Diagnostic Accuracy of an Add-On, Blood-Based Screening Test for Colorectal Cancer in Two Established Screening Programmes

Background: CELTiC is a blood-based test consisting of a panel of four mRNAs (CEACAM6, LGALS4, TSPAN8 and COL1A2) associated with colorectal cancer (CRC). CELTiC has a high sensitivity (90%) for detecting advanced neoplasia (AN) when compared to faecal immunochemical test (FIT)-negative subjects. Aims: To evaluate the diagnostic accuracy of CELTiC as an add-on test following a positive FIT in two existing CRC screening programmes. Methods: We designed a prospective study in FIT-positive screenees. Analyses were performed in two (partially overlapping) groups: participants with FIT ≥ 47 μg Hb/g faeces (group I) and FIT ≥ 20 μg Hb/g faeces (group II). We estimated CELTIC sensitivity and specificity in detecting AN at a pre-defined and a post hoc threshold (targeted sensitivity: 90%). Results: We included 809 participants (n = 567 in group I and n = 486 in group II). CELTiC did not reach a sensitivity of 90% at the pre-defined threshold (Group I 41%, group II 27%). At the post hoc thresholds for 90% sensitivity in detecting AN, CELTiC had a specificity of 14% (53/388; 95% CI: 10% to 17%) in group I and 12% (44/354; 95% CI: 9% to 16%) in group II. Conclusions: In a FIT-positive population, CELTiC did not reach 90% sensitivity at the pre-defined threshold. At post hoc thresholds corresponding to 90% sensitivity, specificity was low. CELTiC cannot currently be recommended as an add-on test to detect AN in FIT-positive screenees in a CRC screening programme. Trial Registration: ClinicalTrials.gov identifier: NCT04980443, NCT05205967, NCT04369053.