Elucidating Higher FIT Interval Caners in Proximal than Distal Colon: Population-Based Periodical Screening Cohort Design

Abstract

Background: The risk of fecal immunological test (FIT) interval cancer (IC) is higher in the proximal colon than the distal colon but the underlying mechanism explaining the disparity remains elusive. Therefore in this study, we aimed to investigate whether the disparity is attributed to FIT accuracy or the fast progression rates from early to late stage (upstaging) within preclinical-detectable phase (PCDP) and from PCDP to clinical phase (CP). Methods: We did a population-based periodical screening cohort study. Data derived from Taiwanese nationwide colorectal cancer (CRC) organized service screening program. A total of 5,417,699 eligible population aged 50-69 with 3,074,538 individuals ever attending until the end of 2014. The incidence rate of entering the PCDP, the upstaging rate within PCDP, the rate of surfacing to CP, and the test sensitivity classified by early (stage 0/I) and late (stage 2+) stage analyzed with the five-state Markov model. Findings: The proportions of ICs (19% vs 16%) and late CRCs (76% vs 67%) were higher in the proximal colon than the distal colon, which was caused by a faster progression rate from PCDP to CP by 19% and a higher likelihood of upstaging in the proximal colon than the distal colon by 1.6-fold, resulting in the corresponding survival difference of IC, but not site-specific FIT accuracy. Interpretation: Faster progression noted in proximal colon not only supports the previous evidence on rapid transition from dysplasia to malignancy for sessile serrated adenomas but also explain the disparity of effectiveness of FIT and provide a new insight into precision medicine for identifying those who are susceptible to the proximal IC of CRC. Funding: None Declaration of Interests: All authors declare no competing interests. Ethics Approval Statement: This study was approved by the Health Promotion Administration, Ministry of Health and Welfare prior to data retrieval and analysis (A1081113) of Taiwanese government and approved by the Research Ethics Committee of National Taiwan University Hospital prior to data collection pursuant to the regulation of the Institutional Review Board (20192023W).