Positive Fecal Immunochemical Test Result Research Articles

An Exploratory Analysis of Fecal Immunochemical Test Performance for Colorectal Cancer Screening in Nigeria.

The fecal immunochemical test (FIT) for hemoglobin is recommended for colorectal cancer (CRC) screening in resource-limited environments. However, there are several unique variables that may alter FIT performance in this setting, including endemic intestinal parasites and high ambient temperature. This prospective study evaluated the performance of FIT in asymptomatic, average-risk individuals of screening age in rural Nigeria. Three hundred and twenty-four community volunteers completed a questionnaire and provided stool specimens for parasitology and microbiome analysis. Specimens were frozen and stored at -80°C. Of 324 subjects, 139 met criteria for average-risk CRC screening and had a stool sample for analysis. These were thawed and tested with a qualitative FIT. Specimens positive for occult blood were retested every two days to evaluate the impact of time and temperature on test performance. Of 139 individuals, 69 (49.6%) were positive for intestinal parasites and 10 (7.2%) were positive for occult blood. The most common pathogen was Cryptosporidium (40.6%). Among patients with intestinal parasites, 10.1% (7/69) had a positive FIT. Only 4.3% (3/70) of patients without parasites had a positive FIT (p = 0.208). On bivariate analysis, sociodemographic variables were not associated with a positive FIT result. Thirty percent (3/10) of the FIT-positive specimens became FIT-negative with routine storage. Although a positive FIT result was more common in those with parasitic infection, the relationship was not significant in this small cohort. The impact of high ambient temperature on test positivity may necessitate shorter processing time guidelines for equatorial countries. Additional prospective studies are needed to validate FIT performance in Nigeria.

The Timing of a Diagnostic Colonoscopy After a Positive Fecal Immunochemical TestResult.

The Timing of a Diagnostic Colonoscopy After a Positive Fecal Immunochemical TestResult.

A Simple and Highly Specific MassARRAY-Based Stool DNA Assay to Prioritize Follow-up Decisions in Fecal Immunochemical Test-Positive Individuals.

Background: Seventy-five percent of fecal immunochemical test (FIT)-positive individuals are false positives and undergo unnecessary colonoscopies. Here, we established a stool DNA (sDNA) test that uses the Single Allele Base Extension Reaction (SABER) MassARRAY platform to improve the accuracy of FIT-based CRC detection. Methods: Twenty-one variants in five CRC-associated genes were selected for the sDNA panel. Cell line DNA and matched mutation-confirmed tissue and stool samples from 34 patients were used for accuracy assessment (cohort 1). The clinical performance of the sDNA assay was further evaluated in 101 independent FIT-positive stool samples (cohort 2). Results: In cohort 1, we obtained a 62% mutation concordance rate in paired tissue and stool samples of the CRC group, regardless of the FIT status. In cohort 2, 100% specificity in normal controls with positive FIT results was observed. By weighting the FIT value and the presence of a given variant type in stool and then summing the two scores, we found that a one-increment increase in the score was associated with a 4.538-fold risk (95% CI = 2.121–9.309) for malignancy in the FIT-positive setting. Conclusions: Our highly specific sDNA assay can help prioritize the most at-risk FIT-positive persons to receive prompt colonoscopic confirmation of CRC.

GPs' perspectives on colorectal cancer screening and their potential influence on FIT-positive patients: an exploratory qualitative study from a Dutch context.

BackgroundIn the Dutch colorectal cancer (CRC) screening programme, individuals receive a faecal immunochemical test (FIT) to do at home. After a positive FIT result, a follow-up colonoscopy is recommended to identify CRC or advanced adenomas (AA). GPs may influence their patients’ decisions on adherence to follow-up by colonoscopy.AimTo explore GPs’ perspectives on the CRC screening programme and their potential influence on FIT-positive patients to follow up with the recommended colonoscopy.Design & settingSemi-structured interviews among GPs in Amsterdam, the Netherlands.MethodGPs were approached using purposive sampling. Analysis was performed on 11 interviews using open coding and constant comparison.ResultsAll interviewed GPs would recommend FIT-positive patients without obvious contraindications to adhere to a follow-up colonoscopy. If patients were likely to be distressed by a positive FIT result, most GPs described using reassurance strategies emphasising a low cancer probability. Most GPs stressed the probability of false-positive FIT results. Some described taking a positive screening result in CRC screening less seriously than one in breast cancer screening. Most GPs underestimated CRC and AA probabilities after a positive FIT result. When told the actual probabilities, some stated that this knowledge might change the way they would inform patients.ConclusionThese results imply that some of the interviewed GPs have too low a perception of the risk associated with a positive FIT result, which might influence their patients’ decision-making. Simply informing GPs about the actual rates of CRC and AA found in the screening programme might improve this risk perception.

