Clinical Features of Fecal Immunochemical Test-Negative Colorectal Lesions based on Colorectal Cancer Screening among Asymptomatic Participants in Their 50s

Objective: To improve the efficacy of colorectal cancer (CRC) screening, decreasing the occurrence of interval cancers is essential. Most interval CRCs develop from fecal immunochemical test (FIT)-negative CRC. This study examined the clinical characteristics of FIT-negative advanced neoplasms (AN) and sessile serrated lesions (SSL), which are main candidate precursors of FIT-negative CRC, and the eligibility criteria for total colonoscopy (TCS) screening following negative FIT. Methods: Asymptomatic participants in their 50s were divided into two groups. The FIT-negative group underwent TCS following negative FIT, and the TCS-only group underwent TCS without FIT. One endoscopist reviewed the endoscopic images. Plausible risk factors for colorectal polyps were extracted. The clinical features of AN and SSL were compared between the groups. Result: Of 2,437 participants, 56.2% were included in the FIT-negative group. No between-group differences were recorded for the prevalence of different colorectal polyp types. By multivariate analysis, a significantly lower adjusted odds ratio (AOR) of AN was shown in women, and significantly higher AORs of AN were found for aging, smoking, and a family history of CRC. The AOR of SSL was higher for smokers. The proportion of AN in the right colon was higher in the FIT-negative group. No between-group differences were recorded for SSL. Conclusion: FIT screening was less likely to detect CRC and certain precancerous lesions in the right colon. Combining annual FIT with TCS for the high-risk population based on a scoring system, may detect FIT-negative CRC and colorectal polyps, thus, reducing interval cancer.     

Comparative yield and efficiency of strategies based on risk assessment and fecal immunochemical test in colorectal cancer screening: A cross-sectional population-based analysis

ObjectiveIntegration of risk stratification into fecal immunochemical test (FIT) might aid in the suboptimal detection of advanced neoplasms by FIT in colorectal cancer (CRC) screening. A comparative study was conducted to evaluate the participation and diagnostic yield of the parallel combination of questionnaire-based risk assessment (QRA) and FIT, FIT-only and QRA-only strategies in a CRC screening program in China.MethodsThe study included 29,626 individuals aged 40−74 years and invited to participate in a CRC screening program in China. Participants were first invited to undertake QRA and one-time FIT (OC-sensor). Participants with positive QRA or FIT were deemed to be high-risk individuals who were recommended for subsequent colonoscopy. Participation, detection rate, and resource demand for colonoscopy were calculated and compared.ResultsOf the 29,626 invitees, 20,203 completed the parallel combination, 8,592 completed the QRA-only, and 11 completed the FIT-only strategy. For the parallel combination, FIT-only, and QRA-only strategies, the overall positivity rates were 10.2% (2,928/28,806), 5.4% (1,096/20,214), and 6.8% (1,944/28,795), respectively; the yield of advanced neoplasm per 10,000 invitees were 46.9 [95% confidence interval (95% CI): 39.8−55.4], 36.8 (95% CI: 30.5−44.4), and 12.2 (95% CI: 8.8−16.8), respectively; the positive predictive values for detecting advanced neoplasms among participants who completed colonoscopy were 4.7% (95% CI: 4.0%−5.6%), 9.9% (95% CI: 8.3%−11.9%), and 1.9% (95% CI: 1.3%−2.6%), respectively; the number of colonoscopies required to detect one advanced neoplasm was 11.4 (95% CI: 9.8−13.4), 5.7 (95% CI: 4.8−6.7), and 28.4 (95% CI: 20.7−39.2), respectively.ConclusionsThe parallel combination of QRA and FIT did not show superior efficacy for detecting advanced neoplasm compared with FIT alone in this CRC screening program.     

Impact of time between faecal immunochemical tests in colorectal cancer screening on screening results: A natural experiment

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT₂), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT₁), and time between the two screening rounds. 18 522 individuals with negative FIT₁ who attended FIT₂ were included in this study. 245 AN were detected at FIT₂, of which 34 were CRC. The CRC detection rate at FIT₂ for participants with FIT₁ = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT₁ ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT₁-value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT₁ ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.     

Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas

Given the current increase in colorectal cancer screening, information on performance of screening tests is needed, especially in groups with a presumed lower test performance. We compared test performance of immunologic fecal occult blood testing (FIT) and pseudosigmoidoscopy with colonoscopy for detection of advanced adenomas in an average risk screening population. In addition, we explored the influence of gender, age, and location on test performance. FIT was collected prior to colonoscopy with a 50 ng/mL cutoff point. FIT results and complete colonoscopy findings were available from 329 subjects (mean age: 54.6 ± 3.7 years, 58.4% women). Advanced adenomas were detected in 38 (11.6%) of 329 subjects. Sensitivity for advanced adenomas of FIT and sigmoidoscopy were 15.8% (95% CI: 6.0-31.3) and 73.7% (95% CI: 56.9-86.6), respectively. No sensitivity improvement was obtained using the combination of sigmoidoscopy and FIT. Mean fecal hemoglobin in FIT positives was significantly lower for participants with only proximal adenomas versus those with distal ones (P = 0.008), for women versus men (P = 0.023), and for younger (<55 years) versus older (≥55 years) subjects (P = 0.029). Sensitivities of FIT were 0.0% (95% CI: 0.0-30.9) in subjects with only proximal versus 21.4% (95% CI: 8.3-41.0) in those with distal nonadvanced adenomas; 5.3% (95% CI: 0.0-26.0) in women versus 26.3% (95% CI: 9.2-51.2) in men; 9.5% (95% CI: 1.2-30.4) in younger versus 23.5% (95% CI: 6.8-49.9) in older subjects. Sigmoidoscopy had a significantly higher sensitivity for advanced adenomas than FIT. A single FIT showed very low sensitivity, especially in subjects with only proximal nonadvanced adenomas, in women, and in younger subjects. This points to the existence of "low" FIT performance in subgroups and the need for more tailored screening strategies.     

Lack of Association between Red Meat Consumption and a Positive Fecal Immunochemical Colorectal Cancer Screening Test in Khon Kaen,Thailand: a Population- Based Randomized Controlled Trial

Background: There is convincing evidence from epidemiological studies that meat consumption increases colorectal cancer (CRC) risk. However, assessment of any association with a positive fecal immunochemical test (FIT) in CRC screening has been limited. If a link could be shown this might be helpful for establishing a risk group for colonoscopy. Objective: This study aimed to assess any association between meat consumption and other lifestyle factors and a positive FIT result in a Thai population. Methods: A cross-sectional analytical study was conducted with 1,167 participants in a population-based randomized controlled trial. CRC was screened from May 2016 - February 2017. Subjects aged 45-74 years who met the eligibility criteria were randomly allocated to the study arm. A positive FIT was determined with cut-off 100 ng/mL. Multiple logistic regression was used to analyze any relationship between lifestyle factors and a positive FIT. Result: The total number of subjects was 1,060 (90.8% return rate of FIT). With FIT100, FIT150, and FIT200, positive tests were found in 92 (8.68%), 74 (6.98%), and 60 (5.66%), respectively. No significant associations were noted with any of the variables, except for being aged 60-74 years (ORadj = 1.62, 95% CI: 1.03-2.54) Borderline significance was observed for high consumption of vegetables (ORadj = 0.62, 95% CI: 0.36-1.07) and being male (ORadj = 1.39, 95% CI: 0.87-2.22). Conclusion: Despite the evidence from the literature, no association was here found between a positive FIT result and meat consumption or other well-established lifestyle parameters. Being aged 60-74 years was a risk factor which should be taken into account in CRC screening strategy in countries like Thailand with limited access to endoscopy.     

