Quantitative Fecal Immunochemical Test Research Articles

Setting up a service for a faecal immunochemical test for haemoglobin (FIT): a review of considerations, challenges and constraints

Quantitative faecal immunochemical tests for haemoglobin (FIT) have now been advocated by the National Institute for Care and Health Excellence (NICE: DG30) to assist in the triage of patients presenting...

Influence of Varying Quantitative Fecal Immunochemical Test Positivity Thresholds on Colorectal Cancer Detection: A Community-Based Cohort Study.

The fecal immunochemical test (FIT) is commonly used for colorectal cancer (CRC) screening. Despite demographic variations in stool hemoglobin concentrations, few data exist regarding optimal positivity thresholds by age and sex. To identify programmatic (multitest) FIT performance characteristics and optimal FIT quantitative hemoglobin positivity thresholds in a large, population-based, screening program. Retrospective cohort study. Kaiser Permanente Northern and Southern California. Adults aged 50 to 75 years who were eligible for screening and had baseline quantitative FIT results (2013 to 2014) and 2 years of follow-up. Nearly two thirds (411241) had FIT screening in the previous 2 years. FIT programmatic sensitivity for CRC and number of positive test results per cancer case detected, overall and by age and sex. Of 640859 persons who completed a baseline FIT and were followed for 2 years, 481817 (75%) had at least 1 additional FIT and 1245 (0.19%) received a CRC diagnosis. Cancer detection (programmatic sensitivity) increased at lower positivity thresholds, from 822 in 1245 (66.0%) at 30 µg/g to 925 (74.3%) at 20 µg/g and 987 (79.3%) at 10 µg/g; the number of positive test results per cancer case detected increased from 43 at 30 µg/g to 52 at 20 µg/g and 85 at 10 µg/g. Reducing the positivity threshold from 20 to 15 µg/g would detect 3% more cancer cases and require 23% more colonoscopies. At the conventional FIT threshold of 20 µg/g, programmatic sensitivity decreased with increasing age (79.0%, 73.4%, and 68.9% for ages 50 to 59, 60 to 69, and 70 to 75 years, respectively; P= 0.009) and was higher in men than women (77.0% vs. 70.6%; P= 0.011). Information on advanced adenoma was lacking. Increased cancer detection at lower positivity thresholds is counterbalanced by substantial increases in positive tests. Tailored thresholds may provide screening benefits that are more equal among different demographic groups, depending on local resources. National Cancer Institute.

Accuracy of a fecal immunochemical test according to outside temperature and travel time.

BackgroundFecal immunochemical tests (FITs) are widely used and recommended for colorectal cancer (CRC) screening. Fecal hemoglobin (Hb) may degrade with long transport durations and high ambient temperatures, potentially reducing sensitivity to detect CRC and its precursors. This study aimed at investigating the impact of temperatures and sample travel times on diagnostic performance of a quantitative FIT for detection of advanced neoplasms (AN, CRC, or advanced adenoma).MethodsParticipants of screening colonoscopy in south-western Germany conducted a quantitative FIT prior to bowel preparation between February 2012 and June 2016. From available locations and dates of stool sampling and transport, maximum ambient temperatures were linked to 2,870 participants aged 50–79 years and sample return durations were recorded. The impact of ambient temperatures and return duration on FIT sensitivity and specificity was assessed for five different cutoffs between 10 and 25 µg Hb/g feces.ResultsAt a positivity threshold of 20 µg Hb/g feces, overall sensitivity and specificity for detecting any AN were 40% (95% CI, 35–47%) and 95% (95% CI, 94–96%), respectively. Inverse associations between maximum ambient temperature (median 18.1°C, inter-quartile range [IQR] =11.4–24.9°C) and sensitivity of FIT were observed which were stronger at higher cutoffs. Sample return durations (median 6 days, IQR =4–8 days) were not associated with variable sensitivities or specificities.ConclusionHb degredation during fecal sample transportation in summer months may be of some concern for diagnostic performance of the FIT evaluated under routine conditions in a middle-European climate.