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

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

A National Bowel Cancer Screening Programme using FIT: Achievements and Challenges.

Colorectal cancer accounts for 11% of all cancer-related deaths in Ireland. With the aim of diagnosing these cancers at an earlier stage, and detecting premalignant lesions, the National Screening Service (NSS) offered a fecal immunochemical test (FIT) to all individuals aged 60 to 69. All individuals in the age range were contacted by post and invited to participate in the programme. Those with a positive FIT result were offered a colonoscopy in an internationally accredited unit. From an eligible population of 488,628, 196,238 individuals participated giving an uptake of 40.2%. Commencing at a FIT threshold of 20 μg Hg/g feces, the positivity rate was 8.6%, which overwhelmed colonoscopy capacity and, thus, the threshold was increased to 45 μg, resulting in an overall 5% positivity rate. A total of 520 individuals had cancer detected (68.3% stage I or II), of which 104 were removed endoscopically (pT1s). Adenomas were present in 54.2% of all colonoscopies, 17.4% deemed high risk. Despite a lower uptake, males were twice as likely to have colorectal cancers as females and had a 59% increased rate of high-risk adenomas diagnosed. Challenges facing the programme include increasing participation, especially among males, and increasing colonoscopy capacity. The ability to alter the sensitivity of FIT to match colonoscopy capacity is a valuable option for such a programme as it ensures that the maximum public health benefit can be achieved within available resources.

Yield of repeat colonoscopy in asymptomatic individuals with a positive fecal immunochemical test and recent colonoscopy

A fecal immunochemical test (FIT) is often repeated annually, even after a recent colonoscopy. However, there are no published data on the proper approach to FIT-positive patients after a recent colonoscopy. We compared colorectal cancer (CRC) and advanced colorectal neoplasia (ACRN) prevalence based on the interval since the last colonoscopy. We reviewed asymptomatic screenees aged≥50 years who underwent FIT and colonoscopy. Of 2228 FIT-positive participants, 514 had a colonoscopy less than 3 years before (group 1), 427 had a colonoscopy had a colonoscopy 3 to 10 years before (group 2), and 1287 had a colonoscopy >10 years before or no colonoscopy (group 3). The prevalence of CRC in groups 1, 2, and 3 was 2.1%, 1.6%, and 7.2%, respectively, and that for ACRN was 10.9%, 12.6%, and 26.0%, respectively. Even after adjusting for confounders, CRC and ACRN detection rates in group 1 were lower than those in group 3 but not lower than those in group 2. Among 6135 FIT-negative participants, the prevalence of CRC in the 3 groups was .7%, .4%, and 3.4%, respectively, and that for ACRN was 6.0%, 6.1%, and 14.7%, respectively. CRC and ACRN detection rates were significantly higher in FIT-positive participants than in FIT-negative participants in all 3 groups. In FIT-positive patients who underwent colonoscopy within the prior 3 years, CRC and ACRN prevalence was not low. Our findings support the U.S. Multi-Society Task Force on the CRC screening recommendation that repeat colonoscopy be offered to patients with positive FIT results and recent colonoscopy.

