Multitarget Stool DNA Test Research Articles

Next-Generation Multitarget Stool DNA vs Fecal Immunochemical Test in Colorectal Cancer Screening

This diagnostic study compares the specificity and sensitivity of comercial fecal immunochemical tests with a multitarget stool DNA test.

Is the Multitarget Stool DNA Test Just a Better “FIT” for Colorectal Cancer Screening?

Is the Multitarget Stool DNA Test Just a Better “FIT” for Colorectal Cancer Screening?

Adopting Non-invasive Approaches into Precision Colorectal Cancer Screening.

Effective screening is essential to reducing CRC incidence and mortality by detecting the disease at early stages and identifying non-invasive precursors. While colonoscopy remains the most sensitive modality to visualize and remove neoplastic lesions thereby reducing CRC and the related death, its high cost and invasive nature limit its widespread use. The fecal immunochemical test (FIT), which offers a non-invasive alternative with higher public acceptance and comparable cost-effectiveness to colonoscopy, has become the preferred screening method in many regions. Newer non-invasive tests, such as multitarget stool DNA or RNA tests, have shown improved sensitivity for CRC and advanced adenomas, although their high costs and lower specificity present challenges for large-scale implementation. Blood-based circulating cell-free DNA test also offer promise but still require optimization to be cost-effective. The heterogeneity of the screening population further complicates the effectiveness of CRC screening programs. Variations in non-communicable disease risk factors, such as metabolic syndrome, lifestyle habits, and comorbidities, can significantly influence CRC risk and screening outcomes. Moreover, diverse screening behaviors, including inconsistent adherence to recommended screening intervals and the interchangeable use of different screening modalities, add complexity to achieving uniform effectiveness across populations. This variability underscores the need for personalized screening strategies that consider individual risk profiles and screening behaviors, as well as the application of cutting-edge technologies such as big data analytics, artificial intelligence, and digital twin approaches to evaluate its effectiveness. This article reviews the current CRC screening strategies, the advantages of non-invasive methods, and the potential of fecal hemoglobin concentration, to tailor screening intervals and improve risk stratification. It also discusses the emerging role of real-world data and advanced technologies in enhancing CRC screening accuracy and effectiveness, particularly in complex real-world scenarios where traditional methods may fall short. Before novel non-invasive approaches, such as ctDNA tests or polygenic risk scores, are validated and proven cost-effective, exploring the clinical utility of FIT and its quantitative measurement in both screening and surveillance by integrating real-world clinical big data seems a feasible direction for achieving sustained development in population screening.

The Utility of Multitarget Stool DNA Testing for Colorectal Cancer Screening After a Normal Colonoscopy.

Multitarget stool DNA (MT-sDNA) tests (here, Cologuard®) are currently used in average-risk patients as a primary method of screening for colorectal cancer. However, MT-sDNA testing has also been used in patients who previously underwent colonoscopy who wish to avoid repeat colonoscopy. Here, in a large primary care practice setting, our aim was to evaluate the diagnostic performance of MT-sDNA testing in patients with a previously normal colonoscopy. This retrospective cohort study included 5827 patients from 35 different primary locations in South Carolina. Patients aged 45 and above with a previously documented normal, high-quality colonoscopy prior to the MT-sDNA test date were included. High-risk patients and those with a previous negative MT-sDNA result were excluded. Of 5827 ordered MT-sDNA tests, 248 patients had a prior normal colonoscopy. The average time from initial colonoscopy to MT-sDNA testing was 7.3years. Of the 63 patients who had a positive MT-sDNA test, 41 patients (65%) completed follow-up colonoscopy and 40 patients had complete colonoscopy data. Of these 40 patients, 12 patients (30%) had advanced adenomas and none had colorectal cancer. Compared to patients without a previous colonoscopy, patients with prior colonoscopies had fewer adenomas of all types (1.6 vs 2.4) and fewer advanced adenomas (1.4 vs 2.0). Patients with a previously negative colonoscopy and subsequent positive MT-sDNA test were found to have a high rate of advanced adenomas on follow-up colonoscopy (30%). Thus, in patients with a previously negative colonoscopy, MT-sDNA testing may be a reasonable alternative screening option.