Risk stratification for colorectal neoplasia detection in the Flemish colorectal cancer screening programme

BackgroundThe quantitative faecal immunochemical test (FIT) detects pre-cancerous lesions and colorectal cancer (CRC). Current CRC screening programmes are based upon a binary FIT result. This study evaluates the possibility of personalised risk prediction, based on FIT, age and gender to gain more insight into improving discrimination between normal outcomes, pre-cancerous lesions, carcinoma in situ and CRC working towards a more tailored screening approach. MethodsIn this retrospective study, from October 2013 until July 2016, data from 57,421 participants who underwent a colonoscopy after a positive FIT in the Flemish CRC screening programme were analysed using a multinomial multivariable logistic regression model. ResultsA significant difference in risk of detecting neoplasia was found between the established risk profiles based on the combination of the quantitative FIT, age and gender. The odds for detecting CRC in men aged 74, with a FIT result of ≥1000 ng/ml, was higher by a factor of 58.43 than that for women aged 56, with a FIT result of 75 ng/ml. ConclusionA large difference in risk with regard to the detection of colorectal neoplasia was found, based on demographics of the population. For some participants, the chance of finding no anomalies was more than 60%. Including additional variables in a prediction model could further increase discrimination between outcomes and practicality.

Equivalent Accuracy of 2 Quantitative Fecal Immunochemical Tests in Detecting Advanced Neoplasia in an Organized Colorectal Cancer Screening Program

Although different brands of fecal immunochemical tests (FITs) are used for colorectal cancer (CRC) screening, few studies have compared their accuracy in detecting advanced neoplasia. We performed a large prospective cohort study within the Dutch national CRC screening program to evaluate 2 quantitative FITs: FOB-Gold (Sentinel, Milan, Italy) and OC-Sensor (Eiken Chemical, Tokyo Japan), from May 2016 through March 2017. We randomly selected 42,179 screening-naïve individuals (55-75 years old), who were asked to perform both FITs themselves using the same bowel movement. Participants with positive results from 1 or both FITs (≥15 μg hemoglobin/gram feces) were invited for colonoscopy examination (reference standard). Equivalence in detection of advanced neoplasia was evaluated with a predefined margin of 0.15%. Of 42,179 invitees, 22,064 (52%) participated and FITs were completed for 21,078 participants. Of 2112 participants (9.6%) with 1 or 2 positive results from FITs, 1778 (84%) underwent a colonoscopy. Of all invitees, the FOB-Gold test detected advanced neoplasia (confirmed by colonoscopy) in 610 participants (1.45%) and the OC-Sensor detected advanced neoplasia (confirmed by colonoscopy) in 606 participants (1.44%)-an absolute difference of 0.01% (95% confidence interval [CI], -0.06% to 0.08%). Of the 21,078 participants who completed both FITs, 1582 (7.5%) had a positive result from the FOB-Gold test and 1627 (7.7%) a positive result from the OC-Sensor test (P= .140). The relative true-positive rate of FOB-Gold vs OC-Sensor in detecting advanced neoplasia was 0.97 (95% CI, 0.92-1.01) and 0.95 (95% CI, 0.87-1.03) for CRC. The relative false-positive rate of the FOB-Gold test vs the OC-Sensor test in detecting advanced neoplasia was 0.99 (95% CI, 0.93-1.05). In a large prospective study of individuals invited for CRC screening in The Netherlands, we found equivalent accuracy of the FOB-Gold FIT vs the OC-Sensor FIT in detecting advanced neoplasia. These results are relevant for selecting FITs for CRC screening programs worldwide. Dutch National Trial Registry: NTR5874.

Detection capability of quantitative faecal immunochemical tests for haemoglobin (FIT) and reporting of low faecal haemoglobin concentrations.

