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Multitarget Stool mRNA Test for Detecting Colorectal Cancer Lesions Including Advanced Adenomas.

ABSTRACT: Current approved non-invasive screening methods for colorectal cancer (CRC) include FIT and DNA-FIT testing, but their efficacy for detecting precancerous lesions that are susceptible to progressing to CRC such as advanced adenomas (AA) remains limited, thus requiring further options to improve the detection of CRC lesions at earlier stages. One of these is host mRNA stool testing. The aims of the present study were to identify specific stool mRNA targets that can predict AA and to investigate their stability under a clinical-like setting. A panel of mRNA targets was tested on stool samples obtained from 102 patients including 78 CRC stage I-III and 24 AA as well as 32 healthy controls. Area under the receiver operating characteristic (ROC) curves were calculated to establish sensitivities and specificities for individual and combined targets. Stability experiments were performed on freshly obtained specimens. Six of the tested targets were found to be specifically increased in the stools of patients with CRC and three in the stools of both AA and CRC patients. After optimization for the choice of the 5 best markers for AA and CRC, ROC curve analysis revealed overall sensitivities of 75% and 89% for AA and CRC, respectively, for a ≥95% specificity, and up to 75% and 95% for AA and CRC, respectively, when combined with the FIT score. Targets were found to be stable in the stools up to 3 days at room temperature. In conclusion, these studies show that the detection of host mRNA in the stools is a valid approach for the screening of colorectal cancerous lesions at all stages and is applicable to a clinical-like setup.

SUBMITTER: Herring E

PROVIDER: S-EPMC7998137 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Colorectal Cancer Screening With the Multitarget Stool DNA Test.

Project description: Not available

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Early Adoption of a Multitarget Stool DNA Test for Colorectal Cancer Screening.

Project description:ObjectivesTo characterize early adoption of a novel multitarget stool DNA (MT-sDNA) screening test for colorectal cancer (CRC) screening and to test the hypothesis that adoption differs by demographic characteristics and prior CRC screening behavior and proceeds predictably over time.Patients and methodsWe used the Rochester Epidemiology Project research infrastructure to assess the use of the MT-sDNA screening test in adults aged 50 to 75 years living in Olmsted County, Minnesota, in 2014 and identified 27,147 individuals eligible or due for screening colonoscopy from November 1, 2014, through November 30, 2015. We used electronic Current Procedure Terminology and Health Care Common Procedure codes to evaluate early adoption of the MT-sDNA screening test in this population and to test whether early adoption varies by age, sex, race, and prior CRC screening behavior.ResultsOverall, 2193 (8.1%) and 974 (3.6%) individuals were screened by colonoscopy and MT-sDNA, respectively. Age, sex, race, and prior CRC screening behavior were significantly and independently associated with MT-sDNA screening use compared with colonoscopy use after adjustment for all other variables (P<.05 for all). The rates of adoption of MT-sDNA screening increased over time and were highest in those aged 50 to 54 years, women, whites, and those who had a history of screening. The use of the MT-sDNA screening test varied predictably by insurance coverage. The rates of colonoscopy decreased over time, whereas overall CRC screening rates remained steady.ConclusionThe results of the present study are generally consistent with predictions derived from prior research and the diffusion of innovation framework, pointing to increasing use of the new screening test over time and early adoption by younger patients, women, whites, and those with prior CRC screening.

| S-EPMC5505626 | biostudies-literature

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

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Project description:BackgroundIn 2014, the Centers for Medicare and Medicaid Services (CMS) began covering a multitarget stool DNA (mtSDNA) test for colorectal cancer (CRC) screening of Medicare beneficiaries. In this study, we evaluated whether mtSDNA testing is a cost-effective alternative to other CRC screening strategies reimbursed by CMS, and if not, under what conditions it could be.MethodsWe use three independently-developed microsimulation models to simulate a cohort of previously unscreened US 65-year-olds who are screened with triennial mtSDNA testing, or one of six other reimbursed screening strategies. Main outcome measures are discounted life-years gained (LYG) and lifetime costs (CMS perspective), threshold reimbursement rates, and threshold adherence rates. Outcomes are expressed as the median and range across models.ResultsCompared to no screening, triennial mtSDNA screening resulted in 82 (range: 79-88) LYG per 1,000 simulated individuals. This was more than for five-yearly sigmoidoscopy (80 (range: 71-89) LYG), but fewer than for every other simulated strategy. At its 2017 reimbursement rate of $512, mtSDNA was the most costly strategy, and even if adherence were 30% higher than with other strategies, it would not be a cost-effective alternative. At a substantially reduced reimbursement rate ($6-18), two models found that triennial mtSDNA testing was an efficient and potentially cost-effective screening option.ConclusionsCompared to no screening, triennial mtSDNA screening reduces CRC incidence and mortality at acceptable costs. However, compared to nearly all other CRC screening strategies reimbursed by CMS it is less effective and considerably more costly, making it an inefficient screening option.

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Project description:IntroductionEffective colorectal cancer (CRC) prevention and screening requires sensitive detection of all advanced neoplasias (CRC and advanced adenomas [AA]). However, existing noninvasive screening approaches cannot accurately detect adenomas with high sensitivity.MethodsHere, we describe a multifactor assay (RNA-FIT test) that combines 8 stool-derived eukaryotic RNA biomarkers, patient demographic information (smoking status), and a fecal immunochemical test (FIT) to sensitively detect advanced colorectal neoplasias and other non-advanced adenomas in a 1,305-patient, average-risk, prospective cohort. This cohort was supplemented with a 22-patient retrospective cohort consisting of stool samples obtained from patients diagnosed with AA or CRC before treatment or resection. Participants within these cohorts were evaluated with the RNA-FIT assay and an optical colonoscopy. RNA-FIT test results were compared with colonoscopy findings.ResultsModel performance was assessed through 5-fold internal cross-validation of the training set (n = 939) and by using the model on a hold out testing set (n = 388). When used on the hold out testing set, the RNA-FIT test attained a 95% sensitivity for CRC (n = 22), 62% sensitivity for AA (n = 52), 25% sensitivity for other non-AA (n = 139), 80% specificity for hyperplastic polyps (n = 74), and 85% specificity for no findings on a colonoscopy (n = 101).DiscussionThe RNA-FIT assay demonstrated clinically relevant detection of all grades of colorectal neoplasia, including carcinomas, AAs, and ONAs. This assay could represent a noninvasive option to screen for both CRC and precancerous adenomas.

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The stool DNA test is more accurate than the plasma septin 9 test in detecting colorectal neoplasia.

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Sessile serrated polyp detection rates after fecal immunochemical test or multitarget stool DNA test: Systematic review and meta-analysis

Project description: Not available

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