Risk factors associated with false-positive fecal immunochemical test results in colorectal cancer screening.

In more than half of the colorectal cancer 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 3 years and compared risks between those with a positive vs those with a negative FIT. Data of Dutch colorectal cancer 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 3 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 3 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 participants who were FIT-positive vs FIT-negative. 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 < .001). FIT-positives were older and more frequently male than FIT-negatives (P < .001). Significantly more cancers proximal to the colon were detected among FIT-positives (P < .001; hazard ratio, 1.55; 95% CI, 1.44-1.67). FIT-positive screenees were at significantly increased risk of being diagnosed witha cancer proximal to the colon within 3 years after FIT,although the 3-year cumulative incidence was still less than 1%.

COVID-19: An Opportunity to Reimagine Colorectal Cancer Diagnostic Testing—A New Paradigm Shift

Mo1177 Participation, FIT-Result and Yield in Three Rounds of Biannual FIT-Based Screening in the Netherlands

Quantitation of Hemoglobin Improves Fecal Immunochemical Tests for Noninvasive Screening

Background: The current guideline does not recommend upper gastrointestinal evaluation for patients with a positive fecal immunochemical test (FIT) and negative colonoscopy results. However, this indication was based on low-quality evidence as data on this issue are very limited. We assessed the risk of proximal cancers (oral or throat, esophageal, stomach, and small intestine cancers) after negative or positive FIT results in the Korean National Cancer Screening Program (NCSP). Methods: Using the NCSP databases, we collected data on participants who underwent FIT between 2009 and 2011. Participants were classified based on FIT results and colorectal cancer (CRC) diagnosed within 1 year after FIT as FIT− (n = 5,551,755), FIT+/CRC− (n = 368,553), and FIT+/CRC+ (n = 12,236). Results: The incidence rates of overall proximal cancers in FIT−, FIT+/CRC−, and FIT+/CRC+ patients within 1, 2, and 3 years after FIT were 0.38%, 0.68%, and 2.26%; 0.57%, 0.93%, and 2.74%; and 0.79%, 1.21%, and 3.15%, respectively. After adjusting confounding variables, the risks of esophageal, stomach, and small intestine cancers as well as overall proximal cancers within 1, 2, and 3 years after FIT were higher in FIT+/CRC− patients than those in FIT− patients. However, the risk of oral or throat cancer did not differ between FIT− and FIT+/CRC− patients. The risks for oral or throat cancer and small intestine cancer were higher in FIT+/CRC+ patients than those in FIT+/CRC− patients. Conclusions: In this population-based study, FIT+/CRC− patients were at higher risk for esophageal, stomach, and small intestine cancers than were FIT− patients, suggesting that positive FIT results were associated with these cancers.

Background:Early colorectal cancer (CRC) detection helps reduce the mortality rate. This study aimed to investigate colon lesions in individuals with positive and negative fecal immunochemical test (FIT) results among the (PERSIAN) Guilan cohort study (PGCS) population.Methods:This cross-sectional study was conducted on 1158 participants over 50 who were volunteers for the FIT stool test at the Endoscopy Department of Razi Hospital, Rasht, Iran, from 2021 to 2022. The FIT test was screened for all participants, and for 172 individuals (86 individuals from each group with positive and negative FIT results), a colonoscopy was performed to investigate the colon lesions. Demographic/clinical characteristics, FIT results, colonoscopy findings, and the Bristol Stool Chart were completed. All data were analyzed using SPSS Version 16, considering a significant level<0.05.Results:Out of 1,158 participants, 86 had positive FIT results, and 172 (52.3%) were females. The colonoscopy results showed that 34.3% of the patients had colon lesions. Individuals with positive FIT exhibited a significantly higher prevalence of colon lesions (p<0.001). No statistically significant differences were observed between positive and negative FIT results, demographic and clinical characteristics, and the location of lesions in individuals with colon lesions (p>0.05). Moreover, there was a significant difference in pathological findings and the presence of adenomatous polyps regarding the FIT results (p<0.001).Conclusion:The effectiveness of FIT in the initial stages of screening for early lesion detection is considerable, especially for individuals with upper age.

A Quarter of Participants With Advanced Neoplasia Have Discordant Results From 2-Sample Fecal Immunochemical Tests for Colorectal Cancer Screening

The participation in the FIT-based colorectal cancer screening programme and subsequent compliance to colonoscopy after a positive FIT test was only slightly affected during the COVID-19 pandemic in Denmark.