Factors associated with interval colorectal cancer after negative FIT: Results of two screening rounds in the Dutch FIT-based CRC screening program

The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT-based CRC screening program in the Netherlands, using data from individuals who participated in FIT-screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT-negative participants (<47 μg Hb/g feces [μg/g]), FIT-sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f-Hb). FIT-sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f-Hb affects probability of detecting interval CRC, adjusted for sex- and age-differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT-sensitivity based on the detection method was 84.4% (95%CI 83.8-85.0) in the first and 73.5% (95% CI 71.8-75.2) in the second screening round. The proportional incidence method resulted in a FIT-sensitivity of 76.4% (95%CI 73.3-79.6) in the first and 79.1% (95%CI 73.7-85.3) in the second screening round. After one negative FIT, participants with f-Hb just below the cut-off (>40-46.9 μg/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0-20.4) than had participants with unmeasurable f-Hb (0-2.6 μg/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8-17.6) for participants with f-Hb just below the cut-off compared with participants with unmeasurable f-Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT-sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk-stratified CRC screening based on prior f-Hb.     

A new insight into fecal hemoglobin concentration‐dependent predictor for colorectal neoplasia

We sought to assess how much of the variation in incidence of colorectal neoplasia is explained by baseline fecal hemoglobin concentration (FHbC) and also to assess the additional predictive value of conventional risk factors. We enrolled subjects aged 40 years and over who attended screening for colorectal cancer with the fecal immunochemical test (FIT) in Keelung community‐based integrated screening program. The accelerated failure time model was used to train the clinical weights of covariates in the prediction model. Datasets from two external communities were used for external validation. The area under curve (AUC) for the model containing only FHbC was 83.0% (95% CI: 81.5–84.4%), which was considerably greater than the one containing only conventional risk factors (65.8%, 95% CI: 64.2–67.4%). Adding conventional risk factors did not make significant additional contribution (p = 0.62, AUC = 83.5%, 95% CI: 82.1–84.9%) to the predictive model with FHbC only. Males showed a stronger linear dose‐response relationship than females, yielding gender‐specific FHbC predictive models. External validation confirms these results. The high predictive ability supported by a dose‐dependent relationship between baseline FHbC and the risk of developing colorectal neoplasia suggests that FHbC may be useful for identifying cases requiring closer postdiagnosis clinical surveillance as well as being an early indicator of colorectal neoplasia risk in the general population. Our findings may also make contribution to the development of the FHbC‐guided screening policy but its pros and cons in connection with cost and effectiveness of screening should be evaluated before it can be applied to population‐based screening for colorectal cancer.     

Plasma miRNA-based signatures in CRC screening programs

Colorectal cancer (CRC) screening programs help diagnose cancer precursors and early cancers and help reduce CRC mortality. However, currently recommended tests, the fecal immunochemical test (FIT) and colonoscopy, have low uptake. There is therefore a pressing need for screening strategies that are minimally invasive and consequently more acceptable to patients, most likely blood based, to increase early CRC identification. MicroRNAs (miRNAs) released from cancer cells are detectable in plasma in a remarkably stable form, making them ideal cancer biomarkers. Using plasma samples from FIT-positive (FIT+) subjects in an Italian CRC screening program, we aimed to identify plasma circulating miRNAs that detect early CRC. miRNAs were initially investigated by quantitative real-time PCR in plasma from 60 FIT+ subjects undergoing colonoscopy at Fondazione IRCCS Istituto Nazionale dei Tumori, then tested on an internal validation cohort (IVC, 201 cases) and finally in a large multicenter prospective series (external validation cohort [EVC], 1121 cases). For each endoscopic lesion (low-grade adenoma [LgA], high-grade adenoma [HgA], cancer lesion [CL]), specific signatures were identified in the IVC and confirmed on the EVC. A two-miRNA-based signature for CL and six-miRNA signatures for LgA and HgA were selected. In a multivariate analysis including sex and age at blood collection, the areas under the receiver operating characteristic curve (95% confidence interval) of the signatures were 0.644 (0.607–0.682), 0.670 (0.626–0.714) and 0.682 (0.580–0.785) for LgA, HgA and CL, respectively. A miRNA-based test could be introduced into the FIT+ workflow of CRC screening programs so as to schedule colonoscopies only for subjects likely to benefit most.     

