Changes in faecal haemoglobin values over sequential rounds of faecal immunochemical tests (FIT) in a surveillance population

In the UK, patients with one or two adenomas, of which at least one is ≥ 10 mm in size, or three or four small adenomas, are deemed to be at intermediate risk of colorectal cancer (CRC) and referred for surveillance colonoscopy 3 years post polypectomy. However, colonoscopy is costly, can cause discomfort and carries a small risk of complications. To determine whether or not annual faecal immunochemical tests (FITs) are effective, acceptable and cost saving compared with colonoscopy surveillance for detecting CRC and advanced adenomas (AAs). Diagnostic accuracy study with health psychology assessment and economic evaluation. Participants were recruited from 30 January 2012 to 30 December 2013 within the Bowel Cancer Screening Programme in England. Men and women, aged 60-72 years, deemed to be at intermediate risk of CRC following adenoma removal after a positive guaiac faecal occult blood test were invited to participate. Invitees who consented and returned an analysable FIT were included. We offered participants quantitative FITs at 1, 2 and 3 years post polypectomy. Participants testing positive with any FIT were referred for colonoscopy and not offered further FITs. Participants testing negative were offered colonoscopy at 3 years post polypectomy. Acceptibility of FIT was assessed using discussion groups, questionnaires and interviews. The primary outcome was 3-year sensitivity of an annual FIT versus colonoscopy at 3 years for detecting advanced colorectal neoplasia (ACN) (CRC and/or AA). Secondary outcomes included participants' surveillance preferences, and the incremental costs and cost-effectiveness of FIT versus colonoscopy surveillance. Of 8008 invitees, 5946 (74.3%) consented and returned a round 1 FIT. FIT uptake in rounds 2 and 3 was 97.2% and 96.9%, respectively. With a threshold of 40 µg of haemoglobin (Hb)/g faeces (hereafter referred to as µg/g), positivity was 5.8% in round 1, declining to 4.1% in round 3. Over three rounds, 69.2% (18/26) of participants with CRC, 34.3% (152/443) with AAs and 35.6% (165/463) with ACN tested positive at 40 µg/g. Sensitivity for CRC and AAs increased, whereas specificity decreased, with lower thresholds and multiple rounds. At 40 µg/g, sensitivity and specificity of the first FIT for CRC were 30.8% and 93.9%, respectively. The programme sensitivity and specificity of three rounds at 10 µg/g were 84.6% and 70.8%, respectively. Participants' preferred surveillance strategy was 3-yearly colonoscopy plus annual FITs (57.9%), followed by annual FITs with colonoscopy in positive cases (31.5%). FIT with colonoscopy in positive cases was cheaper than 3-yearly colonoscopy (£2,633,382), varying from £485,236 (40 µg/g) to £956,602 (10 µg/g). Over 3 years, FIT surveillance could miss 291 AAs and eight CRCs using a threshold of 40 µg/g, or 189 AAs and four CRCs using a threshold of 10 µg/g. Annual low-threshold FIT with colonoscopy in positive cases achieved high sensitivity for CRC and would be cost saving compared with 3-yearly colonoscopy. However, at higher thresholds, this strategy could miss 15-30% of CRCs and 40-70% of AAs. Most participants preferred annual FITs plus 3-yearly colonoscopy. Further research is needed to define a clear role for FITs in surveillance. Evaluate the impact of ACN missed by FITs on quality-adjusted life-years. Current Controlled Trials ISRCTN18040196. National Institute for Health Research (NIHR) Health Technology Assessment programme, NIHR Imperial Biomedical Research Centre and the Bobby Moore Fund for Cancer Research UK. MAST Group Ltd provided FIT kits.

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.

