Sensitivity Of Faecal Immunochemical Test Research Articles

Noninvasive colorectal cancer screening techniques: literature review

Fecal DNA testing is a noninvasive method recommended by professional medical societies for colorectal cancer screening in individuals with intermediate risk of the disease. Adenamatous and serrated lesions, as well as cancer, lead to exfoliation of cells containing neoplastic altered DNA which, in turn, can be detected with sensitive testing methods aimed at specific genetic and epigenetic biomarkers. Mt-sDNA test approved by the United States Food and Drug Administration in 2014 showed sensitivity of 92 % for detection of colorectal cancer which is much higher than sensitivity of fecal immunochemical test (74 %).

Sensitivity of fecal immunochemical test and risk factors for interval colorectal cancer in a French population

BackgroundColorectal cancer (CRC) screening using fecal immunochemical testing (FIT) aims to detect pre-symptomatic colorectal lesions and reduce CRC mortality. AimsThe objectives of this study were to determine the FIT sensitivity for diagnosis of CRC, the impact of diagnostic circumstances on treatment and survival, and risk factors for interval cancer (IC). MethodsThis population-based study evaluated the 2016–2017 CRC screening campaign in Finistère, France. CRCs were classified according to diagnostic circumstances: screen-detected CRC (SD-CRC), CRC with delayed diagnosis, IC after negative FIT (FIT-IC), post-colonoscopy CRC, CRC in non-responders and CRC in the excluded population. ResultsThis study included 909 CRCs: 248 SD-CRCs (6% of positive FIT) and 60 FIT-ICs (0.07% of negative FIT). The FIT sensitivity for CRC was 80.5% (CI95%: 76.1–84.9) at the threshold of 30 µg hemoglobin/g feces used in France. In multivariate analysis, proximal (OR:6.73) and rectal locations (OR:7.52) were associated with being diagnosed with FIT-IC rather than SD-CRC. The FIT positivity threshold maximizing the sum of sensitivity and specificity was found to be 17 µg/g, with 14 additional CRCs diagnosed compared to the current threshold. ConclusionsOur study confirms the good sensitivity of FIT. A decrease of the FIT detection threshold could optimize sensitivity.

Faecal immunochemical testing in the COVID-19 era: balancing risk and costs

Faecal immunochemical testing in the COVID-19 era: balancing risk and costs

Sensitivity of Fecal Immunochemical Test for Colorectal Cancer Detection Differs According to Stage and Location

Fecal immunochemical tests (FITs) are widely used for colorectal cancer (CRC) screening. FITs detect most CRCs. Although detection of CRC at early stages is most relevant for reducing CRC mortality, there is limited evidence for the stage-specific sensitivity of the FIT in CRC detection. We estimated stage- and location-specific sensitivities of a quantitative FIT in a large cohort of patients with CRC. Fecal samples were collected before treatment from 435 patients with newly diagnosed CRC. Sensitivities of a quantitative FIT (FOB Gold, Sentinel Diagnostics; Milano, Italy) for tumors of different T stages and overall TNM stages (according to Union for International Cancer Control) were calculated at the cutoff recommended by the manufacturer (17 μg/g feces) and at alternative cutoffs, ranging from 10 to 40 μg/g feces, overall and stratified by tumor location. At the cutoff recommended by the manufacturer, the FIT detected T1 tumors with 52% sensitivity (95% CI, 37%-67%), T2 tumors with 79% sensitivity (95% CI, 68%-88%), T3 tumors with 93% sensitivity (95% CI, 89%-95%), and T4 tumors with 84% sensitivity (95% CI, 72%-92%) (Ptrend < .0001). The FIT detected stage I cancers with 68% sensitivity (95% CI, 57%-78%), stage II cancers with 92% sensitivity (95% CI, 87%-96%), stage III cancers with 82% sensitivity (95% CI, 73%-89%), and stage IV cancers with 89% sensitivity (95% CI, 80%-95%) (Ptrend 0.01). The FIT detected T1 colorectal tumors with sensitivity values that were 22%-52% lower than for tumors of other T stages and stage I CRC with sensitivity values that were 11%-33% lower than for later-stage CRCs, at any of the evaluated cutoff values. The FIT detected T1 and stage I CRCs in the distal colon with sensitivity values of 32% and 52%, respectively. Although the FIT identifies patients with CRC with overall high sensitivity, it can miss approximately one-third of stage I CRCs. Studies are needed to increase noninvasive detection of early-stage CRC.

Stage-Specific Sensitivity of Fecal Immunochemical Tests for Detecting Colorectal Cancer: Systematic Review and Meta-Analysis.

