Impact of a higher fecal immunochemistry test cut-off on pathology detected in subsequent rounds of a colorectal screening program

Background and Aims Fecal immunochemical test (FIT)–based colorectal cancer (CRC) screening is superior to the traditional binary fecal occult blood test. Its quantitative nature allows the investigator to choose a positivity threshold to match cost and endoscope capacity. The optimal threshold is still debated. BowelScreen, the Irish national colorectal cancer screening program, has a cut-off of 45 μg Hb/g feces, and in this study we investigated the impact of this threshold on pathology detected in round 2 in individuals who had a negative result for round 1 FIT (FIT 1 ). Methods All individuals with a negative FIT 1 result who completed a round 2 FIT (FIT 2 ) 2 years later were included. Pathology outcomes for individuals who had positive FIT 2 results were correlated with FIT 1 levels. Results A total of 37,877 individuals had negative FIT 1 results and completed FIT 2 . One thousand two hundred thirty (3.2%) had positive FIT 2 results (702 men [57%], median age 69, age range 60-70 years). Quantitative analysis showed that at an FIT 1 level  2 results. At a higher cut-off of 40.1 to 45 μg Hb/g feces, 15.6% of individuals had positive FIT 2 results. One thousand two (81.5%) underwent colonoscopy, with clinical outcomes in all cases. Three hundred fifty-one (35%) had normal colonoscopy results. The proportion of individuals with normal colonoscopy results decreased as FIT 1 levels rose. Conversely, advanced pathology (CRC + high-risk adenomas) rates rose from 7% to 50% when FIT 1 was  1 results (22 stage I, 12 stage II, 14 stage III, 3 stage IV). All 3 stage IV individuals had FIT 1 results  Conclusions Varying rates of pathology are observed in round 2 of a screening program based on the quantitative level of a negative round 1 FIT result when the positivity threshold is relatively high. A CRC rate of 5.1% within this group appears acceptable. Although patients with incurable cancer were observed, the positivity threshold to capture these cases within round 1 would have been so sensitive that it would create an unsustainable endoscopy referral burden.