Accuracy Of Fecal Immunochemical Test Research Articles

Accuracy, Acceptability, and Application: Fecal Immunochemical Tests for Early Detection of Advanced Neoplasia in Colonoscopy-Based Surveillance.

The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening, but limited data exist for its application in individuals at above-average risk for CRC who complete surveillance colonoscopies. To assess the accuracy, acceptability, and effectiveness of FIT in the interval between surveillance colonoscopies, for predicting advanced neoplasia (advanced adenoma or CRC) at the next colonoscopy. Individuals enrolled in an Australian surveillance program were included. Diagnostic accuracy was determined for 614 individuals completing a two-sample FIT (OC-Sensor) ≤ 3months preceding surveillance colonoscopy. 386 Individuals were surveyed to assess acceptability of interval FIT. Additionally, a retrospective analysis was performed on 7331 individuals offered interval FIT between colonoscopies, where a positive FIT (≥ 20µg hemoglobin/g feces) triggered an early colonoscopy. Associations between interval FIT results and advanced neoplasia were determined using regression analysis. FIT detected CRC and advanced adenoma with sensitivities of 60.0% (3/5) and 27.1% (35/129), respectively. Most (89.1%, 344/386) survey respondents preferred completing interval FIT every 1-2years. The detection rate of interval FIT for advanced neoplasia decreased with increasing FIT completion. Individuals returning a positive FIT had a higher risk of advanced neoplasia than those who did not complete FIT. Positive interval FIT reduced time-to-diagnosis for CRC and advanced adenoma by a median of 30 and 20months, respectively. Interval FIT was well accepted and enabled earlier detection of advanced neoplasia in individuals at above-average risk of CRC. Given that interval FIT predicts advanced neoplasia, it may be used to personalize surveillance colonoscopy intervals.

A107 ANALYSIS OF THE EFFICACY IN TRANSITIONING FROM FOBT TO FIT FOR COLORECTAL CANCER SCREENING AT A SINGLE CENTRE IN ONTARIO

Abstract Background Colonoscopy is the gold standard for detecting colorectal cancer (CRC) and advanced lesions, but is an invasive and carries some risks, with limited availability and accessibility. Alternatively, the fecal occult blood test (FOBT) and fecal immunochemical test (FIT) are both non-invasive, cost-effective screening tests that can also be used to detect CRC, advanced lesions, and polyps, identifying individuals to be prioritized to undergo colonoscopy. FOBT screens for small amounts of blood in stool by detecting heme through a chemical reaction. FIT confirms the presence of blood in stool by using antibodies to detect hemoglobin. Prior to 2019, Ontario employed FOBT as the preferred method for CRC screening in eligible individuals. In early 2019, Ontario transitioned to FIT as the preferred screening test, due its established superior test performance for identifying patients with high risk lesions for colon cancer. Aims This single-centre retrospective study analyzed the change in efficacy of detecting advanced lesions, when transitioning from FOBT to FIT, as identified on subsequent colonoscopy Methods A retrospective chart review was conducted of approximately 1000 patients undergoing colonoscopy for FOBT or FIT at Cambridge Memorial Hospital, covering the period of transition from FOBT to FIT. Colonoscopies were performed by 10 endoscopists. Patients were stratified into 2 groups based on fecal test type, FOBT (N = 344) and FIT (N = 572). Overall and individual proportions of cancer, polyps, adenomas, advanced adenomas (AA), and sessile serrated adenomas (SSA) detection in the subsequent colonoscopies were calculated for both groups. The efficacy of both tests was then assessed using statistical analysis. Results In total, 344 patients were included for FOBT analysis and results included: cancer (5.52%), any polyp (56.69%), adenoma (43.6%), AA (20.64), and SSA (6.1%). In contrast, 572 patients were included for analysis of FIT group and results included: cancer (3.85%), any polyp (83.22%), adenoma (76.92%), AA (43.01), and SSA (12.94%). Cancer detection was similar in the 2 groups. There was significant improvement in polyp, adenoma, advanced adenoma, and sessile serrated adenoma detection with FIT compared to FOBT. This improvement was consistent in all endoscopists, but more pronounced in endoscopists with lower detection rates in FOBT cases. Conclusions The use of FIT as a screening stool test, as compared to FOBT, was associated with a significantly improved detection for polyps, adenomas, AA, and SSA, confirming greater accuracy and sensitivity of FIT as a screening tool. This result confirms the premise, at least at a single institution, that by switching to FIT, Ontario has improved colon cancer screening and prevention with more efficient and higher yield utilization of a limited and costly health care resource Funding Agencies None

'Low' faecal immunochemical test (FIT) colorectal cancer: a 4-year comparison of the Nottingham '4F' protocol with FIT10 in symptomatic patients.

