Association Between Concentrations of Hemoglobin Determined by Fecal Immunochemical Tests and Long-term Development of Advanced Colorectal Neoplasia

Abstract

Background & Aims Colorectal cancer (CRC) screening using quantitative fecal immunochemical tests (FITs) is rapidly gaining ground worldwide. FITs are invariably used in a dichotomous manner using pre-specified cut-off values. To optimize FIT-based screening programs, we investigated the association between fecal hemoglobin (fHb) concentrations below the FIT cut-off value and later development of colorectal advanced neoplasia (AN). Methods We analyzed data collected from a population-based study of 9561 average-risk subjects (50–74 years old) in the Netherlands who were offered 4 rounds of FIT screening for CRC from November 2006 through December 2014. We analyzed data from 7663 participants screened at least once and found to have a negative FIT result at baseline (below the cut-off value of 10 μg Hb/ g feces). Participants were followed for a median of 4.7 years (interquartile range, 2.0–6.1 years); CRCs diagnosed outside the screening program were identified from the Dutch Comprehensive Cancer Centre database. Hazard ratios for AN were determined using Cox proportional hazard regression analyses. Logistic regression techniques were used to calculate risks of AN after consecutive fHb concentrations below the cut-off value. Results After 8 years of follow-up, participants with baseline concentrations of 8–10 μg fHb/g had a higher cumulative incidence of AN (33%) than participants with 0 μg fHb/g (5%) (P