Introduction
The quantitative fecal immunochemical test (FIT) is widely used for colorectal cancer (CRC) screening. While the association between FIT concentration and the risk of advanced colorectal neoplasia (ACN) detection is well established, the predictive performance of current-round FIT concentration alone has limitations. Identifying additional predictive factors could enhance screening. For individuals with a prior colonoscopy, colonoscopy findings and quality metrics may serve as such factors.1 For those who did not undergo colonoscopy due to a negative FIT in the previous round, alternative predictors should be explored. We hypothesized that prior-round FIT concentration could serve as a potential predictor.
Aims & Methods
We aimed to investigate whether prior-round negative FIT concentration could predict CRC and ACN detection by conducting a cross-sectional analysis of data from the FIT arm of the SCREESCO, a nationwide randomized controlled trial on CRC screening in Sweden.1,2 A sample of the Swedish population aged 60 years was randomly assigned to one of three arms: the once-colonoscopy arm, FIT arm, or control arm. Individuals in the FIT arm were invited to undergo two rounds of quantitative FIT screening in the first and third years. A highly sensitive method was used to assess FIT positivity, with a cut-off concentration of ≥10 μg Hb/g feces. We estimated the detection rates of CRC and ACN in second-round colonoscopy based on first-round FIT concentration. Binary regression models were used to assess whether first-round FIT concentration was associated with CRC and ACN detection in the second round. The models included participant characteristics such as sex, body mass index, and smoking status, and second-round FIT concentration, in addition to first-round FIT concentration.
Results
A total of 1,991 individuals were included, with a median FIT concentration of 2.2 μg Hb/g feces (interquartile range: 0.4–4.6) in the first round and 21.8 (13.4–50.8) in the second round. CRC and ACN were detected during second-round colonoscopy in 23 (1.2%) and 267 (13.4%) individuals, respectively. Individuals with first-round FIT concentration of 0–1.9, 2.0–5.9, and 6.0–9.9 μg Hb/g feces had second-round CRC detection rates of 0.8%, 0.9%, and 2.6%, respectively, and ACN detection rates of 9.7%, 12.5%, and 15.9%, respectively. A higher first-round FIT concentration was associated with an increased risk of CRC (risk ratio per unit increase 1.27; 95% confidence interval 1.10–1.47) and ACN (1.08; 1.04–1.12) detection in the second round, after adjusting for the second-round FIT concentration and participant characteristics. For a fixed second-round FIT concentration, the absolute risk of second-round ACN detection increased with higher first-round FIT concentration. For instance, in a nonsmoking or ex-smoking male with a second-round FIT concentration of 20 µg Hb/g feces, the risk increased from 10.0% at < 0.2 µg Hb/g feces in the first round to 14.9% at 5 µg Hb/g feces and 19.6% at 9.9 µg Hb/g feces.
Conclusion
First-round negative FIT concentration is predictive of CRC and ACN detection in the second screening round. Even an increase in low levels of the FIT concentration is associated with future detection of these neoplasms. Incorporating first-round FIT concentration alongside second-round FIT concentration may enhance risk stratification in CRC screening, leading to more efficient use of colonoscopy resources.
References
1. Sekiguchi M, Westerberg M, Löwbeer C, Forsberg A. Gastrointest Endosc. 2025 Feb 4. doi: 10.1016/j.gie.2025.01.037. Epub ahead of print.
2. Forsberg A, Westerberg M, et al. Lancet Gastroenterol Hepatol. 20227: 513-21. doi: 10.1016/S2468-1253(21)00473-8.