Detection of Postcolonoscopy Colorectal Neoplasia by Multi-target Stool DNA.
Ontology highlight
ABSTRACT: Introduction
Significant variability between colonoscopy operators contributes to postcolonoscopy colorectal cancers (CRCs). We aimed to estimate postcolonoscopy colorectal neoplasia (CRN) detection by multi-target stool DNA (mt-sDNA), which has not previously been studied for this purpose.Methods
In a retrospective cohort of patients with +mt-sDNA and completed follow-up colonoscopy, positive predictive value (PPV) for endpoints of any CRN, advanced adenoma, right-sided neoplasia, sessile serrated polyps (SSP), and CRC were stratified by the time since previous colonoscopy (0-9, 10, and ≥11 years). mt-sDNA PPV at ≤9 years from previous average-risk screening colonoscopy was used to estimate CRN missed at previous screening colonoscopy.Results
Among the 850 studied patients with +mt-sDNA after a previous negative screening colonoscopy, any CRN was found in 535 (PPV 63%). Among 107 average-risk patients having +mt-sDNA ≤9 years after last negative colonoscopy, any CRN was found in 67 (PPV 63%), advanced neoplasia in 16 (PPV 15%), right-sided CRN in 48 (PPV 46%), and SSP in 20 (PPV 19%). These rates were similar to those in 47 additional average risk persons with previous incomplete colonoscopy and in an additional 68 persons at increased CRC risk. One CRC (stage I) was found in an average risk patient who was mt-sDNA positive 6 years after negative screening colonoscopy.Discussion
The high PPV of mt-sDNA 0-9 years after a negative screening colonoscopy suggests that lesions were likely missed on previous examination or may have arisen de novo. mt-sDNA as an interval test after negative screening colonoscopy warrants further study.
SUBMITTER: Ebner DW
PROVIDER: S-EPMC8216679 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundCurrent approaches to the detection of colorectal neoplasia associated with inflammatory bowel disease (IBD-CRN) are suboptimal.AimTo test the feasibility of using stool assay of exfoliated DNA markers to detect IBD-CRN.MethodsThis investigation comprised tissue and stool studies. In the tissue study, gene sequencing and methylation assays were performed on candidate genes using tissue DNA from 25 IBD-CRNs and from 25 IBD mucosae without CRN. Mutations on p53, APC, KRAS, BRAF or PIK3CA genes were insufficiently informative, but several aberrantly methylated genes were highly discriminant. In the stool study, we evaluated candidate methylated genes (vimentin, EYA4, BMP3, NDRG4) in a prospective blinded study on buffered stools from 19 cases with known IBD-CRN and 35 age- and sex-matched IBD controls without CRN. From stool-extracted DNA, target genes were assayed using quantitative allele-specific real-time target and signal amplification method.ResultsIBD-CRN cases included 17 with ulcerative colitis (UC) and two with Crohn's disease (CD); nine had cancer and 10 had dysplasia. Controls included 25 with UC and 10 with CD. Individually, BMP3, vimentin, EYA4 and NDRG4 markers showed high discrimination in stools with respective areas under the ROC curve of 0.91, 0.91, 0.85 and 0.84 for total IBD-CRN and of 0.97, 0.97, 0.95 and 0.85 for cancer. At 89% specificity, the combination of BMP3 and mNDRG4 detected 9/9 (100%) of CRC and 80% of dysplasia, 4/4 (100%) of high grade and 4/6 (67%) of low grade.ConclusionThese findings demonstrate the feasibility of stool DNA testing for non-invasive detection of colorectal neoplasia associated with inflammatory bowel disease.
| S-EPMC3869396 | biostudies-literature
Project description:Purpose of reviewMulti-target stool DNA (MT-sDNA) was approved in 2014 for use in screening average-risk patients for colorectal cancer (CRC). Here, we highlight recent literature from post-market studies to provide an update on clinical use and utility not possible from pre-approval studies.Recent findingsMT-sDNA has been included in major society guidelines as an option for colorectal cancer screening, and has seen exponentially increasing use in clinical practice. MT-sDNA appears to be attracting new patients to CRC screening, and patient adherence to diagnostic colonoscopy after a positive MT-sDNA test is high. Approximately two-thirds of these patients are found to have colorectal neoplasia (CRN), 80% of whom have at least one right-sided lesion; 1 in 3 will have advanced CRN. High yield of CRN is due not only to post-screening increase in probability but also likely improved endoscopist attention. In those with a negative high-quality colonoscopy after positive MT-sDNA test ("false positive MT-sDNA"), further interventions do not appear to be necessary.SummaryMT-sDNA is a promising tool to improve rates and quality of CRC screening. Further investigation should examine MT-sDNA performance in populations at increased risk for CRC, and as an interval test after colonoscopy to detect potentially missed lesions.
