First-Round Fecal Immunochemical Test Concentration Predicts Colorectal Cancer and Advanced Neoplasia in Second-Round Screening

Introduction: Enhancing fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening requires identifying additional predictive factors for colorectal neoplasia beyond current-round FIT concentration. We investigated whether first-round FIT concentration could predict colorectal neoplasia detection in the second screening round, using data from the randomized controlled trial Screening of Swedish Colons (SCREESCO). Methods: We conducted a cross-sectional analysis of SCREESCO FIT-arm participants with negative two-stool FIT (<10 μg Hb/g feces) in the first screening round, followed by a positive FIT (≥10 μg Hb/g feces) in the second round two years later with work-up colonoscopy. We used binary regression models to assess risk factors for colorectal neoplasia, including CRC and advanced colorectal neoplasia (ACN), at colonoscopy, according to participants’ characteristics and first- and second-round FIT concentrations. Results: In total, 1,991 individuals were included, with median FIT concentrations of 2.2 and 21.8 μg Hb/g feces in the first and second rounds, respectively. Higher first-round FIT concentration was associated with increased risks of CRC and ACN in the second round. Compared to those with first-round FIT concentrations of 0.0–1.9 μg Hb/g feces, the risk ratios for ACN were 1.38 (95% CI: 1.07–1.80) for 2.0–5.9 and 1.85 (95% CI: 1.38–2.48) for 6.0–9.9 μg Hb/g feces. For fixed second-round FIT concentration, the absolute risk of ACN increased in accordance with higher first-round FIT concentration. Discussion: Even an increase in low levels of FIT concentration is associated with future CRC and ACN detection. Combining first- and second-round FIT results could enhance the efficacy of screening. Trial registration: ClinicalTrials.gov number, NCT02078804.