The aim of this work was to evaluate colorectal cancer (CRC) outcomes after 'low' (sub-threshold) faecal immunochemical test (FIT) results in symptomatic patients tested in primary care. This work comprised a retrospective audit of 35 289 patients with FIT results who had consulted their general practitioner with lower gastrointestinal symptoms and had subsequent CRC diagnoses. The Rapid Colorectal Cancer Diagnosis pathway was introduced in November 2017 to allow incorporation of FIT into clinical practice. The local '4F' protocol combined FIT results with blood tests and digital rectal examination (DRE): FIT, full blood count, ferritin and finger [DRE]. The outcome used was detection rates of CRC, missed CRC and time to diagnosis in local 4F protocols for patients with a subthreshold faecal haemoglobin (fHb) result compared with thresholds of 10 and 20 μg Hb/g faeces. A single threshold of 10 μg Hb/g faeces identifies a population in whom the risk of CRC is 0.2%, but this would have missed 63 (10.5%) of 599 CRCs in this population. The Nottingham 4F protocol would have missed fewer CRCs [42 of 599 (7%)] despite using a threshold of 20 μg Hb/g faeces for patients with normal blood tests. Subthreshold FIT results in patients subsequently diagnosed with a palpable rectal tumour yielded the longest delays in diagnosis. A combination of FIT with blood results and DRE (the 4F protocol) reduced the risk of missed or delayed diagnosis. Further studies on the impact of such protocols on the diagnostic accuracy of FIT are expected. The value of adding blood tests to FIT may be restricted to specific parts of the fHb results spectrum.

The Diagnostic Accuracy of a Fecal Immunochemical Test in Detecting Colorectal Cancer and Advanced Precancerous Colorectal Neoplasia in Patients with Iron Deficiency: A Protocol for Systematic Review and Meta-Analysis.

Background. Iron deficiency (ID) is a common micronutrient deficiency and the leading cause of anemia worldwide. ID can be caused by chronic occult blood loss from colorectal neoplasia including colorectal cancer (CRC) and advanced precancerous colorectal lesions. Current guidelines recommend colonoscopy in both men and postmenopausal women presenting with ID anemia (IDA). However, there is controversy on the investigation of patients presenting with a lower risk of CRC including younger women with ID and those with nonanemic ID (NAID). There is a need for a triaging tool to identify which ID patients may benefit from colonoscopy. The fecal immunochemical test (FIT) is sensitive for CRC screening in an asymptomatic population, but its role in ID patients is unclear. The aim of this study is to conduct a systematic review to determine the diagnostic accuracy of FIT for detecting CRC and advanced precancerous neoplasia in individuals presenting with ID with or without anemia. Methods and Analysis. This protocol conforms with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols and Cochrane Handbook for Systematic Reviews of Diagnostic Test Accuracy. A comprehensive search of the MEDLINE, Embase, and Web of Science databases will be undertaken for studies published after 2010 which involve patients with ID, who completed a FIT in the 6 months prior to colonoscopy, with FIT sensitivity and specificity calculated against the reference standard colonoscopy. The search will be limited to studies conducted after 2010 to reduce variability in colonoscopy quality. Risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Accuracy Studies version 2. FIT sensitivity and specificity will be the primary measure of diagnostic accuracy, and data will be analysed using a random effects meta-analysis. Discussion. This review and meta-analysis will be the first to systematically explore the value of the FIT as a triaging tool for patients with ID. This trial is registered with CRD42022367162.

Diagnostic accuracy of risk assessment and fecal immunochemical test in colorectal cancer screening: Results from a population-based program and meta-analysis.

Fecal immunochemical test (FIT) is a commonly used initial test for colorectal cancer (CRC) screening. Parallel use of FIT with risk assessment (RA) could improve the detection of non-bleeding lesions, but at the expense of compromising sensitivity. In this study, we evaluated the accuracy of FIT and/or RA in the Shanghai CRC screening program, and systematically reviewed the relevant evaluations worldwide. RA and 2-specimen FIT were used in parallel in the Shanghai screening program, followed by a colonoscopy among those with positive results. Sensitivity, specificity, detection rate of CRC, positive predictive value (PPV), and other measures with their 95% confident intervals were calculated for each type of tests and several assumed combined tests. We further searched PubMed, Embase, Web of Science, and Cochrane Library for relevant studies published in English up to January 5, 2022. By the end of 2019, a total of 1,901,360 participants of the screening program completed 3,045,108 tests, with 1,901,360 first-time tests and 1,143,748 subsequent tests. Parallel use of RA and 2-specimen FIT achieved a sensitivity of 0.78 (0.77-0.80), a specificity of 0.78 (0.78-0.78), PPV of 0.89% (0.86-0.92), and a detection rate of 1.99 (1.93-2.05) for CRC per 1000 among participants enrolled in the first screening round, and performed similarly among those who participated for several times. A meta-analysis of 103 published observational studies demonstrated a higher sensitivity [0.76 (0.36, 0.94)] but a much lower specificity [0.59 (0.28, 0.85)] of parallel use of RA and FIT for detecting CRC in average-risk populations than in our subjects. One-specimen FIT, the most commonly used initial test, had a pooled specificity comparable to the Shanghai screening program (0.92 vs. 0.91), but a much higher pooled sensitivity (0.76 vs. 0.57). Our results indicate the limitation of FIT only as an initial screening test for CRC in Chinese populations, and highlight the higher sensitivity of parallel use of RA and FIT. Attempts should be made to optimize RA to improve effectiveness of screening in the populations.

