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New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population.

ABSTRACT: Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal bacterial markers capable of decreasing FIT false-positive rates in a FIT-positive population. We defined a fecal bacterial signature (RAID-CRC Screen) in a proof-of-concept with 172 FIT-positive individuals and validated the obtained results on an external cohort of 327 FIT-positive subjects. All study participants had joined the national CRC screening program. In the clinical validation of RAID-CRC Screen, a sensitivity of 83.9% and a specificity of 16.3% were obtained for the detection of advanced neoplasm lesions (advanced adenomas and/or CRC). FIT 20 ?g/g produced 184 false-positive results. Using RAID-CRC Screen, this value was reduced to 154, thus reducing the false-positive rate by 16.3%. The RAID-CRC Screen test could be implemented in CRC screening programs to allow a significant reduction in the number of colonoscopies performed unnecessarily for FIT-positive participants of CRC screening programs.

SUBMITTER: Malagon M

PROVIDER: S-EPMC7707514 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population.

Malagón Marta M Ramió-Pujol Sara S Serrano Marta M Amoedo Joan J Oliver Lia L Bahí Anna A Miquel-Cusachs Josep Oriol JO Ramirez Manel M Queralt-Moles Xavier X Gilabert Pau P Saló Joan J Guardiola Jordi J Piñol Virginia V Serra-Pagès Mariona M Castells Antoni A Aldeguer Xavier X Garcia-Gil L Jesús LJ

PloS one 20201201 12

Guidelines recommend routine screening for colorectal cancer (CRC) in asymptomatic adults starting at age 50. The most extensively used noninvasive test for CRC screening is the fecal immunochemical test (FIT), which has an overall sensitivity for CRC of approximately 61.0%-91.0%, which drops to 27.0%-67.0% for advanced adenomas. These figures contain a high false-positive rate and a low positive predictive value. This work aimed to develop a new, noninvasive CRC screening tool based on fecal ba ...[more]

PMID: 33259546

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Project description:BackgroundMany screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series (n = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program.MethodThe mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants.DiscussionThe outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening.Trial registrationClinicaltrials.gov ; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist =.

Project description:IntroductionThe use of screening can prevent death from colorectal cancer, yet people without regular healthcare visits may not realize the benefits of this preventive intervention. The objective of this study was to determine the effectiveness of a mailed screening invitation or mailed fecal immunochemical test in increasing colorectal cancer screening uptake in veterans without recent primary care encounters.Study designThree-arm pragmatic randomized trial.Setting/participantsParticipants were screening-eligible veterans aged 50-75 years, without a recent primary care visit who accessed medical services at the Corporal Michael J. Crescenz Veteran Affairs Medical Center between January 1, 2017, and July 31, 2017. All data were analyzed from March 1, 2018, to July 31, 2018.InterventionParticipants were randomized to (1) usual opportunistic screening during a healthcare visit (n=260), (2) mailed invitation to screen and reminder phone calls (n=261), or (3) mailed fecal immunochemical test outreach plus reminder calls (n=61).Main outcome measuresThe main outcome under investigation was the completion of colorectal cancer screening within 6 months after randomization.ResultsOf 782 participants in the trial, 53.9% were aged 60-75 years and 59.7% were African American. The screening rate was higher in the mailed fecal immunochemical test group (26.1%) compared with usual care (5.8%) (rate difference=20.3%, 95% CI=14.3%, 26.3%; RR=4.52, 95% CI=2.7, 7.7) or screening invitation (7.7%) (rate difference=18.4%, 95% CI=12.2%, 24.6%; RR=3.4, 95% CI=2.1, 5.4). Screening completion rates were similar between invitation and usual care (rate difference=1.9%, 95% CI= -2.4%, 6.2%; RR=1.3, 95% CI=0.7, 2.5).ConclusionsMailed fecal immunochemical test screening promotes colorectal cancer screening participation among veterans without a recent primary care encounter. Despite the addition of reminder calls, an invitation letter was no more effective in screening participation than screening during outpatient appointments.Trial registrationThis study is registered at clinicaltrials.gov NCT02584998.

Project description:BACKGROUND & AIMS:Biomarker assays could increase the accuracy of noninvasive detection of colorectal cancer (CRC); fecal immunochemical tests (FITs) are estimated to miss 27%-47% of CRCs and 70%-80% of advanced adenomas per round of screening. We investigated the conditions under which biomarker screens would be cost-effective compared with FIT screens of average-risk individuals. METHODS:We used the MISCAN-Colon microsimulation model to estimate the effects of various CRC screening test characteristics on life-years gained (LYG) and; age-specific all-cause mortality was based on the 2010 Dutch life tables. Simulated CRC incidence rate and CRC stage distribution were calibrated to observed data in The Netherlands from 1999 through 2003 (before opportunities for screening). Survival rates after diagnosis of CRC at an age younger than 75 years were based on CRC relative survival data from 1985 through 2004; survival for individuals diagnosed at an age of 75 years or older was adjusted to fit the observed age-increasing mortality/incidence ratio. We modeled FIT along with hypothetical biomarker tests with different test performance levels. For each biomarker test we calculated the maximum unit cost for the test to be cost-effective compared with FIT, assuming a willingness-to-pay threshold of €50,000 ($56,000) per LYG. RESULTS:Biennial FIT screening of subjects 55-75 years old provided 84.9 LYG at a cost of €122,000 ($137,000) per 1000 participants. Considering a unit cost of €7 ($8) for FIT (including kit and analysis only, excluding organizational costs), a biomarker test that detects CRC with higher levels of specificity and sensitivity (100%) and advanced adenomas at a proportionally higher level of sensitivity (53%) should never exceed a cost of €51 ($57). The threshold cost could increase to more than €200 ($224) for high-performing biomarker tests in cases of limited colonoscopy capacity or higher uptake of this test. CONCLUSIONS:By using the MISCAN-Colon microsimulation model to estimate effects of CRC screening tests, we found that for a biomarker test with increased overall performance to be cost-effective, it should not exceed 7-fold the unit cost of FIT. This maximum would increase substantially if colonoscopy becomes more expensive or scarce, or if the new test has higher screening uptake. These values could be used to estimate the added value of new biomarkers compared with current FIT screening.

Dataset Information

New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population.

Publications

New fecal bacterial signature for colorectal cancer screening reduces the fecal immunochemical test false-positive rate in a screening population.

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