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information-system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut-off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut-off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non-participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut-off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut-off were detected in the subsequent round.     

Uptake of faecal immunochemical test screening among nonparticipants in a flexible sigmoidoscopy screening programme

Screening programmes based on single modality testing may prevent individuals with a preference for a different test from participating. We conducted a population-based trial to determine whether nonparticipants in flexible sigmoidoscopy (FS) screening were willing to attend faecal immunochemical test (FIT) screening. In total, 8,407 subjects were invited in a primary FS screening programme. Invitees did not know at the time of FS invitation that nonparticipants would be offered FIT screening. A total of 4,407 nonparticipants of FS screening were invited for FIT screening (cut-off 50 ng haemoglobin/ml). The participation rate to FS screening was 31% [95% confidence interval (CI): 30-32%]. Among the FS nonparticipants 25% (CI: 24-26%) did attended FIT screening. The participation rate of the two-stage recruitment for FS and FIT screening was 45% (CI: 44-46%). FIT screenees were older (p = 0.02), more often women (p < 0.001) and had a lower social economic status (p = 0.01) than FS screenees. The detection rate (DR) for advanced adenoma was 3.5% (CI: 2.5-4.8%), and for colorectal cancer (CRC) it was 0.3% (CI: 0.1-0.8%) among participants to FIT screening. The DR of the two-stage recruitment was 6.1% (n = 202) for an advanced adenoma and 0.5% (n = 16) for a CRC. In conclusion, offering FIT screening to nonparticipants in a FS screening programme increases the overall participation rate considerably, as a quarter of nonparticipants of FS screening was willing to attend FIT screening. The participation rate remains lower for primary FIT screening in the same population (62%). Women in the target population were more likely to refuse FS than FIT screening. Countries introducing FS screening should be aware of these preferences.     

Predictors of colorectal cancer screening from patients enrolled in a managed care health plan

BACKGROUND: Despite the growing recognition of the importance of colorectal cancer (CRC) screening in reducing cancer mortality, national screening rates are low, indicating a critical need to understand the barriers and remedies for underutilization of CRC screening tests. METHODS: Using results from independent cross-sectional telephone surveys with patients aged>or=50 years performed before (2000; n=498) and after (2003; n=482) a quality improvement intervention for CRC screening within a large managed care health plan, the trends and predictors of CRC screening with fecal occult blood test (FOBT) and/or endoscopy (flexible sigmoidoscopy/colonoscopy) were examined from a patient perspective. RESULTS: In 2000, patient reported screening rates within guidelines were 38% for any test, 23% for endoscopy, and 22% for FOBT. In 2003, screening rates increased to 50% for any test, 39% for endoscopy, and 24% for FOBT. Having discussed CRC with a doctor significantly increased the odds of being screened (FOBT: odds ratio [OR], 2.09 [95% confidence interval (95% CI), 1.47-2.96]; endoscopy: OR, 2.33 [95% CI, 1.67-3.26]; and any test: OR, 2.86 [95% CI, 2.06-3.96]), and reporting barriers to CRC in general decreased the odds of being screened (FOBT: OR, 0.76 [95% CI, 0.60-0.95]; endoscopy: OR, 0.74 [95% CI, 0.60-0.92]; and any test: OR, 0.66 [95% CI, 0.54-0.80]). CONCLUSIONS: Although screening rates increased over the 3-year period, evidence was found of ongoing underutilization of CRC screening. The 2 strongest determinants of obtaining CRC screening were provider influence and patient barriers related to CRC screening in general, pointing to the need for multilevel interventions that target both the provider and patient.     