Evaluation of Mucosal Healing in Ulcerative Colitis by Fecal Calprotectin vs. Fecal Immunochemical Test: A Systematic Review and Meta-analysis.

Mucosal healing has been considered a treatment goal for patients with inflammatory bowel disease. To compare the accuracy of fecal immunochemical test and fecal calprotectin in the judgment of mucosal healing in ulcerative colitis, a meta-analysis was performed. We searched the PubMed, Cochrane Library, Web of Science, and Embase for the studies on fecal immunochemical test and fecal calprotectin predicting mucosal healing in ulcerative colitis. The comprehensive sensitivity, specificity, diagnostic odds ratio, positive likelihood ratio, and negative likelihood ratio were calculated to evaluate the accuracy. By analyzing 22 publications, we found that the combined sensitivity and specificity of fecal immunochemical test were 0.87 (95% CI, 0.80-0.92) and 0.73 (95% CI, 0.62-0.81), respectively. The combined sensitivity and specificity of fecal calprotectin were 0.76 (95% CI, 0.70-0.80) and 0.80 (95% CI, 0.76-0.84), respectively. The area under the curve values of the fecal immunochemical test and fecal calprotectin summary receiver operating characteristic (SROC) curves were 0.88 and 0.85, respectively. Consequently, fecal immunochemical test had higher sensitivity in predicting mucosal healing in ulcerative colitis patients, while fecal calprotectin had higher specificity. Compared with fecal calprotectin, fecal immunochemical test was more accurate in judging mucosal healing in ulcerative colitis.

Incorporating faecal haemoglobin measurement using the faecal immunochemical test (FIT) in the referral, triage and prioritisation pathway for patients with colorectal symptoms.

To derive a colorectal symptom pathway incorporating standard clinical and FIT data to guide referral, triage, and prioritisation of cases in New Zealand. Diagnostic accuracy of FIT to rule out colorectal cancer (CRC) was determined by meta-analysis. Thereafter, the risk of CRC after FIT was estimated for common clinical presentations by Bayesian methodology, using a specifically collated retrospective cohort of symptomatic cases. A symptom/FIT pathway was developed iteratively following multi-disciplinary engagement. Eighteen studies were included in meta-analysis. The sensitivity and specificity for CRC were 89.0% (95%CI 87.0-90.9%) and 80.1% (95%CI 77.7-82.4%) respectively, at a FHb threshold of >10mcg haemoglobin per gram stool, and 95.7% (95%CI 93.2-97.7%) and 60.5% (95%CI 53.8-67.0%) respectively, at the limit of detection. The final pathway was 97% sensitive for CRC, compared with 90% for the current direct access criteria, and requires 47% fewer colonoscopies. Estimated prevalence of CRC among those declined investigation was 0.23%. Incorporating FIT in the new patient symptomatic pathway as presented appears feasible, safe, and allows for resources to be targeted to those at greatest risk of disease. Further work is needed to ensure equity for Māori if this pathway were introduced nationally.

Diagnostic Accuracy of Fecal Immunochemical Test (FIT) in Bleed-positive and Bleed-negative Colorectal Cancer (CRC) Among a Cohort of 5,090 Subjects who Participated in the Colorectal Neoplasia (CRN) Screening in Brazil.

This study assessed the diagnostic accuracy (DA) of fecal immunochemical test (FIT) ColonView (CV) and guaiac-based fecal occult blood test (HemoccultSENSA) among bleed-positive (history or signs of intestinal bleeding) and bleed-negative participants (no history or signs of intestinal bleeding) (n=5,090) in colorectal neoplasia (CRN) screening in Brazil. The eligible patients for the study (n=506) collected three consecutive stool samples, to be analyzed by both assays (CV, SENSA). Finally, 421/5090 (8.3%) patients returned both samples, which were subjected to final analysis. Receiver operating characteristic (ROC) analysis with different cut-offs was performed to assess the DA. The area under curve (AUC) values for i) visually analyzed (VA) CV for bleed-positive CRC, ii) automatically analyzed (AA) CV for bleed-positive CRC, iii) VA CV for bleed-negative CRC, and iv) AA CV for bleed-negative CRC as endpoints were as follows: i) AUC=0.864, ii) AUC=0.933, iii) AUC=0.836, and iv) AUC=0.892. In roccomp analysis, the differences in AUC values were: between i) and ii) p=0.068; between i) and iii) p=0.497; between i) and iv) p=0.488; between ii) and iii) p=0.0058; between ii) and iv) p=0.229; and between iii) and iv) p=0.138. This is the first investigation where two modes of CV test, VA, and AA, for bleed-positive and bleed-negative CRC patients were used as the endpoint. The AA reading of the CV test showed higher DA in bleed-positive than in bleed-negative CRC patients.