Association of time to colonoscopy after a positive fecal test result and fecal hemoglobin concentration with risk of advanced colorectal neoplasia

BackgroundWe evaluated the risk of advanced colorectal neoplasia (ACRN) and colorectal cancer (CRC) according to time to colonoscopy after positive fecal immunochemical test (FIT), fecal hemoglobin concentration, and combination of both. MethodsWe analyzed the records of 2362 patients aged ≥50 years who underwent colonoscopy because of a positive FIT result through the National Cancer Screening Program of Korea. ResultsACRN risk increased with increasing time to colonoscopy after a positive FIT (17.2%, 18.6%, 19.1%, 21.4%, and 27.2% in <30, 30–59, 60–149, 150–179, and ≥180 days; P = 0.034), and ACRN and CRC risk increased with increasing fecal hemoglobin concentration (ACRN, 13.2%, 16.9%, 18.5%, 23.2%, and 26.6%; CRC, 1.3%, 1.7%, 4.7%, 5.7%, and 12.8% with 100–200, 200–300, 300–500, 500–1000, and ≥1000 ng Hb/mL; both P < 0.001). Even after adjusting for confounders, follow-up after 180 days tended to be associated with a higher ACRN risk (adjusted odds ratio, 1.73; 95% confidence interval [CI], 0.91-3.27), compared with follow-up colonoscopy at <30 days, and fecal hemoglobin 500–1000, and ≥1000 ng Hb/mL were associated with a significantly higher ACRN and CRC risk, compared with 100–200 ng Hb/mL. Moreover, the group with ≥180 days and ≥1000 ng Hb/mL had a much higher CRC risk compared with the group with <180 days and <1000 ng Hb/mL (12.45-fold; 95% CI, 3.73–41.57). ConclusionsPatients with positive FIT results, especially those with higher fecal hemoglobin levels, should undergo timely follow-up colonoscopy.

Diagnostic yield and miss rate of EndoRings in an organized colorectal cancer screening program: the SMART (Study Methodology for ADR-Related Technology) trial

The EndoRings add-on has been claimed to improve adenoma detection at colonoscopy, but available data are inconsistent. When testing a new technology, parallel and crossover methodologies measure different outcomes, leaving uncertainty about their correspondence. The aims of this study were to compare the diagnostic yield and miss rate of the EndoRings for colorectal neoplasia. Consecutive patients undergoing colonoscopy after a positive fecal immunochemical test (FIT) within an organized screening program in 7 Italian centers were randomized between a parallel (EndoRings or standard) or a crossover (EndoRings/standard or standard/EndoRings) methodology. Outcomes measures were the adenoma detection rate (ADR) and advanced adenoma detection rate (AADR) in the parallel arms and the miss rate of adenomas in the crossover arms. Of 958 eligible patients, 927 (317 EndoRings; 317 standard; 142 EndoRings/standard; 151 standard/Endo-Rings) were included in the final analysis. In the parallel arms (mean ADR, 51.3%; mean AADR, 25.4%), no difference between standard and EndoRings was found for both ADR (relative risk [RR], 1.10; 95% confidence interval [CI], 0.95-1.28) and AADR (RR, 1.16; 95% CI, 0.88-1.51), as well as for the mean number of adenomas and advanced adenomas per patient (EndoRings, 1.9 ± 1.3 and 1.0 ± 1.2; standard, 2.1 ± 1.5 and 1.0 ± 1.2; P= not significant for both comparisons). In the crossover arms, no difference in the miss rate for adenomas between EndoRings and standard was found at per polyp (RR, 1.43; 95% CI, 0.97-2.10) or per-patient analysis (24% vs 26%; P= .76). No statistically significant difference in diagnostic yield and miss rate between EndoRings and standard colonoscopy was detected in patients with a positive FIT result. A clinically relevant correspondence between miss and detection rates was shown, supporting a cause-effect relationship. (ISRCTN registry: ISRCTN10357435.).

Delineating Deficiencies in Care Processes After Positive Fecal Immunochemical Test Results

Delineating Deficiencies in Care Processes After Positive Fecal Immunochemical Test Results

Barriers to Follow-up Colonoscopies for Patients With Positive Results From Fecal Immunochemical Tests During Colorectal Cancer Screening