OBJECTIVE:Fecal immunochemical tests (FITs) detect the majority of colorectal cancers (CRCs), but evidence for variation in sensitivity according to the CRC stage is sparse and has not yet been systematically synthesized. Thus, our objective was to systematically review and summarize evidence on the stage-specific sensitivity of FITs.METHODS:We screened PubMed, Web of Science, Embase, and the Cochrane Library from inception to June 14, 2019, for English-language articles reporting on the stage-specific sensitivity of FIT for CRC detection using colonoscopy as a reference standard. Studies reporting stage-specific sensitivities and the specificity of FIT for CRC detection were included. Summary estimates of sensitivity according to the CRC stage and study setting (screening cohorts, symptomatic/diagnostic cohorts, and case-control studies) were derived from bivariate meta-analysis.RESULTS:Forty-four studies (92,447 participants including 3,034 CRC cases) were included. Pooled stage-specific sensitivities were overall very similar but suffered from high levels of imprecision because of small case numbers when calculated separately for screening cohorts, symptomatic/diagnostic cohorts, and case-control studies. Pooled sensitivities (95% confidence intervals) for all studies combined were 73% (65%–79%) for stage-I-CRCs and 80% (74%–84%), 82% (77%–87%), and 79% (70%–86%) for the detection of CRC stages II, III, and IV, respectively. Even substantially larger variation was seen in sensitivity by T-stage, with summary estimates ranging from 40% (21%–64%) for T1 to 83% (68%–91%) for T3-CRC.DISCUSSION:Although FITs detect 4 of 5 CRCs at stages II–IV, the substantially lower sensitivity for stage-I-CRC and, in particular, T1 CRC indicates both need and potential for further improvement in performance for the early detection of CRC.

Overestimated Sensitivity of Fecal Immunochemical Tests in Screening Cohorts With Registry-Based Follow-up.

Several recent studies have reported very high estimates of sensitivity and specificity of fecal immunochemical tests (FITs) at seemingly high levels of precision using registry-based follow-up of participants in very large FIT-based screening programs. We aimed to assess the validity of estimates of diagnostic performance parameters derived by this indirect approach. We modeled expected values of sensitivity and specificity of colorectal cancer detection in studies using the indirect approach and their deviation from true values under a broad range of plausible assumptions, and we compared these expected values with recently reported estimates of FIT sensitivity and specificity from such studies. Using a sensitivity of 75% and specificity of 93.6% (from studies using a direct approach, i.e., colonoscopy follow-up of all participants), the indirect approach would be expected to yield sensitivities between 84.5% and 91.1% and specificities between 93.4% and 93.6% under a range of realistic assumptions regarding colonoscopic follow-up rates of positive FITs and clinical manifestation rates of preclinical colorectal cancer. Very high sensitivities of FITs recently reported with seemingly very high levels of precision by several large-scale registry-based studies, which are in line with expected results based on our model calculations, are likely to be strongly overestimated and need to be interpreted with due caution.

Effect of a Single Aspirin Dose Prior to Fecal Immunochemical Testing on Test Sensitivity for Detecting Advanced Colorectal Neoplasms

Fecal immunochemical tests for hemoglobin are widely used for colorectal cancer (CRC) screening. Observational studies suggested that sensitivity of fecal immunochemical tests for detecting advanced neoplasms could be increased by acetylsalicylic acid (aspirin), especially among men. To evaluate the potential to increase sensitivity of fecal immunochemical tests by administering a single 300-mg oral aspirin dose 2 days before stool sampling. A randomized, placebo-controlled, double-blind trial was conducted in 14 gastroenterology practices and 4 hospitals in Germany, and included 2422 men and women aged 40 to 80 years scheduled for colonoscopy, with no recent use of aspirin or other drugs with antithrombotic effects (enrollment from June 2013 to November 2016, and final follow-up January 27, 2017). Administration of a single tablet containing 300 mg of aspirin (n = 1208) or placebo (n = 1214) 2 days before fecal sampling for fecal immunochemical test. The primary outcome was sensitivity of a quantitative fecal immunochemical test at 2 predefined cutoffs (10.2 and 17-μg Hb/g stool) for detecting advanced neoplasms (colorectal cancer or advanced adenoma). Among 2422 randomized patients (mean [SD] age, 59.6 [7.9] years; 1219, 50%, men), 2134 were included in the analysis (78% for primary screening colonoscopy, 22% for diagnostic colonoscopy). Advanced neoplasms were identified in 224 participants (10.5%), including 8 participants (0.4%) with CRC and 216 participants (10.1%) with advanced adenoma. Sensitivity was 40.2% in the aspirin group and 30.4% in the placebo group (difference 9.8%, 95% CI, -3.1% to 22.2%, P = .14) at cutoff 10.2-μg Hb/g stool and 28.6% in the aspirin and 22.5% in the placebo group (difference 6.0%, 95% CI, -5.7% to 17.5%, P = .32) at cutoff 17-μg Hb/g stool. Among adults aged 40 to 80 years not using aspirin or other antithrombotic medications, administration of a single dose of oral aspirin prior to fecal immunochemical testing, compared with placebo, did not significantly increase test sensitivity for detecting advanced colorectal neoplasms at 2 predefined cutoffs of a quantitative fecal immunochemical test. Deutsches Register Klinischer Studien Identifier: DRKS00003252; EudraCT Identifier: 2011-005603-32/DE.