Faecal immunochemical tests for haemoglobin (FIT) are widely used in asymptomatic population screening for colorectal (bowel) cancer. FIT are also used to assist with the assessment of patients presenting with lower abdominal symptoms. Quantitative FIT allow the generation of numerical estimates of faecal haemoglobin (f-Hb) concentrations. There is now great interest in "low" f-Hb concentrations in these clinical settings: in consequence, knowledge of the detection capability is very important for f-Hb concentration examinations. There are a number of current problems associated with the reporting of low f-Hb concentrations and wide misunderstanding of the metrological aspects of examinations of f-Hb at low concentrations. These would be solved if the detectability characteristics of f-Hb concentration examinations, namely, the limit of blank (LoB), limit of detection (LoD) and limit of quantitation (LoQ), were generated, validated and used in reporting systems exactly as recommended in the EP17-A2 guideline of the Clinical Laboratory Standards Institute. LoB and LoD are statistical concepts, but the LoQ depends on definition of analytical performance specifications (APS). In this Opinion Paper proposals for interim APS are made, based on the current state of the art achieved with examinations of faecal samples. It is proposed that LoQ is determined at an examination imprecision of CV≤10% using faecal samples naturally positive for Hb rather than faeces spiked with haemolysate. Detailed proposals for reporting f-Hb data at low concentrations are also made.

Demand for Colonoscopy in Colorectal Cancer Screening Using a Quantitative Fecal Immunochemical Test and Age/Sex-Specific Thresholds for Test Positivity.

Background: Despite age and sex differences in fecal hemoglobin (f-Hb) concentrations, most fecal immunochemical test (FIT) screening programs use population-average cut-points for test positivity. The impact of age/sex-specific threshold on FIT accuracy and colonoscopy demand for colorectal cancer screening are unknown.Methods: Using data from 723,113 participants enrolled in a Taiwanese population-based colorectal cancer screening with single FIT between 2004 and 2009, sensitivity and specificity were estimated for various f-Hb thresholds for test positivity. This included estimates based on a "universal" threshold, receiver-operating-characteristic curve-derived threshold, targeted sensitivity, targeted false-positive rate, and a colonoscopy-capacity-adjusted method integrating colonoscopy workload with and without age/sex adjustments.Results: Optimal age/sex-specific thresholds were found to be equal to or lower than the universal 20 μg Hb/g threshold. For older males, a higher threshold (24 μg Hb/g) was identified using a 5% false-positive rate. Importantly, a nonlinear relationship was observed between sensitivity and colonoscopy workload with workload rising disproportionately to sensitivity at 16 μg Hb/g. At this "colonoscopy-capacity-adjusted" threshold, the test positivity (colonoscopy workload) was 4.67% and sensitivity was 79.5%, compared with a lower 4.0% workload and a lower 78.7% sensitivity using 20 μg Hb/g. When constrained on capacity, age/sex-adjusted estimates were generally lower. However, optimizing age/-sex-adjusted thresholds increased colonoscopy demand across models by 17% or greater compared with a universal threshold.Conclusions: Age/sex-specific thresholds improve FIT accuracy with modest increases in colonoscopy demand.Impact: Colonoscopy-capacity-adjusted and age/sex-specific f-Hb thresholds may be useful in optimizing individual screening programs based on detection accuracy, population characteristics, and clinical capacity. Cancer Epidemiol Biomarkers Prev; 27(6); 704-9. ©2018 AACR.

Performance of a quantitative fecal immunochemical test for detecting advanced colorectal neoplasia: a prospective cohort study

BackgroundThe fecal immunochemical test (FIT) is easier to use and more sensitive than the guaiac fecal occult blood test, but it is unclear how to optimize FIT performance. We compared the sensitivity and specificity for detecting advanced colorectal neoplasia between single-sample (1-FIT) and two-sample (2-FIT) FIT protocols at a range of hemoglobin concentration cutoffs for a positive test.MethodsWe recruited 2,761 average-risk men and women ages 49-75 referred for colonoscopy within a large nonprofit, group-model health maintenance organization (HMO), and asked them to complete two separate single-sample FITs. We generated receiver-operating characteristic (ROC) curves to compare sensitivity and specificity estimates for 1-FIT and 2-FIT protocols among those who completed both FIT kits and colonoscopy. We similarly compared sensitivity and specificity between hemoglobin concentration cutoffs for a single-sample FIT.ResultsDifferences in sensitivity and specificity between the 1-FIT and 2-FIT protocols were not statistically significant at any of the pre-specified hemoglobin concentration cutoffs (10, 15, 20, 25, and 30 μg/g). There was a significant difference in test performance of the one-sample FIT between 50 ng/ml (10 μg/g) and each of the higher pre-specified cutoffs. Disease prevalence was low.ConclusionsA two-sample FIT is not superior to a one-sample FIT in detection of advanced adenomas; the one-sample FIT at a hemoglobin concentration cutoff of 50 ng/ml (10 μg/g) is significantly more sensitive for advanced adenomas than at higher cutoffs. These findings apply to a population of younger, average-risk patients in a U.S. integrated care system with high rates of prior screening.