Colorectal cancer is common yet largely preventable. The fecal immunochemical test (FIT) is a highly recommended screening method, but patients with positive results must receive a follow-up colonoscopy to determine if they have precancerous or cancerous lesions. We characterized colonoscopic follow-up evaluations and reasons for lack of follow-up in a Veterans Affairs (VA) cohort. We conducted a retrospective cross-sectional analysis of patients 50 to 75 years old with a positive FIT result from January 1, 2014, through May 31, 2016, in a network of 12 VAs sites in southern California. We determined the proportion of patients who received a follow-up colonoscopy, median time to colonoscopy, and colonoscopy findings. For patients who did not undergo colonoscopy, we determined the documented reason for lack of colonoscopy and factors associated with declining the colonoscopy examination. Of the 10,635 FITs performed, 916 (8.6%) produced positive results; 569 of these (62.1%) were followed by colonoscopy. The median time to colonoscopy after a positive FIT result was 83 days (interquartile range, 54-145 d), which did not vary between veterans who received a colonoscopy at a VA facility (81 d; interquartile range, 52-143 d) vs a non-VA site (87 d; interquartile range, 60-154 d) (P= .2). For the 347 veterans (37.9%) who did not undergo follow-up colonoscopy, the reasons were patient-related (49.3%), provider-related (16.4%), system-related (12.1%), or multifactorial (22.2%). Overall, patient decline of colonoscopy (35.2%) was the most common reason. In a cohort of veterans with positive results from FITs during CRC screening, reasons for lack of follow-up colonoscopy varied and included patient, provider, and system factors. These findings can be used to reduce barriers to follow-up colonoscopy and to address system-level challenges in scheduling and attrition for colonoscopy.

Waiting for diagnostic colonoscopy: a qualitative exploration of screening participants' experiences in a FIT-based colorectal cancer screening program.

BackgroundParticipants in population-based screening for colorectal cancer (CRC) may experience increased anxiety immediately after a positive screening test, but research in this area is limited. The objective of this study was to explore how screening participants experience a positive test result and cope with the pre-diagnostic waiting period in a CRC screening program.Materials and methodsScreening participants with a positive fecal immunochemical test (FIT) result were identified in the Danish national CRC program before they attended diagnostic colonoscopy. Sixteen screening participants were selected for an interview in their own homes, using a semi-structured interview guide. Transcribed data were analyzed thematically.ResultsThe most prominent themes were symptom appraisal and communication strategies. Most participants attributed the positive FIT result showing blood in the stool to pre-existing non-malignant conditions but a few were very worried about the FIT result and the outcome of the colonoscopy. Communication strategies included discussions with family or friends about the positive FIT result and the upcoming colonoscopy, or containing information until the colonoscopy had provided the definitive diagnostic result. There was no apparent need for communication with health care professionals during the pre-diagnostic waiting period.ConclusionThe pre-diagnostic waiting period between positive FIT result and colonoscopy in a population-based screening program may cause worry for some participants, potentially to require support, but most people consider it unconcerning. Screening providers should communicate to all screening participants in written form that negative emotional responses may occur after a positive screening result. This is particularly important in screening programs using self-sample kits without the presence of a health care professional to reassure the few participants who may experience significant anxiety.

Yield of Colonoscopy After a Positive Result From a Fecal Immunochemical Test OC-Light

The fecal immunochemical test (FIT) is widely used in colorectal cancer (CRC) screening. The OC-Light FIT is 1 of 2 FITs recommended for CRC screening by the Preventive Services Task Force guidelines. However, little is known about its ability to detect CRC in large average-risk populations. We performed a retrospective cohort study of patients (50-75 years old) in the San Francisco Health Network who were screened for CRC by OC-Light FIT from August 2010 through June2015. Patients with a positive result were referred for colonoscopy. We used electronic health records to identify participants with positive FIT results, and collected results from subsequent colonoscopies and pathology analyses. The FIT positive rate was calculated by dividing the number of positive FIT results by the total number of FIT tests completed. The primary outcome was the positive rate from OC-Light FIT and yield of neoplasms at colonoscopy. Secondary outcomes were findings from first vs subsequent rounds of testing, and how these varied by sexand race. We collected result from 35,318 FITs, performed on 20,886 patients; 2930 patients (8.3%) had a positive result, and 1558 patients completed the follow-up colonoscopy. A positive result from the FIT identified patients with CRC with a positive predictive value of 3.0%, and patients with advanced adenoma with a positive predictive value of 20.8%. The FIT positive rate was higher during the first round of testing (9.4%) compared to subsequent rounds (7.4%) (P < .01). The yield of CRC in patients with a positive result from the first round of the FIT was 3.7%, and decreased to 1.8% for subsequent rounds (P= .02). In a retrospective analysis of patients in a diverse safety-net population who underwent OC-Light FIT for CRC screening, we found that approximately 3% of patients with a positive result from a FIT to have CRC and approximately 21% to have advanced adenoma.

