BackgroundThis study has attempted to assess the effectiveness of quantitative faecal immunochemical tests (FIT) for triage of people presenting with lower abdominal symptoms, where a referral to secondary care for investigation of suspected colorectal cancer (CRC) is being considered, particularly when the 2-week criteria are not met.MethodsWe conducted a systematic review following published guidelines for systematic reviews of diagnostic tests. Twenty-one resources were searched up until March 2016. Summary estimates were calculated using a bivariate model or a random-effects logistic regression model.ResultsNine studies are included in this review. One additional study, included in our systematic review, was provided as ‘academic in confidence’ and cannot be described herein.When FIT was based on a single faecal sample and a cut-off of 10 μg Hb/g faeces, sensitivity estimates indicated that a negative result using either the OC-Sensor or HM-JACKarc may be adequate to rule out nearly all CRC; the summary estimate of sensitivity for the OC-Sensor was 92.1% (95% confidence interval, CI 86.9–95.3%), based on four studies (n = 4091 participants, 176 with CRC), and the only study of HM-JACKarc to assess the 10 μg Hb/g faeces cut-off (n = 507 participants, 11 with CRC) reported a sensitivity of 100% (95% CI 71.5–100%). The corresponding specificity estimates were 85.8% (95% CI 78.3–91.0%) and 76.6% (95% CI 72.6–80.3%), respectively.When the diagnostic criterion was changed to include lower grades of neoplasia, i.e. the target condition included higher risk adenoma (HRA) as well as CRC, the rule-out performance of both FIT assays was reduced.ConclusionsThere is evidence to suggest that triage using FIT at a cut-off around 10 μg Hb/g faeces has the potential to correctly rule out CRC and avoid colonoscopy in 75–80% of symptomatic patients.Systematic review registrationPROSPERO 42016037723Electronic supplementary materialThe online version of this article (doi:10.1186/s12916-017-0944-z) contains supplementary material, which is available to authorized users.

Several randomized controlled trials have shown that population-based screening using faecal occult blood testing (FOBT) can reduce mortality from colorectal neoplasia. Based on this evidence, a number of countries have introduced screening for colorectal cancer (CRC) and high-risk adenoma and many others are considering its introduction. The aim of this article is to critically review the current status of faecal markers as population-based screening tests for these neoplasia. Most of the available faecal tests involve the measurement of either occult blood or a panel of DNA markers. Occult blood may be measured using either the guaiac faecal occult blood test (gFOBT) or a faecal immunochemical test (iFOBT). Although iFOBT may require a greater initial investment, they have several advantages over gFOBT, including greater analytical sensitivity and specificity. Their use results in improved clinical performance and higher uptake rates. Importantly for population screening, some of the iFOBTs can be automated and provide an adjustable cutoff for faecal haemoglobin concentration. However, samples for iFOBT, may be less stable after collection than for gFOBT. For new centres undertaking FOBT for colorectal neoplasia, the European Group on Tumour Markers recommends use of a quantitative iFOBT with an adjustable cutoff point and high throughput analysis. All participants with positive FOBT results should be offered colonoscopy. The panel recommends further research into increasing the stability of iFOBT and the development of improved and affordable DNA and proteomic-based tests, which reduce current false negative rates, simplify sample transport and enable automated analysis.Colorectal cancer (CRC) is the third most prevalent cancer worldwide, with an estimated one million new cases and a half million deaths each year. 1,2 After lung cancer, CRC is the second most common cause of death from cancer for men and women combined.Although many screening tests are available for CRC and advanced adenoma, the most widely used is faecal occult blood testing (FOBT). The use of FOBT has been shown to reduce cancer mortality in four large randomized trials. [3][4][5][6][7] Several expert groups therefore now recommend that all average-risk men and women should undergo screening for CRC and advanced adenoma (Table 1). In light of these recommendations, population screening for these lesions has recently been initiated in several countries.This article critically reviews the current status of faecal markers in screening for CRC and high-risk adenoma (i.e., > 10 mm, 3 more adenomatous polyps of any size, significant villous component, or high grade dysplasia), and makes recommendations for their use in population-based screening. In preparing the article, the literature relevant to faecal screening tests for colorectal neoplasia was reviewed. Particular attention was given to systematic reviews, prospective randomised trials and guidelines published by expert panels.

No abstract

INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics. METHODS: Whole stool samples (n 5 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n 5 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n 5 119), and non-AAs (n 5 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing. RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P 5 0.005), larger lesions (P 5 0.03), and lesions with tubulovillous architecture (P 5 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n 5 19) from individuals with low-risk AAs (n 5 52) was not significantly different.

Background: Adjusting the threshold for positivity of quantitative fecal immunochemical tests (FIT) allows for controlling the number of follow-up colonoscopies in a screening program. However, it is unknown to what extent higher cutoff levels affect detection rates of screen-relevant neoplasia. This study aimed to assess the effect of higher cutoff levels of a quantitative FIT on test positivity rate and detection rate of early-stage colorectal cancers (CRC).Methods: Subjects above 40 years old scheduled for colonoscopy in 5 hospitals were asked to sample a single FIT (OC sensor) before colonoscopy. Screen-relevant neoplasia were defined as advanced adenoma or early-stage cancer (stage I and II). Positivity rate, sensitivity, and specificity were evaluated at increasing cutoff levels of 50 to 200 ng/mL.Results: In 2,145 individuals who underwent total colonoscopy, 79 patients were diagnosed with CRC, 38 of which were with early-stage disease. Advanced adenomas were found in 236 patients. When varying cutoff levels from !50 to !200 ng/mL, positivity rates ranged from 16.5% to 10.2%. With increasing cutoff levels, sensitivity for early-stage CRCs and for screen-relevant neoplasia ranged from 84.2% to 78.9% and 47.1% to 37.2%, respectively.Conclusions: Higher FIT cutoff levels substantially decrease test positivity rates with only limited effects on detection rates of early-stage CRCs. However, spectrum bias resulting in higher estimates of sensitivity than would be expected in a screening population may be present.Impact: Higher cutoff levels can reduce strain on colonoscopy capacity with only a modest decrease in sensitivity for curable cancers. Cancer Epidemiol Biomarkers Prev; 20(2); 272-80. Ó2010 AACR.