Multitarget stool DNA testing for the prevention of colon cancer: outcomes in a large integrated healthcare system

Vakil, Nimish; Ciezki, Kristin; Huq, Nadia; Singh, Maharaj

doi:10.1016/j.gie.2019.12.027

Cited by 16 publications

(11 citation statements)

References 20 publications

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“…We had the unique opportunity to assess and report on a large singlecenter experience for comparing these screening tests. Our positive predictive value results from clinical screening with mt-sDNA matched closely with those from the large clinical Because mt-sDNA is commonly considered a cancer detection test, it may come as somewhat of a surprise that fewer than 2% of positive results were due to cancer in our practice, similar to other clinical experiences (3)(4)(5). Put another way, more than 98% of mt-sDNA tests with positive results could be considered to have false-positive results for cancer, although this misses the point of CRC screening.…”

Section: Discussionsupporting

confidence: 81%

Diagnostic Performance of Multitarget Stool DNA and CT Colonography for Noninvasive Colorectal Cancer Screening

et al. 2020

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O ptical colonoscopy remains the dominant strategy for colorectal cancer (CRC) screening in the United States and is used for both cancer prevention and detection. However, optical colonoscopy is an invasive and resourceintense primary screening examination. Less invasive CRC screening tests provide an alternative, complementary option for population-based screening; patients with positive results are referred for optical colonoscopy as the de facto therapeutic standard. However, these noninvasive tests may differ in their ability to prevent CRC through the detection of advanced precancerous polyps. Available noninvasive screening examinations that are approved by the U.S. Food and Drug Administration include stool-based tests and CT colonography. Vast previous screening experiences with fecal occult blood and immunochemical testing have been published previously (1), but the data for multitarget stool DNA (mt-sDNA) and CT colonography screening are limited, and these tests were only recently included in the U.S. Preventive Services Task Force guidelines (2). Data are just now emerging on the postapproval clinical screening experience with the Cologuard (Exact Sciences, Madison, Wis) mt-sDNA test (3-5). Nonetheless, nationwide use of this stool-based test has dramatically increased since its simultaneous approval was granted in August 2014 by the U.S. Food and Drug Administration and the Centers for Medicare and Medicaid Services. Since then, millions of screening tests have been performed. Published data on CT colonography screening are mainly limited to trial data and clinical practice at a single center (6-9). Clinical validation trials (8-10) can derive the sensitivity and specificity of these noninvasive tests for key outcomes such as advanced neoplasia and CRC because every patient undergoes the reference standard, optical colonoscopy. However, in actual clinical practice, diagnostic evaluation

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Section: Discussionsupporting

confidence: 81%

Diagnostic Performance of Multitarget Stool DNA and CT Colonography for Noninvasive Colorectal Cancer Screening

et al. 2020

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“…The association of a positive mt-sDNA with neoplasia in our study (68.0%) exceeded that reported by Imperiale et al (55%) 4 and Vakil et al (61.5%), 5 and was closer to the rate observed by Johnson et al (70%). 9 Factors that may have resulted in an increased rate of true positives in more recent studies compared with Imperiale et al include changing practice patterns with heightened attention to endoscopy quality, 18 including the use of split bowel preparation and increased average withdrawal time.…”

Section: Discussionsupporting

confidence: 69%

“…A recent study used electronic health record data to assess outcomes of mt-sDNA testing in a single integrated health care system 5 ; however, data remains limited on use of mt-sDNA and follow-up colonoscopy in community practice. Therefore, we investigated colonoscopy outcomes and colonoscopy quality measures for mt-sDNA-positive patients in the statewide, population-based New Hampshire Colonoscopy Registry (NHCR), which has collected comprehensive data on > 200,000 colonoscopies from endoscopists and patients at diverse rural and urban, academic, ambulatory and community endoscopy practices across New Hampshire since 2004.…”

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confidence: 99%

Colorectal Neoplasia Detection in Individuals With Positive Multitarget Stool DNA Tests