Mo1606 - Influence of Varying Quantitative Fecal Immunochemical Test Cut-offs on Sensitivity and Specificity for Colorectal Cancer Detection: A Community-Based Cohort Study

Mo1606 - Influence of Varying Quantitative Fecal Immunochemical Test Cut-offs on Sensitivity and Specificity for Colorectal Cancer Detection: A Community-Based Cohort Study

Diagnostic Performance of One-off Flexible Sigmoidoscopy with Fecal Immunochemical Testing in a Large Screening Population.

Flexible sigmoidoscopy and fecal immunochemical tests are established diagnostic tests for colorectal cancer (CRC) screening and less invasive, less expensive, and easier to conduct than colonoscopy. However, little is known about their joint diagnostic performance compared with colonoscopy. We aimed to assess the expected diagnostic performance of joint use of flexible sigmoidoscopy and fecal immunochemical test. We assessed the overall and site-specific prevalences of colorectal neoplasms and the overall sensitivity, specificity, area under the receiver operating characteristics curve of a quantitative fecal immunochemical test (FOB Gold, Sentinel Diagnostics, Milano, Italy) among 3,466 participants in screening colonoscopy in Germany. Results were used to model the expected diagnostic performance of joint use of flexible sigmoidoscopy and fecal immunochemical testing. CRC and advanced adenomas were found in 29 (1%) and 354 (10%) participants, respectively. The area under the curve of fecal immunochemical testing for these outcomes could be raised from 96% to 100% and from 70% to 89%, respectively, by combining it with flexible sigmoidoscopy. At 90% specificity, sensitivity of fecal immunochemical testing would increase from 97% to 100% for CRC and from 40% to 79% for advanced adenomas. Combining flexible sigmoidoscopy and fecal immunochemical testing might strongly enhance diagnostic performance of each single test to a level close to the diagnostic performance of screening colonoscopy while avoiding many unnecessary colonoscopies.

Risk of Interval Cancer in Fecal Immunochemical Test Screening Significantly Higher During the Summer Months: Results from the National Cancer Screening Program in Korea.

This study aimed to evaluate the impact of seasonal variations in climate on the performance of the fecal immunochemical test (FIT) in screening for colorectal cancer in the National Cancer Screening Program in Korea. Data were extracted from the National Cancer Screening Program databases for participants who underwent FIT between 2009 and 2010. We compared positivity rates, cancer detection rates, interval cancer rates, positive predictive value, sensitivity, and specificity for FIT during the spring, summer, fall, and winter seasons in Korea. In total, 4,788,104 FIT results were analyzed. FIT positivity rate was lowest during the summer months. In the summer, the positive predictive value of FIT was about 1.1 times (adjusted odds ratio (aOR) 1.08, 95% confidence interval (CI) 1.00-1.16) higher in the overall FIT group and about 1.3 times (aOR 1.29, 95% CI 1.10-1.50) higher in the quantitative FIT group, compared to those in the other seasons. Cancer detection rates, however, were similar regardless of season. Interval cancer risk was significantly higher in the summer for both the overall FIT group (aOR 1.16, 95% CI 1.07-1.27) and the quantitative FIT group (aOR 1.31, 95% CI 1.12-1.52). In addition, interval cancers in the rectum and distal colon were more frequently detected in the summer and autumn than in the winter. The positivity rate of FIT was lower in the summer, and the performance of the FIT screening program was influenced by seasonal variations in Korea. These results suggest that more efforts to reduce interval cancer during the summer are needed in population-based screening programs using FIT, particularly in countries with high ambient temperatures.

