker Data

Abstract

We investigated the utility of computer simulation models for performance comparisons of different tumor marker assessment criteria to define progression or nonprogression of metastatic breast cancer. Clinically relevant values for progressive cancer antigen 15.3 and carcinoembryonic antigen concentrations were combined with representative values for background variations in a computer simulation model. Fifteen criteria for assessment of longitudinal tumor marker data were obtained from the literature and computerized. Altogether, 7200 different patients, each based on 50 measurements, were simulated. With a sampling interval of 4 weeks, the monitoring period for each event was approximately 3.8 years. Modulation of the background variation, the starting concentrations, and the cutoffs enabled identification of criteria that were robust against false-positive signals of progression. The computer simulation model is a fast, effective, and inexpensive approach for comparing the diagnostic potential of assessment criteria during clinically relevant conditions of steady-state and progressive disease. The model systems can be used to generate tumor marker assessment criteria for a variety of malignancies and to compare and optimize their diagnostic performance.