Is Negative Fecal Immunochemical Test Reassuring? The Cumulative Risk of Colorectal Cancer after Multiple Negative...

Colorectal cancer (CRC) risk is approximately 0.1% according to registry data, and fecal immunochemical tests (FITs) identify approximately 5% of screened individuals as positive. We evaluated whether a negative FIT result is reassuring regarding CRC risk.

In this retrospective cohort study, 141,982 Taiwanese individuals aged ≥50 who underwent self-paid medical screening from 1994 to 2008 were enrolled. CRC cases and all-cause deaths were identified through the National Cancer Registry and National Death File. A negative FIT was defined as <20 μg Hb/g.

There were 987 CRC patients with a negative FIT and 713 with a positive FIT. Among the 133,369 individuals with one negative FIT, 113 CRC patients were registered within 2 years and 803 within 10 years; only 15% of the CRC cases were identified within the first 2 years after testing. The overall incidence was 1.27/1,000 person-years, decreasing by 63% to 0.80/1,000 person-years after one negative FIT. With repeated biennial negative FITs, CRC risk declined to 63%, 53%, 33%, 23%, and 10% over 10 years. All-cause mortality decreased from 1,106/100,000 person-years to 511/100,000 person-years. Notably, 84% of the cohort had consistently negative FIT results across all five rounds.

Two-thirds of the 10-year CRC risk remained in individuals following one negative FIT. The risk after a negative FIT result reemerged 2 years after testing, highlighting the importance of continuing biennial FIT screening. Consistently negative FITs were associated with reduced CRC risk and a lower all-cause mortality. This study is limited by the lack of confirmatory colonoscopy in FIT-negative individuals, which may lead to an underestimation of CRC incidence.