Colon lesions in elderly individuals with positive and negative fecal immunochemical test results among PERSIAN Guilan cohort study (PGCS) population

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.

Purpose: Early-onset colorectal cancer (EOCRC) incidence is rising in a predominantly symptomatic population of young adults. Effective triage tools are needed to identify high-risk individuals in this relatively low incidence population. We examined fecal immunochemical test (FIT) use among adults ages <50 with red flag signs and symptoms for EOCRC and evaluated whether FIT use is predictive of EOCRC risk. Methods: Retrospective cohort study of US Veterans (ages 18-49) receiving Veterans Health Administration (VHA) care during 1999-2022 with a documented EOCRC red flag sign or symptom (abdominal distension, abdominal pain, anemia [non-specific and iron-deficiency], change in bowel habits, constipation, diarrhea, hematochezia, nausea/vomiting) based on International Classification of Diseases, 9th (ICD-9) or 10th (ICD-10) Revision codes, or lab results. The primary exposure was FIT uptake and result, documented via lab results, shown as a three-level variable (no FIT use, negative FIT or positive FIT). The primary outcome was EOCRC diagnosis, derived from linkages to the VA Oncology Domain and National Death Index. Covariates included age at symptom presentation, sex, race and ethnicity, and number of symptoms within 60 days of first symptom presentation. Participants entered the study at first symptom onset and were followed until the first of: incident or fatal EOCRC diagnosis, non-EOCRC-related death, 2 years follow-up, age 50 or December 31, 2022. We derived cumulative CRC incidence estimates using Kaplan-Meier estimation. Multivariable, mixed-effects Cox regression models were used to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI) for CRC risk among those who received a FIT test. Results: Among 751,116 Veterans, 38,019 (5.1%) received a FIT. The most common symptoms yielding a FIT were abdominal pain (29.6%), anemia (20.4%), hematochezia (18.5%), and diarrhea (16.4%). Approximately 76% of patients who received a FIT had one symptom at presentation. Among 38,019 patients who received a FIT, 6,191 (16.3%) had a positive finding. Approximately 1,295 (21%) of 6,191 FIT-positive patients received a diagnostic colonoscopy compared to 46,693 (6.6%) of 713,097 non-FIT patients. After two years of follow-up, patients with a positive FIT had a 1.44% cumulative EOCRC incidence (95% CI: 1.12%-1.77%), compared to a 0.12% among those with a negative FIT (95% CI; 0.08%-0.16%) and 0.12% among those who did not receive a FIT (95% CI: 0.12%-0.13%). The findings correspond to an aHR for EOCRC of 12.81 (95% CI: 8.47-19.36) for FIT-positive patients compared to those with a negative FIT. Conclusions: Among adults ages 18-49 presenting with a red flag sign or symptom to VHA care, FIT use was low. However, a positive FIT result was linked to a substantially elevated EOCRC risk relative to a negative result. To address potential concerns about generalizability, future research should confirm whether systematic use of FIT as a clinical triage tool could help identify symptomatic adults at high EOCRC risk who need a diagnostic colonoscopy. Citation Format: Daniel Sabater Minarim, Kylie Morgan, Lin Liu, Matthew P. Banegas, Maria Elena Martinez, Samir Gupta, Josh Demb. FIT for red flag signs and symptoms of early onset colorectal cancer: low value or viable diagnostic tool? [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: The Rise in Early-Onset Cancers—Knowledge Gaps and Research Opportunities; 2025 Dec 10-13; Montreal, QC, Canada. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(23_Suppl):Abstract nr PR014.