Despite widespread use of fecal immunochemical tests (FITs) for colorectal cancer (CRC) screening, data to guide test selection are limited. To compare the performance characteristics of 5 commonly used FITs, using colonoscopy as the reference standard. Cross-sectional study. (ClinicalTrials.gov: NCT03264898). Three U.S. academic medical centers and affiliated endoscopy units. Patients aged 50 to 85 years undergoing screening or surveillance colonoscopy. Participants completed 5 different FITs before their colonoscopy, including 4 qualitative tests (Hemoccult ICT, Hemosure iFOB, OC-Light S FIT, QuickVue iFOB) and 1 quantitative test (OC-Auto FIT, which was run at the manufacturer's threshold for positivity of >100 ng/mL). The primary outcome was test performance (sensitivity and specificity) for each of the 5 FITs for advanced colorectal neoplasia (ACN), defined as advanced polyps or CRC. Positivity rates, positive and negative predictive values, and rates of unevaluable tests were compared. Multivariable models were used to identify factors affecting sensitivity. A total of 3761 participants were enrolled, with a mean age of 62.1 years (SD, 7.8); 63.2% of participants were female, 5.7% were Black, 86.4% were White, and 28.7% were Hispanic. There were 320 participants with ACN (8.5%), including 9 with CRC (0.2%). The test positivity rate varied 4-fold (3.9% to 16.4%) across FITs. Rates of unevaluable FITs ranged from 0.2% to 2.5%. The sensitivity for ACN varied from 10.1% to 36.7%, and specificity varied from 85.5% to 96.6%. Differences in sensitivity between FITs were all statistically significantly different except between Hemosure iFOB and QuickVue iFOB, and specificity differences were all statistically significantly different from one another. In addition to FIT brand, distal location of ACN was also associated with higher FIT sensitivity. The study did not assess the programmatic sensitivity of annual FIT. Although considered a single class, FITs have varying test performance for detecting ACN and should not be considered interchangeable. National Institutes of Health.

Quantitation of Hemoglobin Improves Fecal Immunochemical Tests for Noninvasive Screening

Comparing Fecal Immunochemical Tests: Improved Standardization Is Needed

ObjectiveThe English Bowel Cancer Screening Programme (BCSP) recommends 3 yearly colonoscopy surveillance for patients at intermediate risk of colorectal cancer (CRC) postpolypectomy (those with three to four small adenomas or...

Colon Cancer Screening Models: Lessons and Challenges

Objective To investigate whether screening kidney transplant recipients aged over 50 years for colorectal cancer with a faecal immunochemical test for haemoglobin might be justified, by determining the prevalence of...

Introduction Individuals at intermediate-risk for colorectal cancer (CRC) following adenoma removal within the English Bowel Cancer Screening Programme (BCSP) are invited for three-yearly surveillance colonoscopy. Given the invasive nature of colonoscopy and scarcity of endoscopy resources, there is a need for an alternative surveillance method. We aimed to determine whether annual testing with the faecal immunochemical test (FIT) is an effective alternative. Methods Individuals aged 60–72 years and scheduled for surveillance following removal of intermediate-risk adenomas were recruited within the BCSP from January 2012 to December 2013. Quantitative FIT (OC-Sensor, Eiken) was offered at one, two, and three years post-polypectomy. Invitees who returned a completed consent form and an analysable FIT at Round 1 were included. Participants testing positive (≥40 µg haemoglobin (Hb)/g faeces) at Rounds 1 or 2 were offered early colonoscopy and were not invited to further FIT rounds. All other participants were offered the routine three-year surveillance colonoscopy. Diagnostic accuracy for CRC and advanced adenomas (AAs: adenomas≥10 mm, with tubulovillous or villous histology, or high grade dysplasia) was calculated at each round, using colonoscopy as the reference standard. We estimated diagnostic accuracy with lower haemoglobin thresholds and multiple rounds. Results Of 8008 invitees, 5946 (74%) consented and returned an analysable FIT at Round 1. Uptake of FIT was higher (97%) in Rounds 2 and 3. FIT positivity decreased by round, from 6% to 4% in Rounds 1 to 3. In total, 26 participants were diagnosed with CRC and 443 with AAs. At 40 µg/g, sensitivity and specificity of the first FIT were, respectively, 31% and 94% for CRC and 18% and 95% for AAs. Sensitivities for CRC and AAs were higher, and specificities lower, with lower thresholds and multiple rounds. At 10 µg/g, the programme sensitivity and specificity of three rounds were, respectively, 85% and 71% for CRC and 57% and 73% for AAs. Conclusions Annual low threshold FIT achieved relatively high sensitivity for CRC over three years. If this strategy replaced three-yearly surveillance colonoscopy, the number of colonoscopies could potentially be reduced by 70%. However, sensitivity for AAs was limited. Further research is needed to consider the implications for clinical practice of missing CRCs and AAs with FIT-based surveillance.