Head-to-Head Diagnostic Test Accuracy Meta-analysis of Colonoscopy and Fecal Immunochemical Test in Detecting Advanced Colon Neoplasia.

Background: Studies on the use of fecal immunochemical test (FIT) in colorectal screening have long assumed perfect accuracy for colonoscopy. No study to date has directly compared the diagnostic accuracy of colonoscopy and FIT to detect advanced neoplasia (AN) in a head-to-head diagnostic accuracy meta-analysis. Methods: A comprehensive electronic search was performed for a head-to-head comparison of FIT and colonoscopy using a third acceptable reference standard in asymptomatic adults. Cochrane methodology was used to perform a head-to-head diagnostic test accuracy (DTA) meta-analysis. Quality assessment tool for diagnostic accuracy studies-2 (QUADAS-2) was used to assess the risk of bias in included studies. Results: Two studies met the eligibility criteria. Overall sensitivity and specificity were 98.5 (95% CI 96.3-100%) and 100% (99.9-100%) for colonoscopy and 16.4% (10.3-22.6%) and 95.4% (94.3-96.4%) for FIT. Colonoscopy was significantly better than FIT (P < 0.0001). The positive and negative likelihood ratios (LRs) were 1.75 (1.57-1.96) and 0.03 (0.01-0.08) for colonoscopy and 3.02 (2.01-4.55) and 0.88 (0.82-0.95) for FIT, respectively. Conclusion: Colonoscopy provides significantly better diagnostic accuracy to detect AN compared with FIT (GRADE: ⨁⨁◯◯). Our study provided precise sensitivity and specificity of both colonoscopy and FIT and a revision in screening policies based on an updated cost-effectiveness analysis considering the results of the head-to-head analysis.

Potential Modifiers and Different Cut-offs in Diagnostic Accuracy of Fecal Immunochemical Test in Detecting Advanced Colon Neoplasia: A Diagnostic Test Accuracy Meta-analysis.

Background: Fecal immunoglobulin test (FIT) has been advocated as the first line of screening for colorectal cancer (CRC) in several jurisdictions. Most studies have focused on CRC as the outcome of interest. Our goal was to quantify the diagnostic accuracy of different thresholds of FIT as compared with colonoscopy for detection of advanced colonic neoplasia and potential modifiers using proper Cochrane methodology. Methods: A comprehensive electronic search was performed for studies on FIT using colonoscopy as the reference standard to detect advanced neoplasia. Cochrane methodology was used to perform a diagnostic test accuracy (DTA) meta-analysis. Diagnostic accuracy of different cut-offs of FIT, including 25, 50, 75, 100, 150, and 200 ng/mL, were calculated separately. Meta-regression analysis was also performed to detect potential a priori modifiers, including age, location of the tumor, and time from FIT to colonoscopy. Results: Twenty-four studies were included with no evidence of publication bias. The sensitivity of FIT did not decrease with lowering the cut-off, although specificity increased in higher cut-offs. Commonly used cut-offs of 50 ng/mL, 75 ng/mL, and 100 ng/mL for FIT provided sensitivity of 39%, 36%, 27% and specificity of 92%, 94%, 96%, respectively. Diagnostic accuracy of FIT did not significantly differ in proximal versus distal lesions or in individuals below or over the age of 50 years. The results remained robust in a meta-regression of the location of the study, time from FIT to colonoscopy, and methodological quality. Conclusion: The sensitivity of FIT might have been overestimated in previous studies focusing on CRC, and it seems to be independent of age, location of neoplasia, or cut-offs, contrary to some previous studies. Lowering the cut-off will reduce the diagnostic odds ratio (DOR) by increasing specificity but without any effect on sensitivity.

Role of the faecal immunochemical test in patients with risk-stratified suspected colorectal cancer symptoms: A systematic review and meta-analysis to inform the ACPGBI/BSG guidelines.

