Evaluation of serum CEA, CYFRA21-1 and CA125 for the early detection of colorectal cancer using longitudinal preclinical samples

TLDR

Blood‑borne biomarkers for early detection of colorectal cancer could markedly increase screening uptake. The study aimed to evaluate serum CEA, CYFRA21‑1, and CA125 for early detection of colorectal cancer in an asymptomatic cohort and to establish a baseline for developing biomarker panels that combine CEA to improve early detection. The authors conducted a nested case‑control study within UKCTOCS, measuring validated assays of CEA, CYFRA21‑1, and CA125 in 381 serial serum samples from 40 CRC patients, 20 benign cases, and 40 controls, and evaluated marker performance across pre‑diagnosis time groups. CEA showed modest sensitivity (25 % at 1 year and 13 % at 4 years with >5 ng/mL, rising to 57.5 % and 38.4 % with >2.5 ng/mL) and a 17–24‑month lead time, but CYFRA21‑1 and CA125 added no benefit, indicating CEA alone is insufficient as a screening tool.

Abstract

Blood-borne biomarkers for early detection of colorectal cancer (CRC) could markedly increase screening uptake. The aim of this study was to evaluate serum carcinoembryonic antigen (CEA), CYFRA21-1 and CA125 for the early detection of CRC in an asymptomatic cohort.This nested case-control study within UKCTOCS used 381 serial serum samples from 40 women subsequently diagnosed with CRC, 20 women subsequently diagnosed with benign disease and 40 matched non-cancer controls with three to four samples per subject taken annually up to 4 years before diagnosis. CEA, CYFRA21-1 and CA125 were measured using validated assays and performance of markers evaluated for different pre-diagnosis time groups.CEA levels increased towards diagnosis in a third of all cases (half of late-stage cases), whereas longitudinal profiles were static in both benign and non-cancer controls. At a threshold of >5 ng ml(-1) the sensitivities for detecting CRC up to 1 and 4 years before clinical presentation were 25% and 13%, respectively, at 95% specificity. At a threshold of >2.5 ng ml(-1), sensitivities were 57.5% and 38.4%, respectively, with specificities of 81% and 83.5%. CYFRA21-1 and CA125 had no utility as screening markers and did not enhance CEA performance when used in combination. CEA gave average lead times of 17-24 months for test-positive cases.CEA is elevated in a significant proportion of individuals with preclinical CRC, but would not be useful alone as a screening tool. This work sets a baseline from which to develop panels of biomarkers which combine CEA for improved early detection of CRC.