| S-EPMC10966619 | biostudies-literature
Project description:ImportanceAlthough colonoscopy is frequently performed in the United States, there is limited evidence to support threshold values for physician adenoma detection rate as a quality metric.ObjectiveTo evaluate the association between physician adenoma detection rate values and risks of postcolonoscopy colorectal cancer and related deaths.Design, setting, and participantsRetrospective cohort study in 3 large integrated health care systems (Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Kaiser Permanente Washington) with 43 endoscopy centers, 383 eligible physicians, and 735 396 patients aged 50 to 75 years who received a colonoscopy that did not detect cancer (negative colonoscopy) between January 2011 and June 2017, with patient follow-up through December 2017.ExposuresThe adenoma detection rate of each patient's physician based on screening examinations in the calendar year prior to the patient's negative colonoscopy. Adenoma detection rate was defined as a continuous variable in statistical analyses and was also dichotomized as at or above vs below the median for descriptive analyses.Main outcomes and measuresThe primary outcome (postcolonoscopy colorectal cancer) was tumor registry-verified colorectal adenocarcinoma diagnosed at least 6 months after any negative colonoscopy (all indications). The secondary outcomes included death from postcolonoscopy colorectal cancer.ResultsAmong 735 396 patients who had 852 624 negative colonoscopies, 440 352 (51.6%) were performed on female patients, median patient age was 61.4 years (IQR, 55.5-67.2 years), median follow-up per patient was 3.25 years (IQR, 1.56-5.01 years), and there were 619 postcolonoscopy colorectal cancers and 36 related deaths during more than 2.4 million person-years of follow-up. The patients of physicians with higher adenoma detection rates had significantly lower risks for postcolonoscopy colorectal cancer (hazard ratio [HR], 0.97 per 1% absolute adenoma detection rate increase [95% CI, 0.96-0.98]) and death from postcolonoscopy colorectal cancer (HR, 0.95 per 1% absolute adenoma detection rate increase [95% CI, 0.92-0.99]) across a broad range of adenoma detection rate values, with no interaction by sex (P value for interaction = .18). Compared with adenoma detection rates below the median of 28.3%, detection rates at or above the median were significantly associated with a lower risk of postcolonoscopy colorectal cancer (1.79 vs 3.10 cases per 10 000 person-years; absolute difference in 7-year risk, -12.2 per 10 000 negative colonoscopies [95% CI, -10.3 to -13.4]; HR, 0.61 [95% CI, 0.52-0.73]) and related deaths (0.05 vs 0.22 cases per 10 000 person-years; absolute difference in 7-year risk, -1.2 per 10 000 negative colonoscopies [95%, CI, -0.80 to -1.69]; HR, 0.26 [95% CI, 0.11-0.65]).Conclusions and relevanceWithin 3 large community-based settings, colonoscopies by physicians with higher adenoma detection rates were significantly associated with lower risks of postcolonoscopy colorectal cancer across a broad range of adenoma detection rate values. These findings may help inform recommended targets for colonoscopy quality measures.
| S-EPMC9175074 | biostudies-literature
Project description:Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings.Prevention relevanceUnderstanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.