Current noninvasive tests for colorectal cancer screening: An overview of colorectal cancer screening tests

Colorectal cancer (CRC) has become the third most common cancer in the world. Screening has been shown to be an effective way to identify early CRC and precancerous lesions, and to reduce its morbidity and mortality. Several types of noninvasive tests have been developed for CRC screening, including the fecal occult blood test (FOBT), the fecal immunochemical test (FIT), the fecal-based DNA test and the blood-based DNA test (the SEPT9 assay). FIT has replaced FOBT and become the major screening test due to high sensitivity, specificity and low costs. The fecal DNA test exhibited higher sensitivity than FIT but its current cost is high for a screening assay. The SEPT9 assay showed good compliance while its performance in screening needs further improvements. These tests exhibited distinct sensitivity and specificity in screening for CRC and adenoma. This article will focus on the performance of the current noninvasive in vitro diagnostic tests that have been used for CRC screening. The merits and drawbacks for these screening methods will also be compared regarding the techniques, usage and costs. We hope this review can provide suggestions for both the public and clinicians in choosing the appropriate method for CRC screening.     

Diagnostic value of fecal tumor M2-pyruvate kinase for CRC screening: a systematic review and meta-analysis

The measurement of fecal tumor M2-pyruvate kinase (PKM2), overexpressed in tumor cells, has been proposed as a novel tool for detecting colorectal cancer (CRC). However, the sensitivity and specificity of this test varied among studies. The aim of this meta-analysis was to determine the diagnostic accuracy of fecal PKM2 for CRC and to evaluate its utility in the CRC screening. It was compared to guaiac fecal occult blood test (gFOBT) or immunological fecal occult blood test (iFOBT). Through comprehensive literature search, 10 studies met the inclusion criteria and were included. Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The hierarchical summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of fecal PKM2 for detecting CRC were 79% (95% CI = 75-83%) and 81% (95% CI = 73-87%), respectively. The summary positive predictive value and negative predictive value were 74% (95% CI = 56-87%) and 86% (95% CI = 79-91%), respectively. The pooled diagnostic odds ratio was 16 (95% CI = 10-26). In head-to-head comparison, the diagnostic odds ratio of PKM2 and gFOBT for CRC were 10.167 (95% CI = 5.992-17.250) and 6.557 (95% CI = 3.467-12.403), respectively. The diagnostic odds ratio of PKM2 and iFOBT for CRC were 9.542 (95% CI = 5.893-15.452) and 67.248 (95% CI = 16.194-279.26), respectively. The fecal PKM2 test was a diagnostic tool with moderate sensitivity and specificity for detecting CRC. Its diagnostic efficiency was similar to that of gFOBT. Because of its relatively low specificity and positive predict value, fecal PKM2 was not recommended used alone as a screening tool for CRC.     

Changes in colorectal cancer screening use after introduction of alternative screening offer in Germany: Prospective cohort study

In October 2002, screening colonoscopy was added to the German colorectal cancer (CRC) screening program as an alternative to fecal occult blood test (FOBT). We aimed to evaluate the change in CRC screening use after introduction of the dual screening offer and to assess determinants of screening use. Data were drawn from a population-based cohort study initiated during 2000–2002 in Germany (n = 5,845, age range at recruitment: 50–75 years). We conducted both cross-sectional and longitudinal analyses to obtain uptake rates of CRC screening based on four waves of data. Age-group specific proportions of participants having had FOBT within 2 years remained essentially unchanged at 61–67% between 2000 and 2002 (1st wave) and 2005–2007 (3rd wave). The proportions of participants having undergone screening colonoscopy within 10 years increased from 23–29% to 46–57%, leading to a substantial overall increase in being up-to-date with CRC screening from 66–68% to 77–80%. In 2008–2010 (4th wave), FOBT use declined and colonoscopy use continued to increase. Obesity was significantly associated with lower prevalence of being up-to-date with FOBT (odds ratio [OR] at 8-year follow-up 0.68; 95% confidence interval [CI], 0.58–0.80) and screening colonoscopy (OR, 0.73; 95% CI, 0.62–0.86). Also, smokers were less likely to have ever used FOBT (OR, 0.54; 95% CI, 0.40–0.75) or colonoscopy (OR, 0.75; 95% CI, 0.63–0.90) compared to nonsmokers. After the introduction of dual screening offer, the overall adherence to CRC screening steeply increased, mainly due to an increase in screening colonoscopy uptake. Screening tests kept being underused by obese people and smokers who are at elevated CRC risk.     