SummaryBackgroundThe UK National Institute for Health and Care Excellence (NICE), recommended in 2017 the use of the faecal immunochemical test (FIT) to guide investigations in patients presenting with NICE-defined low-risk symptoms suspicious for colorectal cancer (CRC). At that time, NICE did not recommend FIT use for high-risk symptoms. This is the first systematic review to evaluate the diagnostic accuracy of FIT in NICE-defined high and low-risk symptoms and was designed to inform the joint ACPGBI/BSG guidelines.MethodsWe performed a systematic literature review and meta-analysis. PROSPERO registration number CRD42021224674. Medline and EMBASE databases were searched from inception to 31st March 2022. We included studies recruiting adult patients presenting with suspected CRC symptoms in whom FIT was performed and diagnostic accuracy data for CRC detection could be derived at a limit of detection (LoD) and/or 10 µg haemoglobin/gram faeces threshold in four commonly used analysers. FIT performance was assessed for high-risk, low-risk and individual symptoms where possible. Bivariate meta-analysis was performed where study numbers allowed.FindingsThirty-one studies (79566 patients) met inclusion criteria. At 10 µg/g, for “all symptoms” (n = 35,945) sensitivity and specificity were 91.0% (95% CI: 88.9, 92.7) and 75.2% (95% CI: 69.6, 80.1); for “high-risk” symptoms (n = 18,264), 88.7% (95% CI: 84.4, 92.0) and 78.5% (95% CI: 73.0, 83.2); and for “low-risk” symptoms (n = 2161), 88.7% (95% CI: 78.1, 95.3) and 88.5% (95% CI: 87.1, 89.9), respectively. At LoD, for “all symptoms” (n = 26,056) sensitivity and specificity were 94.7% (95% CI: 90.5, 97.1) and 66.5% (95% CI: 58.7, 73.6); for “high-risk” symptoms (n = 16,768), 92.8% (95% CI: 86.4, 96.3) and 70.3% (95% CI: 66.5, 73.8); and for “low-risk” symptoms (n = 2082), 94.7% (95% CI: 85.4, 98.9) and 71.9% (95% CI: 69.9, 73.9), respectively. Summary estimates were similar across different analysers.InterpretationFIT sensitivity for CRC detection is maximised at the LoD; its performance is similar in high and low-risk symptoms, and across different analysers where a common threshold is used. FIT performance for CRC detection is adequate and transferrable to clinical diagnostic pathways.FundingThis review was part-funded by NHS England awarded to RM Partners. RB and RC were funded by research fellowships awarded by Croydon University Hospital.

Fecal Immunochemical Testing in Patients With Low-Risk Symptoms of Colorectal Cancer: A Diagnostic Accuracy Study.

The fecal immunochemical test (FIT) is recommended for triaging primary care patients in England with low-risk symptoms of colorectal cancer (CRC). The evidence underpinning recommendations by the National Institute for Health and Care Excellence had limitations, with a paucity of primary care evidence. This study examines the diagnostic accuracy of FIT in a defined low-risk symptom primary care population. Consecutive symptomatic adult patients referred for a FIT between October and December 2019 were included. Patients were derived from 225 primary care practices in England. Serious colorectal diseases (CRC, high-risk polyps, and inflammatory bowel disease [IBD]) were identified through patient follow-up over 18 months, using both primary and secondary healthcare records. Performance characteristics of FIT are reported according to differing thresholds, including the currently recommended threshold of ≥10 μg hemoglobin per gram of feces (μg/g). A total of 3,506 patients were included in the final analysis. Of these, 708 had a positive FIT result (≥10 μg/g). The prevalence of CRC was 1.3%. FIT positivity declined from 20.2% to 5.8% and 4.5% at cutoffs of 10, 80, and 120 μg/g, respectively. The sensitivity of FIT at ≥10 μg/g to detect CRC was 91.1% (95% CI, 77.9%-97.1%); its specificity was 80.7% (95% CI, 79.3%-82.0%); the positive predictive value (PPV) was 5.8% (95% CI, 4.2%-7.8%); and the negative predictive value (NPV) was 99.9% (95% CI, 99.6%-99.95%). The area under the receiver operating characteristic curve was 0.93 (0.91-0.96). PPV and specificity increased, whereas sensitivity and NPV decreased when serious colorectal diseases (CRC, high-risk polyps, and IBD) were combined. Age, sex, socioeconomic deprivation, and anemia did not significantly influence FIT sensitivity on subgroup analysis. Utilization of FIT at a threshold ≥10 μg/g can safely triage patients with low-risk symptoms in primary care, with negative results effectively ruling out CRC.

The Accuracy of Fecal Immunochemical Test in Colorectal Cancer Screening: A Meta-Analysis.