ObjectiveTo explore the performance of a protocol combining fecal immunochemical test (FIT) and a high-risk factor questionnaire (HRFQ) for selecting patients requiring colonoscopy as part of a population-based colorectal cancer (CRC) screening program in China.MethodsFrom 2015 to 2016, we conducted a CRC screening program for all residents aged 45 years or older in Tianhe District, Guangzhou City, China. Participants underwent an FIT and received an HRFQ as part of primary screening. Those with positive FIT and/or HRFQ results were considered to be at high risk and were recommended to undergo colonoscopy.ResultsA total of 10 074 subjects were recruited and enrolled in the screening program. In the enrolled population, 17.5% had positive FIT results and 19.4% had positive HRFQ results. Of those recommended to undergo diagnostic colonoscopy, 773 did so. The screening method’s overall positive predictive value (PPV) was 4.9% for non-adenomatous polyps, 11.4% for low-risk adenomas (LRAs), 15.9% for high-risk adenomas (HRAs) and 1.6% for CRC. The PPVs of positive FIT results for non-adenomatous polyps, LRAs, HRAs and CRC were 5.2%, 15.9%, 22.5% and 2.5%, respectively. The PPVs of positive HRFQ results for non-adenomatous polyps, LRA, HRA and CRC were 4.1%, 10.2%, 14.3% and 1.4%, respectively. The PPVs associated with combined positive FIT and HRFQ results for non-adenomatous polyps, LRAs, HRAs and CRC were 4.5%, 16.4%, 23.7% and 2.8%, respectively.ConclusionOur results suggest that this two-step CRC screening strategy, involving a combination of FIT and HRFQ followed by colonoscopy, is useful to identify early-stage CRC. The high detection rates and PPVs for CRC and adenomas encourage this strategy’s use in ongoing screening programs.

A combination of clinical risk stratification and fecal immunochemical test results to prioritize colonoscopy screening in asymptomatic participants

<h3>Context:</h3> Colorectal cancer (CRC) is the second most common cause of cancer death worldwide. Fecal immunochemical tests (FITs) are currently the most used strategy for population-based CRC screening in Europe and some Asian countries. Positive FIT results should be followed by colonoscopy. <h3>Objective:</h3> To identify the factors associated with false positive FIT results. <h3>Study Design and Analysis:</h3> Each participant completed five different FITs from a single stool sample prior to their colonoscopy. Colonoscopy and associated pathology reports were reviewed. Based on the pathology results, we dichotomized patients as having advanced colorectal neoplasia (ACN) or not. ACN was defined as adenomatous ≥ 10mm or sessile serrated polyps ≥ 10mm; any polyps with villous or tubulovillous pathology, or traditional serrated adenomas; any lesion with high grade dysplasia, or any stage of adenocarcinoma. FITs were false positive if no ACN was found on pathology reports. We used PROC GLIMMIX models in SAS to assess variables associated with false positive FIT results. <h3>Setting:</h3> Three academic medical centers in Iowa, North Carolina, and Texas. <h3>Population Studied:</h3> Participants ages 50-85 years undergoing a screening or surveillance colonoscopy. Participants who did not meet the definition for ACN were included in the current analysis. <h3>Instruments:</h3> Participant self-reported health questionnaire and colonoscopy/pathology review form. <h3>Results:</h3> Of the 3,759 participants, 3,440 did not have ACN and were included in this analysis. The mean age was 62.1 (±7.8) years; 64% were women, 86% White, and 29% Hispanic. The multivariable model showed the odds ratio of having a false positive FIT result vs. a true negative FIT result was 1.02 (95% CI, 1.01-1.03) for every year increase in age, 1.04 (95% CI, 1.03-1.06) for every one unit increase in BMI, 1.82 (95% CI, 1.29-2.56) for current smoker vs. never smoker, 1.33 (95% CI, 1.10-1.60) for regular aspirin use, and 2.12 (95% CI, 1.45-3.10) for blood thinner use, after controlling for the five FITs and other variables in the model. <h3>Conclusion:</h3> Several risk factors were associated with an increased odds for false positive FIT results. These findings were similar to other studies. Clinicians should be aware of these factors which may lead to false positive FITs in FIT-based colorectal cancer screening programs. <h3>Funding:</h3> NIH Grant R01CA215034