BACKGROUNDFaecal immunochemical test (FIT) has been recommended to assess symptomatic patients for colorectal cancer (CRC) detection. Nevertheless, some conditions could theoretically favour blood originating in proximal areas of the gastrointestinal tract passing through the colon unmetabolized. A positive FIT result could be related to other gastrointestinal cancers (GIC).AIMTo assess the risk of GIC detection and related death in FIT-positive symptomatic patients (threshold 10 μg Hb/g faeces) without CRC.METHODSPost hoc cohort analysis performed within two prospective diagnostic test studies evaluating the diagnostic accuracy of different FIT analytical systems for CRC and significant colonic lesion detection. Ambulatory patients with gastrointestinal symptoms referred consecutively for colonoscopy from primary and secondary healthcare, underwent a quantitative FIT before undergoing a complete colonoscopy. Patients without CRC were divided into two groups (positive and negative FIT) using the threshold of 10 μg Hb/g of faeces and data from follow-up were retrieved from electronic medical records of the public hospitals involved in the research. We determined the cumulative risk of GIC, CRC and upper GIC. Hazard rate (HR) was calculated adjusted by age, sex and presence of significant colonic lesion.RESULTSWe included 2709 patients without CRC and a complete baseline colonoscopy, 730 (26.9%) with FIT ≥ 10 µgr Hb/gr. During a mean time of 45.5 ± 20.0 mo, a GIC was detected in 57 (2.1%) patients: An upper GIC in 35 (1.3%) and a CRC in 14 (0.5%). Thirty-six patients (1.3%) died due to GIC: 22 (0.8%) due to an upper GIC and 9 (0.3%) due to CRC. FIT-positive subjects showed a higher CRC risk (HR 3.8, 95%CI: 1.2-11.9) with no differences in GIC (HR 1.5, 95%CI: 0.8-2.7) or upper GIC risk (HR 1.0, 95%CI: 0.5-2.2). Patients with a positive FIT had only an increased risk of CRC-related death (HR 10.8, 95%CI: 2.1-57.1) and GIC-related death (HR 2.2, 95%CI: 1.1-4.3), with no differences in upper GIC-related death (HR 1.4, 95%CI: 0.6-3.3). An upper GIC was detected in 22 (0.8%) patients during the first year. Two variables were independently associated: anaemia (OR 5.6, 95%CI: 2.2-13.9) and age ≥ 70 years (OR 2.7, 95%CI: 1.1-7.0).CONCLUSIONSymptomatic patients without CRC have a moderate risk increase in upper GIC, regardless of the FIT result. Patients with a positive FIT have an increased risk of post-colonoscopy CRC.

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

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.

Introduction: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths in the United States. For those unable or unwilling to undergo invasive screening, fecal immunochemical test (FIT) is a yearly alternative due to its cost and accessibility compared to the Cologuard. Few studies have examined how patient factors influence FIT outcomes. This study aims to determine whether FIT should be interpreted within the context of patient demographics and medical history. Methods: A retrospective review of patients >50 years old who had a FIT followed by a colonoscopy within 1 year from 2016-2019 was performed. Patients were analyzed based on age, race, body mass index (BMI), comorbidities, smoking, and alcohol use. FIT values above 100 ng/mL were positive based on manufacturer recommendations (Polymedco, NY). Chi-square test was used to compare positive FIT rates within each of the patient demographics and medical history. Fisher’s exact test was used when sparse cells were encountered in contingency tables. False positive (FP) and negative (FN) FIT results were determined by comparing with the gold standard of colonoscopy. Results: 1025 patients were reviewed. 21.8% of FIT results were positive. Factors which differed in positive FIT rates were age (P = 0.003), smoking (P < 0.001), alcohol (P = 0.001), and hypertension (P < 0.001). A significant trend was noted with increasing positive findings with older age (Cochran-Armitage test, P = 0.001). The difference in rates of FP and FN FIT outcomes among each variable underwent further sub-analysis. The FP rate was 66.8% and the FN rate was 12.8%. Higher FN outcomes were noted in those above the age of 70, males and smokers, though the result was only statistically significant for males (P = 0.009). Females were observed to have higher FP rates than males (P = 0.019). African Americans had the highest rates of a positive FIT overall, and the FN rates were the lowest; neither result was statistically significant. Patients on aspirin and with a history of alcohol use had higher FP rates but did not meet statistical significance. Conclusion: Females were found to have higher FP FIT rates compared to males indicating that patient demographics may influence the FIT outcome. We can use this information to identify populations at higher risk of FP or FN FIT outcomes to target CRC screening. Additionally, recalculating the FP and FN rates for each variable by adjusting FIT cutoff may help determine new FIT targets to better improve sensitivity and specificity.Table 1.: Patient characteristics and fecal immunochemical test (FIT) positive rates.