Objective:To investigate the accuracy of OC-Sensor and colorectal cancer screening in a population-based randomized controlled trial at Khon Kaen province, Thailand. Methods:The MOOSE Guidelines for Systematic Reviews and Meta-Analyses of Observational Studies was applied. Eligibility criteria were English language, hand searching was conducted using Medline databases from 2010 to 2021 for identify literatures reviews of OC-Sensor and colorectal cancer screening. The initials screen based on the research titles and abstracts, final screenings based on full-text reports. Synthesis the results with meta-analysis using fixed effect model, random effect model, determined statistically significant with p-value < 0.05. Confirmed the pooled effect sizes of high heterogeneity by meta-regression including tested precision of each estimates by bubble plot using STATA version 14. Results:Meta-regression showed sensitivity of OC- sensor = 72.54% (95% CI: 65.82-79.25), and specificity of OC- sensor = 89.59% (95% CI: 87.23-91.95).Conclusions:Sample size and cut-off of fecal hemoglobin concentration in each study were differed but sub-group analysis and sensitivity analysis were not considered for this analysis because population, setting and location for detected cancer of included study are not differences.

S326 Potential Modifiers and Different Cut-offs in Diagnostic Accuracy of Fecal Immunochemical Test in Detecting Advanced Colon Neoplasia: A Diagnostic Test Accuracy Meta-Analysis

Introduction: Fecal Immunoglobulin Test (FIT) has been advocated as the first line of screening for colorectal cancer in several jurisdictions. Most studies have focused on colorectal cancer as the outcome of interest. Our goal was to quantify the diagnostic accuracy of different threshold of fecal immunochemical testing as compared to colonoscopy for detection of colonic advanced neoplasia and potential modifiers using proper Cochrane methodology. Methods: A comprehensive electronic search was performed for studies on FIT using colonoscopy as reference standard, to detect advanced neoplasia. Cochrane methodology was used to perform a diagnostic test accuracy meta-analysis. Diagnostic accuracy of different cut-offs of FIT including 25, 50, 75, 100, 150 and 200 ng/mL were calculated separately. Meta-regression analysis was also performed to detect potential a priori modifiers including age, location of tumour, time from FIT to colonoscopy. Results: 24 studies were included with no evidence of publication-bias. Sensitivity of FIT did not decrease with lowering the cut-off although specificity increased in higher cut-offs. Commonly used cut-offs of 50 ng/mL, 75 ng/mL and 100 ng/mL for FIT provided sensitivity of 39%, 36%, 27% and specificity of 92%, 94%, 96%, respectively. The sensitivity and specificity of FIT were 31 (26-36)% and 95 (94-96)%, respectively for distal lesions and 20 (13-27)% and 95 (94-96)%, respectively for proximal lesions (P=0.16). These numbers were 18 (3 - 33)% and 97 (96 - 98)%, respectively in those older than 50 as compared to 10 (1 - 19)% and 98 (97 - 99)%, respectively, for those under 50 (P=0.47). Meta-regression analysis did not show any significant predictability for location of the study (Asian versus non-Asian, P=0.06), inclusion of patients with unclear or high risk (P=0.14), time gap from FIT to colonoscopy (P=0.09) and risk of bias (high or unclear as compared to low) criteria in diagnostic accuracy of FIT (P=0.82). Conclusion: Sensitivity of FIT might have been overestimated in previous studies focusing on colorectal cancer as compared to advanced neoplasia and it seems to be independent of age, location of neoplasia or cut-offs contrary to some previous studies. Lowering the cut-off will reduce diagnostic odds ratio by increasing specificity but without any effect on sensitivity.Figure 1.: SROC of diagnostic accuracy of colonoscopy and different cut-offs of FIT.Table 1.: Diagnostic test accuracy of FIT for most used cut-off.

Performance of the faecal immunochemical test for the detection of colorectal neoplasms and the role of proton pump inhibitors in their diagnostic accuracy.

The faecal immunochemical test (FIT) is currently utilized in both symptomatic and screening populations, but little is known about factors that affect its performance. For example, proton pump inhibitor (PPI) therapy has been purported to increase false negative rates. This has significant implications given the extent of PPI prescriptions. The aim of this work was to evaluate the performance of the FIT for the detection of colorectal neoplasms and the impact of PPI therapy on its diagnostic accuracy. Symptomatic patients referred on the suspected cancer pathway and those on polyp surveillance between 2015 and 2019 were approached to participate. Estimates of the accuracy of FIT at different cut-off levels in diagnosing colorectal neoplasms were made. Logistic regression was used to assess the effect of PPIs on the FIT results. A total of 667 participants were eligible for the final analysis. At a cut-off of 10μg/g faeces, the overall sensitivity and specificity of FIT for the detection of colorectal cancer (CRC) was 0.85 (95% CI 0.71-0.94) and 0.81 (95% CI 0.78-0.84), respectively. For the detection of advanced neoplasia, the sensitivity was 0.70 (95% CI 0.58-0.79) and the specificity was 0.83 (95% CI 0.80-0.86). At higher thresholds, the sensitivity steadily declined whilst specificity increased. PPI therapy did not have a significant effect on performance of the FIT. FIT is a good rule-out test for the detection of CRC and advanced neoplasia at lower thresholds. PPI therapy does not appear to have an effect on its diagnostic performance.

