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New Fecal Bacterial Signature for Colorectal Cancer Screening Reduces the Fecal Immunochemical Test False-Positive Rate in a Screening Population
23 Pages Posted: 20 Jul 2020
More...Abstract
Background: 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.
Methods: 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.
Findings: 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 µg/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%.
Interpretation: 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.
Funding: Spanish Ministry of Economy, Industry and Competitivity (MINECO), NEOTEC
Declaration of Interests: Prof. Garcia-Gil, Dr. Aldeguer, Dr. Serra-Pagès, Dr. Serrano, Dr. Ramió-Pujol, Mr. Amoedo, Ms. Oliver, Dr. Malagón are employees from GoodGut, company who has received private and public funding. Prof. Garcia-Gil, Dr. Aldeguer, Dr. Serra-Pagès, Dr. Serrano, Dr. Ramió Pujol, Mr. Amoedo, Ms. Oliver and Dr. Malagón report grants from MINECO and from CDTI, during the conduct of the study. Prof. Garcia-Gil, Dr. Aldeguer, Dr. Serra-Pagès, and Dr. Guardiola are also GoodGut shareholders, outside the submitted work. Prof. Garcia-Gil, Dr. Aldeguer, and Dr. Serra-Pagès have two licensed patents to GoodGut: EP14382074.4 and PCT/EP2015/054451. The rest of the authors have nothing to disclose.
Ethics Approval Statement: The study protocol (clinical investigation code: RAID-CRC 20202015) was approved by the Clinical Research Ethics Committee of the three participating centers. Written informed consent was obtained from all participants.
Keywords: Colorectal cancer, fecal immunochemical test, bacterial markers, microbiota, qPCR, screening
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