Background:There is convincing evidence from epidemiological studies that meat consumption increases colorectal cancer (CRC) risk. However, assessment of any association with a positive fecal immunochemical test (FIT) in CRC screening has been limited. If a link could be shown this might be helpful for establishing a risk group for colonoscopy.Objective:This study aimed to assess any association between meat consumption and other lifestyle factors and a positive FIT result in a Thai population.Methods:A cross-sectional analytical study was conducted with 1,167 participants in a population-based randomized controlled trial. CRC was screened from May 2016 - February 2017. Subjects aged 45-74 years who met the eligibility criteria were randomly allocated to the study arm. A positive FIT was determined with cut-off 100 ng/mL. Multiple logistic regression was used to analyze any relationship between lifestyle factors and a positive FIT.Result:The total number of subjects was 1,060 (90.8% return rate of FIT). With FIT100, FIT150, and FIT200, positive tests were found in 92 (8.68%), 74 (6.98%), and 60 (5.66%), respectively. No significant associations were noted with any of the variables, except for being aged 60-74 years (ORadj = 1.62, 95%CI: 1.03-2.54) Borderline significance was observed for high consumption of vegetables (ORadj = 0.62, 95%CI: 0.36-1.07) and being male (ORadj = 1.39, 95%CI:0.87-2.22).Conclusion:Despite the evidence from the literature, no association was here found between a positive FIT result and meat consumption or other well-established lifestyle parameters. Being aged 60-74 years was a risk factor which should be taken into account in CRC screening strategy in countries like Thailand with limited access to endoscopy.

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.

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.

Aim: The faecal immunochemical test (FIT) is now widely used in English primary care to triage people who exhibit signs or symptoms of colorectal cancer (CRC). National guidelines for FIT implementation were based on data that acknowledged limitations. This study examines FIT accuracy in primary care patients with low‐ and high‐risk symptoms of CRC.Methods: This study describes a retrospective cohort study in South Yorkshire, UK (n = 2029). Consecutive symptomatic adult patients in primary care undergoing a FIT between 01/04/2021 and 30/04/2021 were assessed. A threshold &gt; 10 μg Hb/g was defined as a positive FIT result. Lower gastrointestinal tract (LGI) investigations were the reference standard. Follow‐up over 24 months was used to identify serious colorectal diseases (CRC, high‐risk polyps and inflammatory bowel disease [IBD]).Results: Five hundred and fifteen (25.4%) patients had a positive FIT. The CRC prevalence was 1.2% (24/2029). Nineteen (79.1%) of the 24 CRC cases had NG12 symptoms, with two (8.3%) having a negative FIT. For CRC detection, FIT showed 91.7% sensitivity (95% CI: 71.5%–98.5%), 75.4% specificity (95% CI: 73.4%–77.2%), 4.3% positive predictive value (PPV) (95% CI: 2.8%–6.5%) and 99.9% negative predictive value (NPV) (95% CI: 99.5%–99.97%). Combining CRC, high‐risk polyps and IBD increased PPV and specificity but decreased sensitivity and NPV.Conclusions: In primary care, FIT safely triages patients having at‐risk CRC risk symptoms. Negative FIT results indicate a low likelihood of CRC and supports safety‐netting interventions.

To improve the interpretation of fecal immunochemical test (FIT) results in colorectal cancer (CRC) cases from screening and referral cohorts. In this comparative observational study, two prospective cohorts of CRC cases were compared. The first cohort was obtained from 10 322 average risk subjects invited for CRC screening with FIT, of which, only subjects with a positive FIT were referred for colonoscopy. The second cohort was obtained from 3637 subjects scheduled for elective colonoscopy with a positive FIT result. The same FIT and positivity threshold (OC sensor; ≥ 50 ng/mL) was used in both cohorts. Colonoscopy was performed in all referral subjects and in FIT positive screening subjects. All CRC cases were selected from both cohorts. Outcome measurements were mean FIT results and FIT scores per tissue tumor stage (T stage). One hundred and eighteen patients with CRC were included in the present study: 28 cases obtained from the screening cohort (64% male; mean age 65 years, SD 6.5) and 90 cases obtained from the referral cohort (58% male; mean age 69 years, SD 9.8). The mean FIT results found were higher in the referral cohort (829 ± 302 ng/mL vs 613 ± 368 ng/mL, P = 0.02). Tissue tumor stage (T stage) distribution was different between both populations [screening population: 13 (46%) T1, eight (29%) T2, six (21%) T3, one (4%) T4 carcinoma; referral population: 12 (13%) T1, 22 (24%) T2, 52 (58%) T3, four (4%) T4 carcinoma], and higher T stage was significantly associated with higher FIT results (P < 0.001). Per tumor stage, no significant difference in mean FIT results was observed (screening vs referral: T1 498 ± 382 ng/mL vs 725 ± 374 ng/mL, P = 0.22; T2 787 ± 303 ng/mL vs 794 ± 341 ng/mL, P = 0.79; T3 563 ± 368 ng/mL vs 870 ± 258 ng/mL, P = 0.13; T4 not available). After correction for T stage in logistic regression analysis, no significant differences in mean FIT results were observed between both types of cohorts (P = 0.10). Differences in T stage distribution largely explain differences in FIT results between screening and referral cohorts. Therefore, FIT results should be reported according to T stage.