| S-EPMC9900315 | biostudies-literature
Project description:Background & aimsSeveral noninvasive tests have been developed for colorectal cancer (CRC) screening. We compared the sensitivities of a multimarker test for stool DNA (sDNA) and a plasma test for methylated septin 9 (SEPT9) in identifying patients with large adenomas or CRC.MethodsWe analyzed paired stool and plasma samples from 30 patients with CRC and 22 with large adenomas from Mayo Clinic archives. Stool (n = 46) and plasma (n = 49) samples from age- and sex-matched patients with normal colonoscopy results were used as controls. The sDNA test is an assay for methylated BMP3, NDRG4, vimentin, and TFPI2; mutant KRAS; the β-actin gene, and quantity of hemoglobin (by the porphyrin method). It was performed blindly at Exact Sciences (Madison, Wisconsin); the test for SEPT9 was performed at ARUP Laboratories (Salt Lake City, Utah). Results were considered positive based on the manufacturer's specificity cutoff values of 90% and 89%, respectively.ResultsThe sDNA test detected adenomas (median, 2 cm; range, 1-5 cm) with 82% sensitivity (95% confidence interval [CI], 60%-95%); SEPT9 had 14% sensitivity (95% CI, 3%-35%; P = .0001). The sDNA test identified patients with CRC with 87% sensitivity (95% CI, 69%-96%); SEPT9 had 60% sensitivity (95% CI, 41%-77%; P = .046). The sDNA test identified patients with stage I-III CRC with 91% sensitivity (95% CI, 71%-99%); SEPT9 had 50% sensitivity (95% CI, 28%-72%; P = .013); for stage IV CRC, sensitivity values were 75% (95% CI, 35%-97%) and 88% (95% CI, 47%-100%), respectively (P = .56). False positive rates were 7% for the sDNA test and 27% for SEPT9.ConclusionsBased on analyses of paired samples, the sDNA test detects nonmetastatic CRC and large adenomas with significantly greater levels of sensitivity than the SEPT9 test. These findings might be used to modify approaches for CRC prevention and early detection.
| S-EPMC3980432 | biostudies-literature
Project description:BackgroundColoDefense1.0 assay has demonstrated its excellent sensitivity and specificity for early detection of colorectal cancer (CRC) by detecting the methylation levels of SDC2 and SEPT9, while exhibited limitations on relatively large sample capacity required and limited detection throughput by applying triplicate PCR reactions for each sample. In this study, ColoDefense1.0 was simplified and optimized into ColoDefense2.0 in a single PCR reaction.MethodsA total 529 stool specimens were collected, and 244 CRC patients, 34 patients with advanced adenomas (AA), 64 with small polyps (SP) and 187 control subjects were divided in training and validation cohorts. Methylation levels of SEPT9 and SDC2 were examined by qPCR reactions in triplicate or single.ResultsThe stool DNA quantity stored in preservative buffer at 37 °C up to 7 days exhibited no significant decrease. In the training cohort, when the number of replicates reduced from 3 to 1, the overall performance of ColoDefense2.0 was identical to that of ColoDefense1.0, showing sensitivities of 71.4% for AA and 90.8% for all stage CRC with a specificity of 92.9%. In the validation cohort, sensitivities of SP, AA and CRC using ColoDefense2.0 were 25.0%, 55.0% and 88.2%, increased from 14.1% (20.3%), 40.0% (40.0%) and 79.4% (67.6%) using SDC2 (SEPT9) alone; along with an overall specificity of 90.2%, decreased from 94.1% (95.1%) using SDC2 (SEPT9) alone.ConclusionThe simplified ColoDefense test maintained the overall performance while reduced the number of PCR reactions to 1/3, and provided an effective and convenient tool to detect early CRC and precancerous lesions and potentially improve the compliance of screening.
| S-EPMC9540293 | biostudies-literature
Project description:Introduction:Population-level screening has been shown to reduce the incidence and mortality of colorectal cancer (CRC). Unfortunately, adherence to screening recommendations among eligible US adults remains below national goals. A relatively new non-invasive screening modality, the Food and Drug Administration-approved multi-target stool DNA (mt-sDNA) assay (commercialised as Cologuard), which combines the detection of haemoglobin and DNA abnormalities, has been completed by more than 3?million individuals. Given mt-sDNA's recent availability, the effectiveness of mt-sDNA screening with respect to CRC incidence and mortality reduction has not yet been established. Methods and analysis:Through an academic-industry collaboration, a prospective cohort study (Voyage) was designed with an initial enrolment target of 150?000 individuals with mt-sDNA ordered by their healthcare provider for CRC screening. Consented participants will be asked to complete a baseline questionnaire to collect sociodemographic and health information. Additional questionnaires will be provided after 1?year, and every 3?years thereafter, to collect data regarding CRC screening follow-up in order to estimate rates of CRC incidence and other health outcomes. Linkage to the National Death Index will be used to estimate mortality rates. Ethics and dissemination:The Voyage study will be conducted in accordance with international guidelines and local regulatory requirements and laws. Data will be stored and retained at Mayo Clinic. Only limited data elements required for research purposes will be transmitted between Mayo Clinic and Exact Sciences Laboratories. Results of the Voyage study will be disseminated through scientific presentations and publications. Trial registration number:NCT04124406.
