Clinical Validation pf a Multi Target Fecal Immunochemical Test for Colorectal Cancer Screening

Aims The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening. However, FIT leaves room for improvement, in particular for detecting advanced adenomas. To this end the present study aims to design a multi target FIT (mtFIT) to improve FIT-based screening.

Methods Individuals (n = 1284) were classified by the most advanced lesion detected during colonoscopy: 47 CRC, 135 advanced adenoma, 30 advanced serrated polyp, 250 non-advanced adenoma, 53 non-advanced serrated polyp and 769 controls. Antibody-based assays were developed for nine previously identified biomarkers and applied to left-over FIT material. Classification And Regression Tree (CART) analysis was used to identify the optimal combination of these biomarkers and the results were cross-validated to correct for over-optimism. Performance of the mtFIT was compared to FIT, at the same specificity, and impact on population level was projected using the Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) screening model.

Results CART analysis of biomarker levels yielded hemoglobin, calprotectin and serpin family F member 2 to construct the mtFIT. At equal specificity of 96.6 %, sensitivity for advanced neoplasia increased from 37.3 % (95 % CI 30.7-44.2) with FIT to 48.1 % (95 % CI 41.2-55.1) with mtFIT. In particular, sensitivity for advanced adenomas rose by 60.5 % (cross-validation 34.5 %). mtFIT-based screening was predicted to decrease CRC mortality by 11.1 % (cross-validation 6.2 %) compared to FIT-based screening. mtFIT-based screening would be cost-effective at mtFIT test costs below €72 (cross-validation €52) assuming a willingness-to-pay threshold of once the Dutch gross domestic product per capita of €41,258 per life-year gained.

Conclusions Accuracy of the mtFIT for detecting advanced neoplasia was higher compared to FIT, especially for advanced adenomas. Moreover, mtFIT-based screening appeared to be more effective and cost-effective compared to the current FIT program. Validation of its improved test performance will be examined in a prospective screening trial, which is currently in preparation.

Citation: de Klaver W, Wisse P, van Wifferen F etal. eP252 CLINICAL VALIDATION OF A MULTI TARGET FECAL IMMUNOCHEMICAL TEST FOR COLORECTAL CANCER SCREENING. Endoscopy 2021; 53: S180.

Publication History

Article published online:
19 March 2021