BackgroundThe Faecal Immunochemical Test (FIT) is a cornerstone in both colorectal cancer (CRC) screening programs and referral pathways for symptomatic patients. The test identifies haemoglobin in stool and, when present, is used as a referral indicator on the suspected CRC pathway. Since its introduction, the number of referrals with a positive FIT has risen, stretching diagnostic capabilities to the limit. This study examines whether the value of the result is significant and, if so, can be used as part of the triage process.MethodsThis retrospective cohort study analysed patients who underwent FIT as part of a CRC screening program between June 2020 and November 2021 in Wrightington, Wigan and Leigh NHS Foundation Trust. A total of 293 patients contributed clinical data, including FIT scores, presenting symptoms, and diagnostic outcomes. The patients were stratified according to ranges of FIT scores (<10, 11-50, 51-100, 101-150, 151-200, >400). Their correlating outcomes, including the presence of cancer, benign findings (e.g., polyps and diverticular disease), and inflammatory conditions (e.g., colitis), were recorded.ResultsOut of the 293 patients included in the study, 223 were FIT-positive and 70 FIT-negative, with 20 refusing investigations in the FIT-negative group and six in the FIT-positive group.Among the investigated patients, 25 were diagnosed with CRC; all cases were in the FIT-positive group, and none were found in the FIT-negative group. The sensitivity of FIT for CRC detection was 100% (95% CI: 86.7-100%), and the negative predictive value (NPV) was 100% (95% CI: 94.8-100%), confirming FIT's strength as a rule-out test in this cohort. The positive predictive value (PPV) of a positive FIT result for CRC was 11.2% (95% CI: 7.4-15.9%).Of the 25 cancers, 13 (52%) had a FIT value of >400, and five (20%) had a FIT value of 11-50. In this cohort, 76% of CRC were in the sigmoid or rectum, with 63% of these cases associated with FIT values >400 and 15% falling within the lower FIT range of 11-50.For the remaining FIT-positive patients without cancer, 123/198 (62.1%) had a FIT value of 11-50. Of these, 63 (51.2%) had either a polyp, diverticular disease, or colitis. Of the remaining cancer-negative patients, 30/198 (15.2%) had a FIT value of >400, of which 22 (73%) had benign pathology. When symptoms were analysed, most patients had a change in bowel habit, with rectal bleeding being the most typical symptom in the cancer group.ConclusionsFIT is used widely to aid referral for investigating symptoms suggestive of bowel cancer. As more patients are being referred with positive FIT, there is a need to try to rationalise investigations. The premise of this study was to determine whether a low FIT value corresponded with a low chance of finding a cancer in symptomatic patients, thus aiding the triage process, reducing the numbers having unnecessary investigations, and relieving the burden on endoscopy units.In this particular study, none of the FIT-negative patients had bowel cancer, confirming FIT's strong rule-out performance. However, as 20% of cancers occurred among patients with low-positive FIT results (11-50 µg/g), clinicians should remain cautious in interpreting low values as entirely reassuring. While most cancers were seen with FIT >400, PPV remained low overall (~11%), and high FIT scores did not always indicate malignancy.

P-211 Risk of diabetes in subjects with positive fecal immunochemical test: A nationwide population-based study

PurposeA substantial proportion of patients with colorectal cancer (CRC) present with iron deficiency anemia (IDA), and fecal immunochemical test (FIT) has proven to be an effective method for detecting the majority of CRC cases. A combination strategy of FIT results and IDA may be useful for risk stratification for detecting advanced colorectal neoplasia (ACRN). We compared the prevalence of ACRN among four groups stratified by FIT results and the presence of IDA.Materials and MethodsA cross-sectional study was performed on asymptomatic male participants who underwent both FIT and colonoscopy between 2010 and 2014 as part of a comprehensive health screening program in Korea.ResultsOf 17236 participants, 522 (3.0%) showed positive FIT results and 26 (0.2%) had IDA. The mean age of the study participants was 40.8 years. The participants were classified into four groups: positive FIT result/IDA (G1, n=7), positive FIT result/no IDA (G2, n=515), negative FIT result/IDA (G3, n=19), and negative FIT result/no IDA (G4, n=16695). The prevalences of ACRN in G1, G2, G3, and G4 were 28.6, 13.4, 5.3, and 1.5%, respectively (p<0.001) and those of CRC were 28.6, 1.6, 0.0, and 0.01%, respectively (p<0.001). Subjects with positive FIT results and IDA had an increased risk of ACRN and CRC in both group aged <50 and ≥50 years.ConclusionSubjects with positive FIT results and IDA had an increased risk of ACRN. Our results suggest that a combination strategy of FIT and IDA may be helpful in selecting and prioritizing asymptomatic men for colonoscopy.

FITs are superior to gFOBTs in detecting AN and CRC in average-risk individuals. Specificity of both tests was similar in "reference standard: all" studies, whereas specificity was significantly higher for gFOBTs than FITs in "reference standard: positive" studies. However, at pre-specified specificities, the sensitivity of FITs was significantly higher than gFOBTs.