Multitarget Stool DNA Test Performance in an Average-Risk Colorectal Cancer Screening Population

Abstract

INTRODUCTION: We set out to evaluate the performance of a multitarget stool DNA (MT-sDNA) in an average-risk colonoscopy-controlled colorectal cancer (CRC) screening population. MT-sDNA stool test results were evaluated against fecal immunochemical test (FIT) results for the detection of different lesions, including molecularly defined high-risk adenomas and several other tumor characteristics. METHODS: Whole stool samples (n 5 1,047) were prospectively collected and subjected to an MT-sDNA test, which tests for KRAS mutations, NDRG4 and BMP3 promoter methylation, and hemoglobin. Results for detecting CRC (n 5 7), advanced precancerous lesions (advanced adenoma [AA] and advanced serrated polyps; n 5 119), and non-AAs (n 5 191) were compared with those of FIT alone (thresholds of 50, 75, and 100 hemoglobin/mL). AAs with high risk of progression were defined by the presence of specific DNA copy number events as measured by low-pass whole genome sequencing. RESULTS: The MT-sDNA test was more sensitive than FIT alone in detecting advanced precancerous lesions (46% (55/119) vs 27% (32/119), respectively, P < 0.001). Specificities among individuals with nonadvanced or negative findings (controls) were 89% (791/888) and 93% (828/888) for MT-sDNA and FIT testing, respectively. A positive MT-sDNA test was associated with multiple lesions (P 5 0.005), larger lesions (P 5 0.03), and lesions with tubulovillous architecture (P 5 0.04). The sensitivity of the MT-sDNA test or FIT in detecting individuals with high-risk AAs (n 5 19) from individuals with low-risk AAs (n 5 52) was not significantly different.

A Novel Xenonucleic Acid Mediated Molecular Clamping Technology for Early Colorectal Cancer Screening

“…Cologuard (Exact Sciences Corporation), Epi ProColon® (Epigenomics AG), However, these FDA approved assays are based on only a single gene methylation detection (Septin 9-Epi ProColon) or 2 methylation biomarkers combined with only one target gene mutation assay (Cologuard) which potentially limits assay sensitivity. In this study we have preliminary shown that ColoScape TM can detect 66.6% of mutations from advanced adenoma (AA) samples although its only 10 samples which needs further con rmed, while the reported Cologuard AA detection rate is 42-46% 44,45 . This suggests that…”

COVID-19 and the Global Impact on Colorectal Practice and Surgery

“…Both of these tests have proven excellent accuracy for excluding colon cancer. [29][30][31] Unpublished data from the NICE FIT study which examined the role of FIT on 9822 patients referred with both high-and low-risk symptoms, found that for a threshold of 10 mg hemoglobin/1 g, the negative predictive value was 99.6%. Thus, a negative FIT result can provide reassurance because the chance of the patient not having cancer is 99.6%.…”

“…32 The FIT-DNA has increased sensitivity for detecting advanced precancerous lesions compared with FIT alone when screening a population with an average risk of colorectal cancer. 30 Mowat et al 33 reported that the use of such noninvasive tests could reduce the burden required by invasive tests by > 40%. Because most nations that have been debilitated by the COVID-19 pandemic are now beyond the curve (ie, effective reproduction number < 1) and in the recovery phase, a stepwise resumption of prioritized elective endoscopy services can begin, guided by available hospital endoscopy space, the availability of personnel and equipment supplies, and increased infection prevention training and selfprotection for staff.…”

COVID-19: An Opportunity to Reimagine Colorectal Cancer Diagnostic Testing—A New Paradigm Shift

“…In addition, the mSEPT9 test is not widely available outside of the United States, although it has been approved by the US Preventative Services Task Force as a first-line CRC screening test. 13 …”

“…Thus, it will have a greater number of false-positive results and a greater likelihood of requiring follow-up colonoscopy and an associated adverse event per screening test. 13 , 15 Furthermore, the FIT-DNA is not readily available outside the United States.…”