Role of Quantitative Fecal Immunochemical Test in Assessment of Mucosal Healing in Patients with Ulcerative Colitis

AbstractBackground: Ulcerative Colitis (UC) is a chronic inflam-matory disorder of the colorectum that is characterized by a remission and relapse course. Mucosal healing has been considered the goal of treatment in UC because it reduces the risk of relapse and colectomy. Fecal biomarkers have emerged as an important easy, rapid and non-invasive tool for assessing and monitoring mucosal healing in patients with UC.Aim of the Study: To determine if the q-FIT can evaluate the mucosal healing in UC patients.Patients and Methods: The study was conducted on 60 UC patients who underwent colonoscopy in the Endoscopy Unit, Internal Medicine Department in Tanta University Hospital. FIT was examined in stool samples from all the patients. Mucosal status was assessed using the Mayo Endo-scopic Subscore (MES).Data were collected from all study patients including; clinical, demographic and laboratory data. Statistical analysis was carried out for all collected data and statistical significance was determined at a p-value <0.05.Results: A total of 60 UC patients were evaluated with FIT results in conjunction with colonoscopies. The sensitivity and specificity of the FIT values (<100ng/ml) for predicting MH (MES 0 alone) were 0.93 and 0.80, respectively. The sensitivity and specificity when MH was defined as (MES 0 or 1) were 0.75 and 0.91, respectively. A significant correlations between FIT levels and the MES was observed (r=0.858, p-value=0.001 *).Conclusion: Quantitative FIT can be a non-invasive and effectivebiomarker for evaluation of mucosal healing in UC.

The importance of comparing quantitative faecal immunochemical tests (FIT) before selecting one for a population-based colorectal cancer screening programme

FIT for haemoglobin are now commonly used in many countries as the best, currently available, non-invasive test for colorectal cancer (CRC) in asymptomatic population screening programmes (1). FIT are available in two formats, qualitative, usually based on lateral-flow immunochromatographic test strips or cassettes, and quantitative, most often based on immunoturbidimetry, and performed on small benchtop analyzers. Quantitative FIT have a number of significant advantages over qualitative FIT, a major one being that analyses of faecal samples give estimates of the faecal haemoglobin concentrations (f-Hb) (2).

Quality Metrics of a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program in Korea.

Background/AimsKnowledge regarding the quality metrics of fecal immunochemical test (FIT)-based colorectal cancer screening programs is limited. The aim of this study was to investigate the performance and quality metrics of a FIT-based screening program.MethodsIn our screening program, asymptomatic subjects aged ≥50 years underwent an annual FIT, and subjects with positive FIT results underwent a subsequent colonoscopy. The performance of the FIT and colonoscopy was analyzed in individuals with a positive FIT who completed the program between 2009 and 2015 at a university hospital.ResultsAmong the 51,439 screened participants, 75.1% completed the FIT. The positive rate was 1.1%, and the colonoscopy completion rate in these patients was 68.6%. The positive predictive values of cancer and advanced neoplasia were 5.5% and 19.1%, respectively. The adenoma detection rate in the patients who underwent colonoscopy after a positive FIT was 48.2% (60.0% for men and 33.6% for women). The group with the highest tertile quantitative FIT level showed a significantly higher detection rate of advanced neoplasia than the group with the lowest tertile (odds ratio, 2.6; 95% confidence interval, 1.4 to 5.1; p<0.001).ConclusionsThe quality metrics used in the United States and Europe may be directly introduced to other countries, including Korea. However, the optimal quality metrics should be established in each country.

Faecal immunochemical tests (FIT) can help to rule out colorectal cancer in patients presenting in primary care with lower abdominal symptoms: a systematic review conducted to inform new NICE DG30 diagnostic guidance

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 42016037723

Direct Comparison of Diagnostic Performance of 9 Quantitative Fecal Immunochemical Tests for Colorectal Cancer Screening