Anderson

Robinson

Hisey³

et al. 2021

Journal of Clinical Gastroenterology

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Background: The US Preventive Services Task Force (USPSTF) includes multitarget stool DNA (mt-sDNA) testing as a colorectal cancer (CRC) screening option in average-risk individuals, but data on colonoscopy outcomes after positive mt-sDNA tests in community settings are needed. Aim: The aim of this study was to investigate colonoscopy outcomes and quality following positive mt-sDNA in the population-based New Hampshire Colonoscopy Registry. Methods: We compared colonoscopy outcomes and quality between age-matched, sex-matched, and risk-matched patients from 30 endoscopy practices with and without a preceding positive mt-sDNA test. Main outcomes were colonoscopy findings of CRC, advanced noncancerous neoplasia, nonadvanced neoplasia, or normal examination. Quality measures included withdrawal time, bowel preparation quality, examination completion, and percentage of average-risk individuals with normal colonoscopies receiving a USPSTF-recommended 10 year rescreening interval. Results: Individuals with positive mt-sDNA tests (N=306, average age 67.0 y; 61.8% female) were significantly more likely than colonoscopy-only patients (N=918, 66.2 y; 61.8% female) to have CRC (1.3% vs. 0.4%) or advanced noncancerous neoplasia (27.1% vs. 8.2%) (P<0.0001). Neoplasia was found in 68.0% of patients having colonoscopy after a positive mt-sDNA test, (positive predictive value, was 68.0%), versus 42.3% of patients with colonoscopy only (P<0.0001). No significant differences in colonoscopy quality measures were observed between cohorts. Conclusions: Colonoscopy after a positive mt-sDNA test was more frequently associated with CRC and colorectal neoplasia than colonoscopy alone. Positive mt-sDNA tests can enrich the proportion of colonoscopies with clinically relevant findings. Follow-up recommendations suggest that endoscopists do not inappropriately shorten rescreening intervals in mt-sDNA-positive patients with normal colonoscopy. These findings support the clinical utility of mt-sDNA for CRC screening in community practice.

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“…The use of the mt-DNA test was approved for clinical use by the USFDA in 2014. A more recent retrospective cohort study [85] confirmed the ability of the mt-SDBA test to detect early-stage cancers (18% tested positive, with fewer than 1% having colorectal cancer and 60% having adenomas), though there were high false-positive rates (39% deemed false-positive) [85]. Other studies have also looked at testing stool for DNA, showing good potential for use in screening [86,87].…”

Section: Dna-based Molecular Markers and Testsmentioning

confidence: 90%

Colorectal Cancer Diagnosis: The Obstacles We Face in Determining a Non-Invasive Test and Current Advances in Biomarker Detection

Kamel

Eltarhoni

Nisar

et al. 2022

Cancers

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Globally, colorectal cancer (CRC) is the third most common cancer, with 1.4 million new cases and over 700,000 deaths per annum. Despite being one of the most common cancers, few molecular approaches to detect CRC exist. Carcinoembryonic antigen (CEA) is a known serum biomarker that is used in CRC for monitoring disease recurrence or response to treatment. However, it can also be raised in multiple benign conditions, thus having no value in early detection or screening for CRC. Molecular biomarkers play an ever-increasing role in the diagnosis, prognosis, and outcome prediction of disease, however, only a limited number of biomarkers are available and none are suitable for early detection and screening of CRC. A PCR-based Epi proColon® blood plasma test for the detection of methylated SEPT9 has been approved by the USFDA for CRC screening in the USA, alongside a stool test for methylated DNA from CRC cells. However, these are reserved for patients who decline traditional screening methods. There remains an urgent need for the development of non-invasive molecular biomarkers that are highly specific and sensitive to CRC and that can be used routinely for early detection and screening. A molecular approach to the discovery of CRC biomarkers focuses on the analysis of the transcriptome of cancer cells to identify differentially expressed genes and proteins. A systematic search of the literature yielded over 100 differentially expressed CRC molecular markers, of which the vast majority are overexpressed in CRC. In terms of function, they largely belong to biological pathways involved in cell division, regulation of gene expression, or cell proliferation, to name a few. This review evaluates the current methods used for CRC screening, current availability of biomarkers, and new advances within the field of biomarker detection for screening and early diagnosis of CRC.

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Multitarget stool DNA testing for the prevention of colon cancer: outcomes in a large integrated healthcare system

Cited by 16 publications

References 20 publications

Diagnostic Performance of Multitarget Stool DNA and CT Colonography for Noninvasive Colorectal Cancer Screening

Diagnostic Performance of Multitarget Stool DNA and CT Colonography for Noninvasive Colorectal Cancer Screening

Colorectal Neoplasia Detection in Individuals With Positive Multitarget Stool DNA Tests

Colorectal Cancer Diagnosis: The Obstacles We Face in Determining a Non-Invasive Test and Current Advances in Biomarker Detection

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