| S-EPMC7039604 | biostudies-literature
Project description:Colorectal cancer screening dates to the discovery of precancerous adenomatous tissue. Screening modalities and guidelines directed at prevention and early detection have evolved and resulted in a significant decrease in the prevalence and mortality of colorectal cancer via direct visualization or using specific markers. Despite continued efforts and an overall reduction in deaths attributed to colorectal cancer over the last 25 years, colorectal cancer remains one of the most common causes of malignancy-associated deaths. In attempt to further reduce the prevalence of colorectal cancer and associated deaths, continued improvement in screening quality and adherence remains key. Noninvasive screening modalities are actively being explored. Identification of specific genetic alterations in the adenoma-cancer sequence allow for the study and development of noninvasive screening modalities beyond guaiac-based fecal occult blood testing which target specific alterations or a panel of alterations. The stool DNA test is the first noninvasive screening tool that targets both human hemoglobin and specific genetic alterations. In this review we discuss stool DNA and other commercially available noninvasive colorectal cancer screening modalities in addition to other targets which previously have been or are currently under study.
| S-EPMC4780449 | biostudies-other
Project description:Background and aimsPostcolonoscopy colorectal cancers (PCCRCs) are defined as those detected ≤10 years after an index colonoscopy negative for cancer, but modifiable risk factors are not well established in large, community-based populations.MethodsWe evaluated risk factors from the index colonoscopy for PCCRCs diagnosed 1 to 10 years after an index colonoscopy using a case-control design. Odds ratios (OR) and 95% confidence intervals (CI) were adjusted for potential confounders.ResultsA proximal polyp ≥10 mm (OR, 8.18; 95% CI, 4.59-14.60), distal polyp ≥10 mm (OR, 3.30; 95% CI, 1.65-6.58), adenoma with (OR, 3.23; 95% CI, 1.83-5.68) and without advanced histology (OR, 1.87; 95% CI, 1.37-2.55), and an incomplete colonoscopy (OR, 5.52; 95% CI, 2.98-10.21) were associated with PCCRC. Risk factors for early versus late cancers (12-36 months vs >36 months to 10 years after examination) included incomplete polyp excision in the colonic segment of the subsequent cancer (OR, 4.76; 95% CI, 2.35-9.65); failure to examine the segment (OR, 2.42; 95% CI, 1.27-4.60); and a polyp ≥10 mm in the segment (OR, 2.38; 95% CI, 1.53-3.70). A total of 559 of 1206 patients with PCCRC (46.4%) had 1 or more risk factors that were significant for PCCRC (incomplete examination, large polyp, or any adenoma).ConclusionsIn a large community-based study with comprehensive capture of PCCRCs, almost half of PCCRCs had potentially modifiable factors related to polyp surveillance or removal and examination completeness. These represent potential high-yield targets to further increase the effectiveness of colorectal cancer screening.
| S-EPMC7486003 | biostudies-literature
Project description:We have used a gene expression array-based strategy to identify the methylation of tissue factor pathway inhibitor 2 (TFPI2), a potential tumor suppressor gene, as a frequent event in human colorectal cancers (CRC). TFPI2 belongs to the recently described group of embryonic cell Polycomb group (PcG)-marked genes that may be predisposed to aberrant DNA methylation in early stages of colorectal carcinogenesis. Aberrant methylation of TFPI2 was detected in almost all CRC adenomas (97%, n = 56) and stages I to IV CRCs (99%, n = 115). We further explored the potential of TFPI2 as a biomarker for the early detection of CRC using stool DNA-based assays in patients with nonmetastatic CRC and average-risk noncancer controls who were candidates for screening. TFPI2 methylation was detected in stool DNA from stage I to III CRC patients with a sensitivity of 76% to 89% and a specificity of 79% to 93%. Detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of CRCs in the future.
| S-EPMC3062162 | biostudies-literature