A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test,despite lower compliance rate. A prospective,controlled, feasibility study

Immunochemical fecal occult blood test (FIT) is a new colorectal cancer (CRC) screening method already recommended by the American screening guidelines. We aimed to test the feasibility of FIT as compared to guaiac fecal occult blood test (G‐FOBT) in a large urban population of Tel Aviv. Average‐risk persons, aged 50–75 years, were offered FIT or G‐FOBT after randomization according to the socioeconomic status of their clinics. Participants with positive tests underwent colonoscopy. Participants were followed through the Cancer Registry 2 years after the study. Hemoccult SENSA? and OC‐MICRO? (three samples, 70 ng/ml threshold) were used. FIT was offered to 4,657 persons (Group A) and G‐FOBT to 7,880 persons (Group B). Participation rate was 25.9% and 28.8% in Group A and B, respectively (p < 0.001). Positivity rate in Group A and B was 12.7% and 3.9%, respectively (p < 0.001). Cancer found in six (0.49%) and eight (0.35%) patients of Group A and B, respectively (NS). Cancer registry follow‐up found missed cancer in five (0.22%) cases of Group B and none in Group A (NS). The sensitivity, specificity, negative and positive predictive value for cancer in Group A and B were 100%, 85.9%, 100%, 3.9% and 61.5%, 96.4%, 99.8%, 9.1%, respectively. There was increased detection of advanced adenomatous polyp (AAP) by FIT, irrespective of age, gender, and socioeconomic status (Per Protocol: odds ratio 2.69, 95% confidence interval 1.6–4.5; Intention to Screen: odds ratio 3.16, 95% confidence interval 1.8–5.4). FIT is feasible in urban, average‐risk population, which significantly improved performance for detection of AAP and CRC, despite reduced participation.     

Factors associated with false-positive fecal immunochemical tests in a large German colorectal cancer screening study

In recent years fecal immunochemical tests (FITs) have been offered as a primary screening test for colorectal cancer (CRC) in a growing number of countries. Our study aims to identify factors associated with apparently false-positive results of FITs. In this cross-sectional study within the German population-based screening colonoscopy program, participants were invited to provide a stool sample for FIT prior to colonoscopy. Four thousand six hundred and fifty six participants aged 50–79 years with no known history of CRC or inflammatory bowel disease (IBD) and no findings of neoplasms at screening colonoscopy were included in the current analyses. Main outcome measures were rates and factors associated with apparently false-positive FIT results. Apparently false-positive FIT results were found for 378 participants (8.1%). Male sex (OR = 1.30, 95%CI 1.03, 1.62), age ≥65 years (OR = 1.27, 95%CI 1.01, 1.59), a BMI ≥30 kg/m² (OR = 1.81, 95%CI 1.36, 2.40), current smoking (OR = 1.63, 95%CI 1.18, 2.25), use of aspirin (OR = 1.36, 95%CI 1.02, 1.82) and a new diagnosis of IBD (OR = 9.13, 95%CI 2.18, 38.19) or other non-neoplastic findings (OR = 1.86, 95%CI 1.37, 2.51) at screening colonoscopy were independently associated with significantly increased odds of a positive FIT. Although considered false positive in the context of CRC screening, the identified factors associated with apparently false-positive FIT results are known risk factors for and may point to conditions other than colorectal neoplasms that may be potential sources of gastrointestinal bleeding, potentially requiring further medical follow up.     

Cumulative evaluation of a quantitative immunochemical fecal occult blood test to determine its optimal clinical use

BACKGROUND:

Quantified, human hemoglobin (Hb)‐specific, immunochemical fecal occult blood test (IFOBT) measurements are now used for colorectal cancer (CRC) screening. The objective was to evaluate sensitivity and specificity for CRC and advanced adenomatous polyps (APs) by the fecal Hb threshold used to determine a positive test and the number of IFOBTs prepared per test, so as to determine the least number of colonoscopies required to detect a neoplasm.