Low Sensitivity of Fecal Immunochemical Tests and Blood-Based Markers of DNA Hypermethylation for Detection of Sessile Serrated Adenomas/Polyps.

Early detection and removal of precursor lesions reduce colorectal cancer morbidity and mortality. Sessile serrated adenomas/polyps (SSP) are a recognized precursor of cancer, but there are limited studies on whether current screening techniques detect this pathology. To investigate the sensitivity of fecal immunochemical tests (FIT) and epigenetic biomarkers in blood for detection of SSP. A prospective study offered FIT and a blood test (Colvera for methylated BCAT1 and IKZF1) to adults referred for colonoscopy. Sensitivity of FIT and the blood test were determined for four types of pathology: low-risk conventional adenoma, high-risk adenoma, SSP, and absence of neoplasia. Comparisons were made for FIT positivity at 10 and 20μg hemoglobin (Hb)/g feces. One thousand eight hundred and eighty-two subjects completed FIT and underwent colonoscopy. One thousand four hundred and three were also tested for methylated BCAT1/IKZF1. The sensitivity of FIT (20μg Hb/g feces) for SSP was 16.3%. This was lower than the sensitivity for high-risk adenomas (28.7%, p < 0.05), but no different to that for low-risk adenomas (13.1%) or no neoplasia (8.4%). A positive FIT result for SSP was not associated with demographics, morphology, concurrent pathology or intake of medications that increase bleeding risk. FIT sensitivity for SSP did not significantly increase through lowering the positivity threshold to 10μg Hb/g feces (20.4%, p > 0.05). Sensitivity of the blood test for SSP was 8.8%, and 26.5% when combined with FIT. Both FIT and blood-based markers of DNA hypermethylation have low sensitivity for detection of SSP. Further development of sensitive screening tests is warranted.

Microbiota-based model improves the sensitivity of fecal immunochemical test for detecting colonic lesions.

BackgroundColorectal cancer (CRC) is the second leading cause of death among cancers in the United States. Although individuals diagnosed early have a greater than 90 % chance of survival, more than one-third of individuals do not adhere to screening recommendations partly because the standard diagnostics, colonoscopy and sigmoidoscopy, are expensive and invasive. Thus, there is a great need to improve the sensitivity of non-invasive tests to detect early stage cancers and adenomas. Numerous studies have identified shifts in the composition of the gut microbiota associated with the progression of CRC, suggesting that the gut microbiota may represent a reservoir of biomarkers that would complement existing non-invasive methods such as the widely used fecal immunochemical test (FIT).MethodsWe sequenced the 16S rRNA genes from the stool samples of 490 patients. We used the relative abundances of the bacterial populations within each sample to develop a random forest classification model that detects colonic lesions using the relative abundance of gut microbiota and the concentration of hemoglobin in stool.ResultsThe microbiota-based random forest model detected 91.7 % of cancers and 45.5 % of adenomas while FIT alone detected 75.0 % and 15.7 %, respectively. Of the colonic lesions missed by FIT, the model detected 70.0 % of cancers and 37.7 % of adenomas. We confirmed known associations of Porphyromonas assaccharolytica, Peptostreptococcus stomatis, Parvimonas micra, and Fusobacterium nucleatum with CRC. Yet, we found that the loss of potentially beneficial organisms, such as members of the Lachnospiraceae, was more predictive for identifying patients with adenomas when used in combination with FIT.ConclusionsThese findings demonstrate the potential for microbiota analysis to complement existing screening methods to improve detection of colonic lesions.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0290-3) contains supplementary material, which is available to authorized users.