Systematic review with meta-analysis: volatile organic compound analysis to improve faecal immunochemical testing in the detection of colorectal cancer.

Faecal immunochemical test (FIT) is emerging as a valid test to rule-out the presence of colorectal cancer (CRC). However, the accuracy of FIT is dependent on the cut-off applied. An additional low-cost test could improve further detection of CRC. To evaluate the efficacy of combined FIT and volatile organic compounds (VOC) in the detection of CRC within symptomatic populations. Systematic reviews on the diagnostic accuracy of FIT and VOC, for the detection of CRC, were updated. Meta-analyses were performed adopting a bivariate model for sensitivity and specificity. Clinical utility of combined FIT and VOC was estimated using Fagan's nomogram. Post-test probability of FIT negatives was used as a pre-test probability for VOC. The pooled sensitivity and specificity of FIT at 10µg/g faeces, for the detection of CRC, were 0.914 (95% confidence interval [CI]=0.894-0.936) and 0.783 (CI=0.850-0.696), respectively. For VOC, the sensitivity was 0.837 (CI=0.781-0.881) and the specificity was 0.803 (CI=0.870-0.712). The area under the curve for FIT and VOC were 0.926 and 0.885, respectively. In a population with 5% CRC prevalence, the estimated probability of having CRC following a negative FIT was 0.5% and following both negative FIT and VOC was 0.1%. In a FIT-negative symptomatic population, VOC can be a good test to rule-out the presence of CRC. The estimated probability reduction by 0.4% when both tests being negative offers adequate safety netting in primary care for the exclusion of CRC. The number needed to colonoscope to identify one CRC is eight if either FIT or VOC positive. Cost-effectiveness and clinical accuracy of this approach will need further evaluation.

The American Society of Colon and Rectal Surgeons 2021 Annual Scientific Meeting Abstracts

Purpose/Background: Faecal immunochemical test (FIT) is widely adopted for the screening of colorectal cancer in the United Kingdom. At the start of the coronavirus pandemic we incorporated FIT testing into our department's urgent referral pathway for patients with suspected colorectal cancer. This aimed to triage those symptomatic patients who required urgent investigation and those who were unlikely to have significant colorectal pathology and therefore could have investigations delayed until it was safer and endoscopy services had recovered capacity. This study aimed to identify the diagnostic accuracy of FIT in this setting. Methods/Interventions: Patients referred to our institution under our urgent cancer referral pathway between 28th April and 19th June 2020 were identified from a prospectively kept database. FIT results were accessed from electronic laboratory records. Results were analysed using a threshold of 10ug/ml and the current screening threshold in England of 120ug/ml. Patient outcomes were determined by electronic patient records. Significant polyps included polyps greater than 10mm or meeting British Society of Gastroenterology high risk criteria. Results/Outcome(s): 373 patients were referred to the colorectal department during the study period. 24 referrals did not meet urgent referral criteria. 202 (54%) patients had FIT performed by their general practitioner and 47 (13%) patients had FIT undertaken in the colorectal clinic. In patients who had FIT, 97 (41%) patients had a FIT result less than 10ug/ml and 193 (81%) patients had FIT less than 120ug/ml. 25 (10%) patients were not investigated further based on FIT result and 16 (6%) patients declined further investigation. 13 (3%) patients in the cohort were subsequently investigated and diagnosed with a colorectal cancer (FIT range 24-8438ug/ml). One patient was diagnosed with a gastric cancer (FIT 259ug/ml) and two other patients had incidental findings of other nongastrointestinal cancers. 9 (4%) and 19 (8%) patients had significant colonic polyps and colitis respectively. Other diagnoses included bleeding gastric ulcer (2), angiodysplasia (1) and solitary rectal ulcer syndrome (1). In this symptomatic cohort, with a threshold of 10ug/ml the sensitivity of FIT was 100% and specificity of 36% for the diagnosis of colorectal cancer. At the 120ug/ml threshold the sensitivity was 77% and the specificity 81% for the diagnosis of colorectal cancer. Conclusions/Discussion: Incorporating FIT to triage symptomatic patients with symptoms suggestive of colorectal cancer is feasible with acceptable levels of diagnostic accuracy when utilizing a threshold of 10ug/ml. FIT testing will continue to be incorporated into our urgent cancer referral pathway, although general practitioners may still refer patients with a negative FIT but high clinical suspicion. Further work will continue to audit the use of FIT in this symptomatic setting.

The Fast Track FIT study: diagnostic accuracy of faecal immunochemical test for haemoglobin in patients with suspected colorectal cancer.

