Biological variation and analytical imprecision of CA 125 in patients with ovarian cancer.

Despite the availability of serial data on CA 125 in ovarian cancer, the problem of interpreting a change over time is still unsolved. Changes in marker concentrations are due not only to patients improving or deteriorating but also to analytical imprecision and normal intra-individual biological variation. The aim of this study was to assess the analytical imprecision (CV(A)) and the intra- and inter-individual biological variation (CV(I) and CV(G), respectively) of CA 125 in a group of 26 patients with clinically stable ovarian cancer. Furthermore, the critical difference for a change between two consecutive CA 125 concentrations calculated as square root(2) x Z x (CV(A)2 + CV(I)2)(1/2) (Z =1.65 for unidirectional and 1.96 for bidirectional changes, p < or = 0.05) and the index of individuality calculated as ((CV(A)2+CV(I)2)/CV(G)2)(1/2) were estimated. After the exclusion of outliers, CV(A) and the average CV(I) and CV(G) were 12.1%, 24.0%, and 43.1%, respectively. The index of individuality was 0.62 and the critical difference calculated for unidirectional changes was 62.6%. CV(A) and CV(I) contribute considerably to the variation in serial results and should, therefore, be included in the criteria for serum tumor marker assessment during monitoring of patients with ovarian cancer. The cut-off value of CA 125 is of minor value in detecting unusual results for an individual subject, when previous measurements from an individual are available. These measurements should be preferred as reference for interpretation of new results.