A variety of fecal immunochemical tests (FITs) for hemoglobin (Hb) are used in colorectal cancer screening. It is unclear to what extent differences in reported sensitivities and specificities reflect true heterogeneity in test performance or differences in study populations or varying pre-analytical conditions. We directly compared the sensitivity and specificity values with which 9 quantitative (laboratory-based and point-of-care) FITs detected advanced neoplasms (AN) in a single colorectal cancer screening study. Pre-colonoscopy stool samples were obtained from participants of screening colonoscopy in Germany from 2005 through 2010 and frozen at -80°C until analysis. The stool samples were thawed, homogenized, and used for 9 different quantitative FITs in parallel. Colonoscopy and histology reports were collected from all participants and evaluated by 2 independent, trained research assistants who were blinded to the test results. Comparative evaluations of diagnostic performance for AN were made at preset manufacturers' thresholds (range, 2.0-17.0 μg Hb/g feces), at a uniform threshold (15 μg Hb/g feces), and at adjusted thresholds yielding defined levels of specificity (99%, 97%, and 93%). Of the 1667 participants who fulfilled the inclusion criteria, all cases with AN (n = 216) and 300 randomly selected individuals without AN were included in the analysis. Sensitivities and specificities for AN varied widely when we used the preset thresholds (21.8%-46.3% and 85.7%-97.7%, respectively) or the uniform threshold (16.2%-34.3% and 94.0%-98.0%, respectively). Adjusting thresholds to yield a specificity of 99%, 97%, or 93% resulted in almost equal sensitivities for detection of AN (14.4%-18.5%, 21.3%-23.6%, and 30.1%-35.2%, respectively) and almost equal positivity rates (2.8%-3.4%, 5.8%-6.1%, and 10.1%-10.9%, respectively). Apparent heterogeneity in diagnostic performance of quantitative FITs can be overcome to a large extent by adjusting thresholds to yield defined levels of specificity or positivity rates. Rather than simply using thresholds recommended by the manufacturer, screening programs should choose thresholds based on intended levels of specificity and manageable positivity rates.

Selecting a Cut-off for Colorectal Cancer Screening With a Fecal Immunochemical Test.

Objectives:Fecal immunochemical tests (FITs) for hemoglobin (Hb) are increasingly used for colorectal cancer (CRC) screening. However, cut-offs for defining test positivity are varying widely. We aimed to evaluate the impact of cut-off selection on key indicators of diagnostic performance in a true screening setting.Methods:We evaluated diagnostic performance of FOB Gold, a widely used quantitative FIT, for detecting advanced neoplasms (AN) across a wide range of possible cut-offs among 1822 participants of screening colonoscopy aged 50–79 years in Germany.Results:The positive predictive value (PPV) for detecting AN showed a very steep increase with increasing cut-off up to 35.2% (95% CI 29.9–40.9%) at a cut-off of 9 μg Hb/g feces at which sensitivity and specificity were 48.8% (95% CI 42.1–55.6%) and 88.5% (95% CI 86.8–89.9%), respectively. A further moderate increase of PPV up to 56.9% (95% CI 47.8–65.5%), along with a major decrease in sensitivity was observed when gradually increasing the cut-off to 25 μg Hb/g feces at which sensitivity and specificity were 31.9% (95% CI 25.9–38.5%) and 96.9% (95% CI 95.9–97.6%), respectively. Further increases of the cut-off hardly affected PPV and specificity, but went along with further relevant decline in sensitivity.Conclusions:Our study illustrates delineation of a range of meaningful cut-offs (here: 9–25 μg Hb/g feces) according to expected diagnostic yield in a true screening setting. Selecting a cut-off within or beyond this range should consider characteristics of the specific target population, such as AN prevalence or available colonoscopy capacity.

Impact of Fecal Hb Levels on Advanced Neoplasia Detection and the Diagnostic Miss Rate For Colorectal Cancer Screening in High-Risk vs. Average-Risk Subjects: a Multi-Center Study.

Objectives:The Asia-Pacific Colorectal Screening (APCS) scoring system was developed to identify high-risk subjects for advanced neoplasia. However, the appropriate fecal immunochemical test (FIT) cutoff for high-risk population may be different from that of average-risk population. We aimed to evaluate the FIT performance at different cutoffs in high-risk subjects undergoing colorectal cancer (CRC) screening.Methods:We prospectively enrolled asymptomatic subjects aged 50–75 years. Using the APCS score, subjects were stratified into either the average-risk or high-risk groups. All subjects were tested with one-time quantitative FIT and underwent colonoscopy. We compared the FIT performance for advanced neoplasia between two groups using different cutoffs (5 (FIT5), 10 (FIT10), 20 (FIT20), 30 (FIT30), and 40 (FIT40) μg Hb/g feces).Results:Overall, 1,713 subjects were recruited, and 1,222 (71.3%) and 491 (28.7%) were classified as average-risk and high-risk, respectively. Advanced neoplasia was detected in 90 (7.4%) of the average-risk subjects and 65 (13.2%) of the high-risk subjects. In the high-risk group, by decreasing the cutoff from FIT40 to FIT5, the sensitivity increased by 33.8 percentage points with decreased specificity by 11 percentage points. In the average-risk group, the sensitivity increased by 20 percentage points with decreased specificity by 9.6 percentage points. At the lowest cutoff (FIT5), the number of needed colonoscopies to find one advanced neoplasia was 2.8 and 6.1 for the high-risk and average-risk groups, respectively.Conclusions:Using an appropriate FIT cutoff for CRC screening in high-risk subjects could improve CRC screening performance and reduce the unnecessary colonoscopies. To maintain high sensitivity and specificity for advanced neoplasia, the optimal cutoff FIT in the high-risk subjects should be lower than that in the average-risk subjects.

