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

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

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

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%.

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.

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.

Is this the end of colonoscopy screening for colorectal cancer? An Asia-Pacific perspective.

1University of Dundee, Nethergate, Dundee, DD1 4HN, Scotland, UK *Author for correspondence: r.j.c.steele@dundee.ac.uk The most commonly used strategy in colo­ rectal cancer (CRC) screening pro grams involves the use of stool tests to detect occult blood, and guaiac fecal occult blood tests (gFOBTs) are, to date, the only fecal tests shown to reduce CRC mortality in population­based randomized trials [1]. However, gFOBTs also carry disadvantages. A major concern is that interval cancers account for around 50% of cancers detected in gFOBT screened populations [2] and recent data show that gFOBTs are less sensitive in women than in men, and in both rectal and right­sided cancers when compared with left­sided disease [2,3]. In addition, the test is associated with a high false­positive rate with no neoplasia detected in around half of colonoscopies performed following a positive gFOBT [2,3]. This may be, in part, explained by the fact that gFOBTs are not specific for human hemoglobin (Hb) and are subject to possible dietary interference from, for example, red meat and high­peroxidase fruits and vegetables. As a result, it has been common practice to instruct participants to adhere to dietary restrictions ahead of sample collection, although this may act as a barrier to screening and affect participation rates [4]. However, data from a meta­analysis did not support dietary restrictions with gFOBTs, leading to recommendations that restrictions are abandoned to improve adherence rates [5]. Fecal immunochemical tests (FITs) are now available and are increasingly being used in screening programs. Unlike gFOBTs, FITs are specific for the detection of human Hb, eliminating any potential for dietary interference, and are also more specific than gFOBT for lower gastrointestinal bleeding. In addition, modern FITs generally allow a more convenient method of sample collection, and are associated with better participation rates [6]. Another major advantage of FIT is that automated versions not only eliminate interobserver variability, but also the quantitative nature of these tests allow provision of a measured fecal Hb concentration. Screening program “...the adoption of fecal immunochemical tests in colorectal cancer screening programs has potential to address participation, appropriate positivity rates and the problem of false‐negative results.” EDITORIAL

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.

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.

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.

BackgroundIn the Dutch colorectal cancer (CRC) screening programme, individuals receive a faecal immunochemical test (FIT) to do at home. After a positive FIT result, a follow-up colonoscopy is recommended to identify CRC or advanced adenomas (AA). GPs may influence their patients’ decisions on adherence to follow-up by colonoscopy.AimTo explore GPs’ perspectives on the CRC screening programme and their potential influence on FIT-positive patients to follow up with the recommended colonoscopy.Design & settingSemi-structured interviews among GPs in Amsterdam, the Netherlands.MethodGPs were approached using purposive sampling. Analysis was performed on 11 interviews using open coding and constant comparison.ResultsAll interviewed GPs would recommend FIT-positive patients without obvious contraindications to adhere to a follow-up colonoscopy. If patients were likely to be distressed by a positive FIT result, most GPs described using reassurance strategies emphasising a low cancer probability. Most GPs stressed the probability of false-positive FIT results. Some described taking a positive screening result in CRC screening less seriously than one in breast cancer screening. Most GPs underestimated CRC and AA probabilities after a positive FIT result. When told the actual probabilities, some stated that this knowledge might change the way they would inform patients.ConclusionThese results imply that some of the interviewed GPs have too low a perception of the risk associated with a positive FIT result, which might influence their patients’ decision-making. Simply informing GPs about the actual rates of CRC and AA found in the screening programme might improve this risk perception.

Goals -We aimed to determine the performance of the OC-Auto ® Micro 80 fecal immunochemical test (FIT) in an average-risk population receiving care in an integrated, academic-community health system.Background-The FIT is the most used colorectal cancer (CRC) screening test worldwide. However, many Food and Drug Administration-cleared FIT products have not been evaluated in clinical settings.Study-We performed a retrospective cohort study of patients (50–75 years old) in the University of Washington Medicine healthcare system who were screened for CRC by OC-Auto ® Micro 80 FIT between March 2016 and September 2021. We used electronic health records to extract patient- and clinic-level factors, FIT use, colonoscopy and pathology findings. The primary outcomes were the FIT positivity rate and neoplasms detected at colonoscopy. Secondary outcomes were FIT positivity by sex and safety-net vs. non-safety-net clinical settings.Results-We identified 39,984 FITs completed by 26,384 patients; 2,411 (6.0%) had a positive FIT result (>100 ng/mL of hemoglobin in buffer) and 1,246 (51.7%) completed a follow-up colonoscopy. The FIT positive rate was 7.0% in men and 5.2% in women (p <0.01). Among those who completed a colonoscopy after an abnormal FIT result, the positive predictive value (PPV) for CRC, advanced adenoma, and advanced neoplasia was 3.0%, 20.9%, and 23.9%, respectively.Conclusion-In a retrospective analysis of a large heterogeneous population, the OC-Auto ® Micro 80 FIT for CRC screening demonstrated a positivity rate of 6.0% and a PPV for CRC of 3.0%.

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

Quantitation of Hemoglobin Improves Fecal Immunochemical Tests for Noninvasive Screening

A four year old girl presented with varicella gangrenosa, and haematological investigations showed a disseminated intravascular coagulation. The child subsequently developed a unilateral deep venous thrombosis. She was treated with oral steroids and intravenous heparin and made a full recovery.