METHODS:

Cumulative data were analyzed from a prospective cross‐sectional double‐blind study of 1682 consecutive, ambulatory, nonbleeding colonoscopy patients who volunteered for IFOBTs, most of above average risk, from 3 ambulatory‐endoscopy centers. Fecal Hb was measured in 3 samples and analyzed by an automated instrument, and the highest result ≥50 ng Hb/mL of buffer was related to findings.

RESULTS:

Colonoscopy identified CRC in 20 patients and advanced APs in 129. Sensitivity for either was best when any of 3 tests had ≥50 ng Hb/mL of buffer; sensitivity was 61.1% (95% confidence interval [CI], 53.2‐68.9), and specificity was 87.8% (95% CI, 86.2‐89.4). Positive tests identified 100% of CRCs and 55% of advanced APs every 3.1 colonoscopies. Sensitivity of a single test at the commonly used 100‐ng Hb/mL threshold was lower at 31.5% (95% CI, 24.1‐39.0) (P<.001), but specificity was higher at 96.4% (95% CI, 95.5‐97.3) (P<.001). Positive tests identified 65% of CRCs and 26.4% of advanced APs every 2.2 colonoscopies.

CONCLUSIONS:

The fecal Hb cutoff chosen by the screener and the number of samples collected per patient determine sensitivity and specificity for CRC/advanced AP; these factors determine the number of colonoscopies needed for positive tests and neoplasia yield. This information provides guidelines for IFOBT screening. Limitations are 1‐time screening and most examinees not being at average risk for CRC. Cancer 2010. © 2010 American Cancer Society.     

Making colonoscopy-based screening more efficient: A “gateopener” approach

Screening colonoscopy for early detection and prevention of colorectal cancer (CRC) is mostly used inefficiently. Here, we assessed the potential of an innovative approach to colonoscopy-based screening, by use of a single, low threshold fecal immunochemical test (FIT) as a “gateopener” for screening colonoscopy. Using COSIMO, a validated simulation model, we modeled scenarios including either direct invitation to screening colonoscopy or an alternative approach involving mailing a single (“gateopener”) FIT along with an invitation to colonoscopy contingent on a FIT value above a low threshold yielding a 50% positivity rate (ie, every other pretest will be positive). Under plausible assumptions on screening offer adherence, we found that such “gateopener screening” (use of screening colonoscopy contingent on a positive, low threshold gateopener FIT) approximately doubled cancer detection rates vs conventional screening. In those spared from screening colonoscopy due to a negative gateopener FIT pretest, numbers needed to screen were 10-times higher vs those for individuals with a positive FIT, peaking in >2000 and >3800 (hypothetically) needed colonoscopies to detect one case of cancer in men and women, respectively. Gateopener screening resulted in 42%-51% and 59%-65% more prevented CRC cases and deaths, respectively. In summary, by directing colonoscopy capacities to those most likely to benefit, offering screening colonoscopy contingent on a “gateopener” low-threshold FIT would substantially enhance efficiency of colonoscopy screening.     

Effect of oral anticoagulants on the outcome of faecal immunochemical test

Background:

We aimed to evaluate whether oral anticoagulants (OACs) alter faecal immunochemical test (FIT) performance in average-risk colorectal cancer (CRC) screening.

Methods:

Individuals aged 50–69 years were invited to receive one FIT sample (cutoff 75 ng ml^–1) between November 2008 and June 2011.

Results:

Faecal immunochemical test was positive in 9.3% (21 out of 224) of users of OAC and 6.2% (365 out of 5821) of non-users (P-trend=0.07). The positive predictive value (PPV) for advanced neoplasia (AN) in non-users was 50.4% vs 47.6% in users (odds ratio, 0.70; 95% CI, 0.3–1.8; P=0.5). The PPV for AN in OAC more antiplatelets (aspirin or clopidogrel) was 75% (odds ratio, 2; 95% CI, 0.4–10.8; P=0.4).

Conclusions:

Oral anticoagulant did not significantly modify the PPV for AN in this population-based colorectal screening program. The detection rate of advanced adenoma was higher in the combination OAC more antiplatelets.