Depending on the colorectal cancer (CRC) screening programme, a colonoscopy should be performed within 1-3 months after a positive faecal immunochemical test (FIT) result. However, such short timescales may be difficult to meet and seem trivial when most CRCs take years to develop. To assess the impact of time to colonoscopy on CRC outcomes. This French nationwide retrospective cohort study included individuals with a positive FIT result between 2016 and 2019 and a subsequent colonoscopy performed within 24 months. The risks of CRC, advanced-stage CRC and advanced adenoma (AA) according to time interval to colonoscopy were assessed and evaluated on individual and socio-geographic characteristics. Overall, 374 113 FIT-positive individuals underwent post-FIT colonoscopy (86.6% compliance rate), with 21 616 CRCs and 122 359 AAs diagnosed. Compared with the 2-3 months interval class, no increased risk of CRC, advanced-stage CRC or AA was observed after 3 months up to 24 months, with adjusted odds ratio after 12 months at 0.93 (0.95 CI 0.83 to 1.03), 1.04 (0.85 to 1.25) and 0.88 (0.82 to 0.93), respectively. Individuals with high faecal haemoglobin concentrations (f-Hb ≥200 µg/g) were respectively eight, eleven and two times more likely to have a CRC, an advanced-stage CRC or an AA as compared with the 30-40 µg/g class. No increased risk of CRC, advanced-stage CRC or AA was observed up to 24 months. Our findings suggest that ensuring colonoscopy compliance after a positive FIT may take precedence over rigid adherence to interval. The higher the f-Hb, the sooner the colonoscopy should be performed.

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

Fecal immunochemical test (FIT)-based screening has been recommended as an option for population colorectal cancer (CRC) screening. However, the studies on factors associated with false-positive FIT results are still limited. To identify the clinical and endoscopic factors associated with false-positive results of FIT for advanced neoplasia (AN) and to evaluate whether false-positive FIT results would be indicative of other digestive tract diseases. We prospectively enrolled 929 participants aged 50 years or older at Qilu Hospital of Shandong University between April 2020 and April 2021. The two-sample FIT was used in this study and ≥ 10 μg/g in either of two stool samples was regarded as the positive FIT result. All these participants underwent subsequent gastroscopy and colonoscopy. False positive FIT results were defined as positive FITs without AN detected in colonoscopies. With a cut-off value of 10 µg/g, the positive rate of FIT was 16.0%. For detecting AN, the sensitivity and specificity were 64.6% and 87.6%, respectively. After adjusting confounding factors, male (OR = 1.61; 95% CI, 1.05–2.48; P = 0.030), colorectal inflammation (OR = 2.99; 95% CI, 1.38–6.04; P = 0.003), presence of three or more non-advanced adenomas (OR = 1.78; 95% CI, 1.11–2.82; P = 0.015) and gastric cancer (OR = 11.33; 95% CI, 2.40–59.52; P = 0.002) were associated with higher risk of false-positive FIT results. Although the FIT results may be false-positive for detecting AN, they may still suggest medical issues that warrant closer medical follow-up and intervention. Meanwhile, routine upper endoscopy investigation for false positive patients was not recommended. Upper endoscopy may be considered conditionally in FIT-positive/AN-negative patients with additional risk factors. Large-scale research is required to clarify this issue. (ClinicalTrials.gov ID: NCT04454099) Trial identification number: ClinicalTrials.gov ID: NCT04454099 (URL: https://clinicaltrials.gov/ct2/show/NCT04454099) registered on July 1, 2020.