BackgroundThe faecal immunochemical test (FIT) is now available to support clinicians in the assessment of patients at low risk of colorectal cancer (CRC) and within the bowel cancer screening programme.AimTo determine the diagnostic accuracy of FIT for CRC and clinically significant disease in patients referred as they were judged by their GP to fulfil National Institute for Health and Care Excellence guideline 12 (NG12) criteria for suspected CRC.Design and settingPatients referred from primary care with suspected CRC, meeting NG12 criteria, to 12 secondary care providers in Yorkshire and Humber were asked to complete a FIT before investigation.MethodThe diagnostic accuracy of FIT based on final diagnosis was evaluated using receiver operating characteristics analysis. This permitted a statistically optimal cut-off value for FIT to be determined based on the maximisation of sensitivity and specificity. Clinicians and patients were blinded to the FIT results.ResultsIn total, 5040 patients were fully evaluated and CRC was detected in 151 (3.0%). An optimal cut-off value of 19 µg Hb/g faeces for CRC was determined, giving a sensitivity of 85.4% (95% confidence interval [CI] = 78.8% to 90.6%) and specificity of 85.2% (95% CI = 84.1% to 86.2%). The negative predictive value at this cut-off value was 99.5% (95% CI = 99.2% to 99.7%) and the positive predictive value 15.1% (95% CI = 12.8% to 17.7%). Sensitivity and specificity of FIT for CRC and significant premalignant polyps at this cut-off value were 62.9% (95% CI = 57.5% to 68.0%) and 86.4% (95% CI = 85.4% to 87.4%), respectively; and when including all organic enteric disease were 35.7% (95% CI = 32.9% to 38.5%) and 88.6% (95% CI = 87.5% to 89.6%), respectively.ConclusionFIT used in patients fulfilling NG12 criteria should allow for a more personalised CRC risk assessment. FIT should permit effective, patient-centred decision-making to inform the need for, type, and timing of further investigation.

Effects of antithrombotic drugs on the results of fecal immunochemical test in colorectal neoplasms screening

Fecal immunochemical test (FIT) is widely used as a colorectal cancer screening tool. Antithrombotic drugs may affect the screening performance of FIT for colorectal tumors. The aim of this study was to clarify the effect of antithrombotic agents on FIT accuracy in screening for colorectal neoplasms. This retrospective study enrolled a total of 758 patients who underwent both FIT and total colonoscopy. The effect of antithrombotic drugs on FIT accuracy in detecting colorectal neoplasms (CN), including colorectal cancer (CRC), advanced adenoma (AA), and non-advanced adenoma (NAA), was examined. Of the 758 patients, 144 (19%) received antithrombotic drugs (administration group). In administration group, 61/144 (42%) cases had CN [CRC:14, AA:15, NAA:32] and 217/614 (35%) cases had CN (CRC:43, AA:56, NAA:118) in non-administration group. The prevalence of CN was not significantly different between the two groups (p = 0.1157). There was no significant difference in sensitivity or specificity of the detection of all types of CN with or without taking antithrombotic drugs. Neither the positive predictive value nor negative predictive value of FIT was affected by antithrombotic drug administration. Taking antithrombotic drugs may not have a large impact on sensitivity, specificity, positive predictive value, or negative predictive value of FIT in screening for CN.

Predictive Value of Carcinoembryonic Antigen in Symptomatic Patients without Colorectal Cancer: A Post-Hoc Analysis within the COLONPREDICT Cohort.

We aimed to assess the risk of cancer in patients with abdominal symptoms after a complete colonoscopy without colorectal cancer (CRC), according to the carcinoembryonic antigen (CEA) concentration, as well as its diagnostic accuracy. For this purpose, we performed a post-hoc analysis within a cohort of 1431 patients from the COLONPREDICT study, prospectively designed to assess the fecal immunochemical test accuracy in detecting CRC. Over 36.5 ± 8.4 months, cancer was detected in 115 (8%) patients. Patients with CEA values higher than 3 ng/mL revealed an increased risk of cancer (HR 2.0, 95% CI 1.3–3.1), CRC (HR 4.4, 95% CI 1.1–17.7) and non-gastrointestinal cancer (HR 1.7, 95% CI 1.0–2.8). A new malignancy was detected in 51 (3.6%) patients during the first year and three variables were independently associated: anemia (OR 2.8, 95% CI 1.3–5.8), rectal bleeding (OR 0.3, 95% CI 0.1–0.7) and CEA level >3 ng/mL (OR 3.4, 95% CI 1.7–7.1). However, CEA was increased only in 31.8% (95% CI, 16.4–52.7%) and 50% (95% CI, 25.4–74.6%) of patients with and without anemia, respectively, who would be diagnosed with cancer during the first year of follow-up. On the basis of this information, CEA should not be used to assist in the triage of patients presenting with lower bowel symptoms who have recently been ruled out a CRC.