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.

LGALS4, CEACAM6, TSPAN8, and COL1A2: Blood Markers for Colorectal Cancer—Validation in a Cohort of Subjects With Positive Fecal Immunochemical Test Result

BackgroundA noninvasive blood test for the early detection of colorectal cancer (CRC) is highly required. We evaluated a panel of 4 mRNAs as putative markers of CRC. Materials and MethodsWe tested LGALS4, CEACAM6, TSPAN8, and COL1A2, referred to as the CELTiC panel, using quantitative reverse transcription polymerase chain reaction, on subjects with positive fecal immunochemical test (FIT) results and undergoing colonoscopy. Using a nonparametric test and multinomial logistic model, FIT-positive subjects were compared with CRC patients and healthy individuals. ResultsAll the genes of the CELTiC panel displayed statistically significant differences between the healthy subjects (n = 67), both low-risk (n = 36) and high-risk/CRC (n = 92) subjects, and those in the negative-colonoscopy, FIT-positive group (n = 36). The multinomial logistic model revealed LGALS4 was the most powerful marker discriminating the 4 groups. When assessing the diagnostic values by analysis of the areas under the receiver operating characteristic curves (AUCs), the CELTiC panel reached an AUC of 0.91 (sensitivity, 79%; specificity, 94%) comparing normal subjects to low-risk subjects, and 0.88 (sensitivity, 75%; specificity, 87%) comparing normal and high-risk/CRC subjects. The comparison between the normal subjects and the negative-colonoscopy, FIT-positive group revealed an AUC of 0.93 (sensitivity, 82%; specificity, 97%). ConclusionThe CELTiC panel could represent a useful tool for discriminating subjects with positive FIT findings and for the early detection of precancerous adenomatous lesions and CRC.

Is It Necessary to Repeat Fecal Occult Blood Tests with Borderline Results for Colorectal Cancer Screening?

The fecal immunochemical test (FIT) is the initial non-invasive investigation of choice for population-based colorectal cancer (CRC) screening. We evaluated the positivity rate in repeated tests using the same fecal specimen that showed borderline results in the FIT. A total of 6,465 patients were tested with the FIT in a tertiary-care hospital from July to December 2016. FIT was done using OC-Sensor PLEDIA (Eiken Chemical Co., Tokyo, Japan). Among 6,465 patients, 364 (5.6%) patients showed a positive FIT result of over 20 µg Hb/g feces. A total of 112 (1.7%) patients showed borderline scores of 10.2–20 µg Hb/g feces, and 5,989 (92.6%) patients showed negative results of less than 10 µg Hb/g feces. Among the 101 repeat-tested patients, 19 (18.8%) of the patients' scores converted to levels above the positive cut-off threshold. Repeated results of 19 patients showed score elevations from 20.2 to 68 µg Hb/g feces. These results suggest that it is most important to analyze properly prepared samples, even if only once. Therefore, the laboratory staff should ensure the proper preparation of stool specimens for FIT. Laboratory directors should choose the best cut-off value for detecting CRC at their respective institutions.

Screening for colorectal cancer in Tianhe, Guangzhou: results of combining fecal immunochemical tests and risk factors for selecting patients requiring colonoscopy.