Mo1956 Stage and Site Specific Sensitivity of Fecal Immunochemical Tests for Large Advanced Adenoma and Cancers - A Prospective Multi-National, Multi-Center Study

Mo1956 Stage and Site Specific Sensitivity of Fecal Immunochemical Tests for Large Advanced Adenoma and Cancers - A Prospective Multi-National, Multi-Center Study

Diagnostic Accuracy of a Qualitative Fecal Immunochemical Test Varies With Location of Neoplasia But Not Number of Specimens

We compared the accuracy of a qualitative fecal immunochemical test (FIT) in identifying patients with proximal vs distal advanced neoplasia and evaluated whether analysis of 2 specimens performed better than analysis of 1 specimen. Distal advanced neoplasia was defined as colorectal cancer (CRC), any colorectal adenoma ≥10 mm in diameter, high-grade dysplasia, or a lesion with villous or tubulovillous histologic characteristics in a location distal to the splenic flexure, including the descending colon, the rectosigmoid, and the rectum. We collected data from 5343 subjects (50-70 years old) who received 2 FITs (Hemosure; cutoff value, 10 μg hemoglobin/g feces) before colonoscopy in an invitational CRC screening program in Hong Kong from 2008 through 2012. We calculated the FIT's sensitivity, specificity, positive predictive value (PPV), and negative predictive value in detecting colorectal neoplasia. Of the participants, 13.6%, 12.2%, and 6.0% had distal, proximal, and synchronous distal or proximal neoplasia, respectively. Advanced neoplasia was detected in 291 subjects (5.4%); 22 (0.4%) had CRC. FIT detected distal advanced adenoma with 39.7% sensitivity (95% confidence interval [CI], 32.0%-48.0%) vs proximal advanced adenoma with 25.0% sensitivity (95% CI, 17.3%-34.6%; P = .014), distal advanced neoplasia with 40.0% sensitivity (95% CI, 32.5%-47.9%) vs proximal advanced neoplasia with 27.9% sensitivity (95% CI, 20.0%-37.4%; P = .039), and any distal adenoma ≥10 mm, irrespective of other lesion characteristics, with 39.5% sensitivity (95% CI, 31.0%-48.7%) vs. proximal adenoma with 25.3% sensitivity (95% CI, 16.5%-36.6%; P = .038). The specificity of FIT in detecting CRC was similar between the proximal and distal colon. FIT detected distal lesions with higher PPV than proximal lesions. One FIT detected advanced neoplasia with 31.8% sensitivity (95% CI, 25.9%-38.4%) and 92.4% specificity (95% CI, 91.6%-93.2%), whereas 2 FITs detected advanced neoplasia with 34.1% sensitivity (95% CI, 28.0%-40.8%; P = .617) and 91.9% specificity (95% CI, 91.0%-92.7%; P = .327). FIT detected distal advanced neoplasia with greater sensitivity and higher PPV than proximal advanced neoplasia. In an analysis of data from subjects who underwent CRC screening in Hong Kong, FIT detected distal advanced neoplasia with higher sensitivity than proximal advanced neoplasia. Analysis of 1 vs 2 specimens by FIT identified advanced neoplasia with similar test characteristics.

S1125 Differences in Fit Results Between Screening and Referred Colorectal Cancer Patients are Explained by Differences in Tissue Tumor Stage

Background Fecal immunochemical tests (FITs) are state of the art in colorectal cancer(CRC) screening. Sensitivity of a single FIT for advanced neoplasia is around 50%. Theoretically, as blood loss from colon tumors can be intermittent, sensitivity of FITs could improve by double sampling. This study aims to compare the sensitivity of single FIT sampling and double FIT sampling at different cut-off values, for the detection of advanced neoplasia. Methods All subjects (≥18 years) scheduled for elective colonoscopy in three participating centers in the Amsterdam area were asked to perform FITs (OC sensor®) on two consecutive days. FIT results were compared with colonoscopy and histology as gold standard. Test performance of single FIT was compared to the sensitivity of double FIT sampling. Double FIT sampling was considered positive if one of both FITs was higher than the cut-off value. Test performances were evaluated at cut-off values ranging from 50-150ng/ml (incremental steps of 25ng/ml). Results Of 1105 subjects who performed two FITs and underwent total colonoscopy, 140 (9,4%) had advanced neoplasia (AN), of which 34 were CRC and 106 were advanced adenomas (AA). Of the CRC cases, 70% were Dukes stage A or B (stage unknown in 2). Positivity rates for single FIT ranged from 11-17%, and for double FIT from 14-23%. At the same cut-off value for positivity, sensitivity of double FIT sampling was higher than sensitivity of single FIT sampling. For any particular specificity (e.g. 90%), the sensitivity of double FIT was slightly higher than that of single FIT at a lower cut-off value (see table), but these differences were not statistically significant. Conclusions Two fold sampling of FIT does increase sensitivity for advanced neoplasia. However, at a given specificity, sensitivity of double sampling is comparable to single sampling at a lower cutoff value. Sensitivity and specificity of single and double FIT testing for the detection of advanced neoplasia