Association Between Concentrations of Hemoglobin Determined by Fecal Immunochemical Tests and Long-term Development of Advanced Colorectal Neoplasia

Colorectal cancer (CRC) screening using quantitative fecal immunochemical tests (FITs) is rapidly gaining ground worldwide. FITs are invariably used in a dichotomous manner using pre-specified cut-off values. To optimize FIT-based screening programs, we investigated the association between fecal hemoglobin (fHb) concentrations below the FIT cut-off valueand later development of colorectal advanced neoplasia (AN). We analyzed data collected from a population-based study of 9561 average-risk subjects (50-74 years old) in the Netherlands who were offered 4 rounds of FIT screening for CRC from November 2006 through December 2014. We analyzed data from 7663 participants screened at least once and found to have a negative FIT result at baseline (below the cut-off value of 10 μg Hb/ g feces). Participants were followed for a median of 4.7 years (interquartile range, 2.0-6.1 years); CRCs diagnosed outside thescreening program were identified from the Dutch Comprehensive Cancer Centre database. Hazard ratios for AN were determined using Cox proportional hazard regression analyses. Logistic regression techniques were used to calculate risks of ANafter consecutive fHb concentrations below the cut-off value. After 8 years of follow-up, participants with baseline concentrations of 8-10 μg fHb/g had a higher cumulative incidence of AN (33%) than participants with 0 μg fHb/g (5%) (P< .001). Multi-variate hazard ratios increased from 1.2 for subjects with concentrations of 0-2 μg fHb/g to 8.2 for subjects with concentrations of 8-10 μg fHb/g (P < .001). Participantswith 2 consecutive fHb concentrations of 8 μg Hb/g had a 14-fold increase in risk of AN compared with participantswith 2 consecutive fHb concentrations of 0 μg Hb/g (P < .001). In a population-based study of average-risk individuals with a FIT result below the cut-off value, we associated baseline concentrations of 8-10 μg fHb/g with an increased risk of AN compared with baseline concentrations of 0 μg fHb/g. Baseline and consecutive fHb concentrations are independent predictors for incident AN. This information might be used in designing personalized strategies for population-based CRC screening and reduce unnecessary repeat tests. Trialregister.nl no: first round, NTR1096; second round and additional invitees, NTR1512.

Stool Based Testing for Colorectal Cancer: an Overview of Available Evidence.

The goal of this review is to summarize stool-based testing for colorectal cancer (CRC). The key questions answered in this review were the advantages and limitations of each available stool-based test for CRC and to examine their comparative efficacy. Guaiac-based fecal occult blood testing (gFOBT) is no longer a relevant test for CRC screening. fecal immunochemical testing (FIT) tests, especially quantitative assays, are clearly a reliable stool-based test. Multitarget DNA (mtsDNA) stool testing may represent a viable option as well, although cost and test characteristics are yet fully defined. FIT and mtsDNA represent the options for stool-based CRC screening. In larger screening centers, quantitative FIT assays represent an attractive option for stool-based testing. Qualitative FIT has applicability in smaller centers. Although a large validation trial showed promising results for mtsDNA, further head-to-head trials with FIT will help define the ultimate role of mtsDNA. Ultimately, however, the best test for CRC screening is the one performed stool-based CRC screening as an initial or alternative option can increase participation in CRC screening.