Clinical utility of personalized reference intervals for CEA in the early detection of oncologic disease

Abstract Objectives Personalized reference intervals (prRI) have been proposed as a diagnostic tool for assessing measurands with high individuality. Here, we evaluate clinical performance of prRI using carcinoembryonic antigen (CEA) for cancer detection and compare it with that of reference change values (RCV) and other criteria recommended by clinical guidelines (e.g. 25 % of change between consecutive CEA results (RV25) and the cut-off point of 5 μg/L (CP5)). Methods Clinical and analytical data from 2,638 patients collected over 19 years were retrospectively evaluated. A total 15,485 CEA results were studied. For each patient, we calculated prRI and RCV using computer algorithms based on the combination of different strategies to assess the number of CEA results needed, consideration of one or two limits of reference interval and the intraindividual biological variation estimate (CV I ) used: (a) publicly available (CV I-EU ), (b) CV I calculated using an indirect method (CV I-NOO ) and (c) within-person BV (CV P ). For each new result identified falling outside the prRI, exceeding the RCV interval, RV25 or CP5, we searched for records identifying the presence of tumour at 3 and 12 months after the test. The sensitivity, specificity and predictive power of each strategy were calculated. Results PrRI approaches derived using CV I-EU , and both limits of reference interval achieve the best sensitivity (87.5 %) and NPV (99.3 %) at 3 and 12 months of all evaluated criteria. Only 3 results per patients are enough to calculate prRIs that reach this diagnostic performance. Conclusions PrRI approaches could be an effective tool to rule out new oncological findings during the active surveillance of patients.