ObjectiveTo explore the performance of a protocol combining fecal immunochemical test (FIT) and a high-risk factor questionnaire (HRFQ) for selecting patients requiring colonoscopy as part of a population-based colorectal cancer (CRC) screening program in China.MethodsFrom 2015 to 2016, we conducted a CRC screening program for all residents aged 45 years or older in Tianhe District, Guangzhou City, China. Participants underwent an FIT and received an HRFQ as part of primary screening. Those with positive FIT and/or HRFQ results were considered to be at high risk and were recommended to undergo colonoscopy.ResultsA total of 10 074 subjects were recruited and enrolled in the screening program. In the enrolled population, 17.5% had positive FIT results and 19.4% had positive HRFQ results. Of those recommended to undergo diagnostic colonoscopy, 773 did so. The screening method’s overall positive predictive value (PPV) was 4.9% for non-adenomatous polyps, 11.4% for low-risk adenomas (LRAs), 15.9% for high-risk adenomas (HRAs) and 1.6% for CRC. The PPVs of positive FIT results for non-adenomatous polyps, LRAs, HRAs and CRC were 5.2%, 15.9%, 22.5% and 2.5%, respectively. The PPVs of positive HRFQ results for non-adenomatous polyps, LRA, HRA and CRC were 4.1%, 10.2%, 14.3% and 1.4%, respectively. The PPVs associated with combined positive FIT and HRFQ results for non-adenomatous polyps, LRAs, HRAs and CRC were 4.5%, 16.4%, 23.7% and 2.8%, respectively.ConclusionOur results suggest that this two-step CRC screening strategy, involving a combination of FIT and HRFQ followed by colonoscopy, is useful to identify early-stage CRC. The high detection rates and PPVs for CRC and adenomas encourage this strategy’s use in ongoing screening programs.

Interval Colorectal Cancer Incidence Among Subjects Undergoing Multiple Rounds of Fecal Immunochemical Testing

Among subjects screened for colorectal cancer (CRC) by the guaiac fecal occult blood test, interval cancers develop in 48% to 55% of the subjects. Data are limited on how many persons screened by fecal immunochemical tests (FIT), over multiple rounds, develop interval cancers. In the Netherlands, a pilot FIT-based biennial CRC screening program was conducted between 2006 and 2014. We collected and analyzed data from the program on CRCs detected during screening (SD-CRC) and CRCs not detected within the screening program (non-SD-CRC; such as FIT interval cancers, colonoscopy interval cancers, and cancer in nonparticipants). Screenees with a negative FIT result received a letter explaining that no blood had been detected in the stool sample and were re-invited, if eligible, for screening biennially. Screenees with a positive FIT result (hemoglobin concentration of 10 μg Hb/g feces) were invited for consultation and scheduled for colonoscopy; results were collected. After the fourth round of FIT screening, the cohort was linked to the Netherlands Cancer Registry, through March 31, 2015; participant characteristics, data on tumor stage, location (at time of resection), and survival status were collected for all identified CRC cases. A reference group comprised all persons with CRC diagnosed in the Netherlands general population during the same period, in the same age range (50-76 years), who had not been offered CRC screening. The median time between invitations (2.37 years) was used as a cutoff to categorize participants within the FIT interval cancer category. We compared participant characteristics, tumor characteristics, and mortality among subjects with SD-CRC and with non-SD-CRC. A total of 27,304 eligible individuals were invited for FIT screening, of whom 18,716 (69%) participated at least once. Of these, 3005 (16%) had a positive result from the FIT in 1 of the 4 screening rounds. In total, CRC was detected in 261 participants: 116 SD-CRCs and 145 non-SD-CRCs (27 FIT interval cancers, 9 colonoscopy interval cancers, and 109 CRCs in nonparticipants). The FIT interval cancer proportion after 3 completed screening rounds was 23%. Participants with SD-CRC had more early-stage tumors than participants with non-SD-CRCs (P < .001). Of persons with SD-CRC and FIT interval cancers, significantly higher proportions survived (89% and 81%, respectively) compared withpersons with colonoscopy interval cancers (44% survival) and nonparticipants with CRC (60% survival) (P < .001). In an analysis of data from a pilot FIT-based biennial screening program, we found that among persons screened by FIT, 23% developed FIT interval cancer. FIT therefore detects CRC with 77% sensitivity. The proportion of FIT interval cancers in FIT screening appears to be lower than that with guaiac fecal occult blood testing. Clinical trial registry: yes, www.trialregister.nl, trial number: NTR5385.