Age, male sex, smoking and metabolic syndrome as risk factors of advanced colorectal neoplasia for fecal immunochemical test negative patients

Screening and Surveillance Colonoscopy and COVID-19: Avoiding More Casualties

<h3>Context:</h3> Colorectal cancer (CRC) is the second leading cause of cancer death worldwide; it is largely preventable with appropriate screening. Fecal immunochemical tests (FIT) followed by colonoscopy, if positive, is a cost-effective option for CRC screening. There are limited data on the performance of various FITs for detecting advanced colorectal neoplasia (ACN). <h3>Objective:</h3> To compare the performance of five commonly used FITs for detecting ACN, using colonoscopy as the gold standard. <h3>Methods:</h3> Patients aged 50-85 years undergoing screening or surveillance colonoscopy were recruited from three academic medical centers in the United States. Each patient completed five FITs on a single stool sample prior to colonoscopy. FITs were analyzed according to manufacturer instructions and the subsequent colonoscopy and pathology reports were abstracted. ACN was defined as any advanced pre-cancerous lesion (adenomatous or sessile serrated polyps 10 mm or greater); villous, tubulovillous, or traditional serrated adenoma of any size, any lesion with high-grade dysplasia, or any stage adenocarcinoma. Based on histology, we calculated the test characteristics for each FIT for ACN. We used PROC GLIMMIX models in SAS to compare sensitivity and specificity across the different brands, accounting for within-patient correlation. <h3>Results:</h3> For the 3759 participants enrolled, the mean (SD) age was 62 (7.8) years, 63% were women, 86% white, and 29% Hispanic. Based on colonoscopy, 319 patients (8.5%) had ACN, including 9 participants (0.2%) with CRC and 310 (8.2%) with advanced adenomas. The positivity rates for each test were 4%, 13%, 16%, 11%, and 6%. The sensitivity for detecting ACN was 10%, 27%, 37%, 30%, and 19%; and the corresponding specificities were 97%, 89%, 85%, 91%, and 96%. Positive predictive values were 21%, 18%, 20%, 23%, and 29%; and the corresponding negative predictive values were 92%, 93%, 93%, 93%, and 93%. We found statistically significant differences in sensitivity (p&lt;.0001) and specificity (p&lt;.0001) across FITs. <h3>Conclusion:</h3> There were substantial variations in test performance among different FITs when used for single-sample stool testing. The ideal test for population-based screening should have a high sensitivity without a substantial loss of specificity and depends on resources for colonoscopy. These differences could impact regulatory policy and FIT selection by healthcare providers. <h3>Funding:</h3> NIH R01 CA215034

<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

The Cost-effectiveness of Adopting Risk-scoring Systems for Population-Based Colorectal Cancer Screening

Enhancing fecal immunochemical test (FIT)-based colorectal cancer (CRC) screening requires identifying additional predictive factors for colorectal neoplasia beyond current-round FIT concentration. We investigated whether first-round FIT concentration could predict colorectal neoplasia detection in the second screening round, using data from the randomized controlled trial Screening of Swedish Colons (SCREESCO). We conducted a cross-sectional analysis of SCREESCO FIT-arm participants with negative two-stool FIT (<10 μg Hb/g feces) in the first screening round, followed by a positive FIT (≥10 μg Hb/g feces) in the second round two years later with work-up colonoscopy. We used binary regression models to assess risk factors for colorectal neoplasia, including CRC and advanced colorectal neoplasia (ACN), at colonoscopy, according to participants' characteristics and first- and second-round FIT concentrations. In total, 1,991 individuals were included, with median FIT concentrations of 2.2 and 21.8 μg Hb/g feces in the first and second rounds, respectively. Higher first-round FIT concentration was associated with increased risks of CRC and ACN in the second round. Compared to those with first-round FIT concentrations of 0.0-1.9 μg Hb/g feces, the risk ratios for ACN were 1.38 (95% CI: 1.07-1.80) for 2.0-5.9 and 1.85 (95% CI: 1.38-2.48) for 6.0-9.9 μg Hb/g feces. For fixed second-round FIT concentration, the absolute risk of ACN increased in accordance with higher first-round FIT concentration. Even an increase in low levels of FIT concentration is associated with future CRC and ACN detection. Combining first- and second-round FIT results could enhance the efficacy of screening. ClinicalTrials.gov number, NCT02078804.