Risk of cancers proximal to the colon in fecal immunochemical test positive screenees in a colorectal cancer screening program

Abstract

In more than half of the colorectal cancer (CRC) screening participants with a positive fecal immunochemical test (FIT) result, no advanced neoplasia (AN) is detected at colonoscopy. The positive FIT result could also be generated by cancers located proximal to the colon: upper gastrointestinal, oral cavity, nose and throat cancers. We evaluated screenees' risk of being diagnosed with a cancer proximal to the colon within the three years and compared risks between those with a positive versus those with a negative FIT. Data of Dutch CRC screening participants who underwent biennial FIT-based screening 2014-2018 were collected from the national screening database and linked to the National Cancer Registry. Screenees were classified into three groups: FIT-positives with AN (FIT+/AN+), FIT-positives without AN (FIT+/AN-) and FIT-negatives (FIT-). We compared the cumulative incidence of cancers proximal to the colon in each group three years after FIT. A Cox regression analysis with left truncation and right censoring, using FIT positivity as time-dependent variable and stratified for sex, was performed to compare the hazard of cancers proximal to the colon in FIT-positives versus FIT-negatives. Three-year cumulative incidence of cancers proximal to the colon in FIT+/AN+ (n=65,767), FIT+/AN- (n=50,661) and FIT- (n=1,831,647) screenees was 0.7%, 0.6% and 0.4%, respectively (p<0.001). FIT-positives were older and more frequently male than FIT-negatives (p<0.001). Significantly more cancers proximal to the colon were detected among FIT-positives (p<0.001; hazard ratio 1.55, 95% CI: 1.44 to 1.67). FIT-positive screenees were at significantly increased risk of being diagnosed with a cancer proximal to the colon within three years after FIT, though the three-year cumulative incidence was still less than one percent.