Association Between Time to Colonoscopy After a Positive Fecal Test Result and Risk of Colorectal Cancer and Cancer Stage at Diagnosis

The fecal immunochemical test (FIT) is commonly used for colorectal cancer screening and positive test results require follow-up colonoscopy. However, follow-up intervals vary, which may result in neoplastic progression. To evaluate time to colonoscopy after a positive FIT result and its association with risk of colorectal cancer and advanced-stage disease at diagnosis. Retrospective cohort study (January 1, 2010-December 31, 2014) within Kaiser Permanente Northern and Southern California. Participants were 70 124 patients aged 50 through 70 years eligible for colorectal cancer screening with a positive FIT result who had a follow-up colonoscopy. Time (days) to colonoscopy after a positive FIT result. Risk of any colorectal cancer and advanced-stage disease (defined as stage III and IV cancer). Odds ratios (ORs) and 95% CIs were adjusted for patient demographics and baseline risk factors. Of the 70 124 patients with positive FIT results (median age, 61 years [IQR, 55-67 years]; men, 52.7%), there were 2191 cases of any colorectal cancer and 601 cases of advanced-stage disease diagnosed. Compared with colonoscopy follow-up within 8 to 30 days (n = 27 176), there were no significant differences between follow-up at 2 months (n = 24 644), 3 months (n = 8666), 4 to 6 months (n = 5251), or 7 to 9 months (n = 1335) for risk of any colorectal cancer (cases per 1000 patients: 8-30 days, 30; 2 months, 28; 3 months, 31; 4-6 months, 31; and 7-9 months, 43) or advanced-stage disease (cases per 1000 patients: 8-30 days, 8; 2 months, 7; 3 months, 7; 4-6 months, 9; and 7-9 months, 13). Risks were significantly higher for examinations at 10 to 12 months (n = 748) for any colorectal cancer (OR, 1.48 [95% CI, 1.05-2.08]; 49 cases per 1000 patients) and advanced-stage disease (OR, 1.97 [95% CI, 1.14-3.42]; 19 cases per 1000 patients) and more than 12 months (n = 747) for any colorectal cancer (OR, 2.25 [95% CI, 1.89-2.68]; 76 cases per 1000 patients) and advanced-stage disease (OR, 3.22 [95% CI, 2.44-4.25]; 31 cases per 1000 patients). Among patients with a positive fecal immunochemical test result, compared with follow-up colonoscopy at 8 to 30 days, follow-up after 10 months was associated with a higher risk of colorectal cancer and more advanced-stage disease at the time of diagnosis. Further research is needed to assess whether this relationship is causal.

A Combination of Fecal Immunochemical Test Results and Iron Deficiency Anemia for Detection of Advanced Colorectal Neoplasia in Asymptomatic Men.

PurposeA substantial proportion of patients with colorectal cancer (CRC) present with iron deficiency anemia (IDA), and fecal immunochemical test (FIT) has proven to be an effective method for detecting the majority of CRC cases. A combination strategy of FIT results and IDA may be useful for risk stratification for detecting advanced colorectal neoplasia (ACRN). We compared the prevalence of ACRN among four groups stratified by FIT results and the presence of IDA.Materials and MethodsA cross-sectional study was performed on asymptomatic male participants who underwent both FIT and colonoscopy between 2010 and 2014 as part of a comprehensive health screening program in Korea.ResultsOf 17236 participants, 522 (3.0%) showed positive FIT results and 26 (0.2%) had IDA. The mean age of the study participants was 40.8 years. The participants were classified into four groups: positive FIT result/IDA (G1, n=7), positive FIT result/no IDA (G2, n=515), negative FIT result/IDA (G3, n=19), and negative FIT result/no IDA (G4, n=16695). The prevalences of ACRN in G1, G2, G3, and G4 were 28.6, 13.4, 5.3, and 1.5%, respectively (p<0.001) and those of CRC were 28.6, 1.6, 0.0, and 0.01%, respectively (p<0.001). Subjects with positive FIT results and IDA had an increased risk of ACRN and CRC in both group aged <50 and ≥50 years.ConclusionSubjects with positive FIT results and IDA had an increased risk of ACRN. Our results suggest that a combination strategy of FIT and IDA may be helpful in selecting and prioritizing asymptomatic men for colonoscopy.