Diagnostic Accuracy of Multitarget Stool DNA Test for Colorectal Cancer Screening and Detecting in Thailand.

A multitarget stool DNA test offers high sensitivity and specificity for screening and detecting colorectal cancer (CRC) in Western populations. However, its accuracy in Asian people is not well known. This study aimed to examine the diagnostic performance of multitarget stool DNA tests in Thailand. A prospective cross-sectional study was conducted from January 2023 to November 2023 at a tertiary university hospital in Bangkok. The study included both asymptomatic and symptomatic patients who underwent stool DNA testing followed by colonoscopy. The multitarget stool DNA test targeted methylation statuses of SDC2, ADHFE1, and PPP2R5C genes. Sensitivity, specificity, and other diagnostic parameters were analyzed. A total of 274 patients (mean age 62.1 years, 60.6% female) were enrolled. CRC was diagnosed in 17.2% of participants and 6.2% had advanced adenomas. The multitarget stool DNA test demonstrated a sensitivity of 91.5% (95% CI: 79.6-97.6) and specificity of 90.3% (95% CI: 85.7-93.8) for CRC detection. Its sensitivity for detecting CRC did not differ between right-sided lesions (92.3%) and left-sided lesions (91.2%) (P=0.901). The sensitivity for detecting CRC lesions size less than 2 cm was significantly lower than for larger lesions (25% vs 91.7%, p<0.001). Notably, the test's sensitivity and specificity for advanced colorectal neoplasms/cancer were 75.0% (95% CI: 62.6-85.0) and 91.9% (95% CI: 87.4-95.2), respectively. Multitarget stool DNA testing is highly sensitive and specific for CRC detection in Thai individuals. This testing could represent as a viable non-invasive alternative to colonoscopy especially in settings where colonoscopy is less accessible or less accepted by patients.

S533 An Analysis of Factors Affecting Follow-Up Colonoscopy in Patients Using Multi-Target Stool DNA Tests: A Multi-Center Retrospective Review

S533 An Analysis of Factors Affecting Follow-Up Colonoscopy in Patients Using Multi-Target Stool DNA Tests: A Multi-Center Retrospective Review

S460 Non-Invasive Screening Tests for Colorectal Cancer: Analyzing the Performance of FIT and Multi-Target Stool DNA Test

S460 Non-Invasive Screening Tests for Colorectal Cancer: Analyzing the Performance of FIT and Multi-Target Stool DNA Test

S493 Success of Repeated Orders for Multi-target Stool DNA Testing in Clinical Practice

S493 Success of Repeated Orders for Multi-target Stool DNA Testing in Clinical Practice

S427 Cross-Sectional Adherence With the Multi-Target Stool DNA Test for Colorectal Cancer Screening Among Four Largest Payors in the Country

S427 Cross-Sectional Adherence With the Multi-Target Stool DNA Test for Colorectal Cancer Screening Among Four Largest Payors in the Country

S462 Long-Term Oncologic Outcomes in Patients With History of Non-Colorectal Cancer and Positive Multi-Target Stool DNA Test With Negative Diagnostic Colonoscopy for Advanced Colorectal Neoplasia

S462 Long-Term Oncologic Outcomes in Patients With History of Non-Colorectal Cancer and Positive Multi-Target Stool DNA Test With Negative Diagnostic Colonoscopy for Advanced Colorectal Neoplasia

S512 Impact of Spanish Language Outreach on Multi-Target Stool DNA Test Adherence in a Spanish-Speaking Population in a Federally Qualified Health Center

S512 Impact of Spanish Language Outreach on Multi-Target Stool DNA Test Adherence in a Spanish-Speaking Population in a Federally Qualified Health Center

S513 Impact of Spanish Language Patient Navigation on Multi-Target Stool DNA Test Adherence Among Spanish-Speaking Patient Population

S513 Impact of Spanish Language Patient Navigation on Multi-Target Stool DNA Test Adherence Among Spanish-Speaking Patient Population

S458 Impact of Personalized Patient Outreach on Multi-Target Stool DNA Test Adherence in a Large Colorectal Cancer Screening Population

S458 Impact of Personalized Patient Outreach on Multi-Target Stool DNA Test Adherence in a Large Colorectal Cancer Screening Population

Is Noninvasive Next-generation Multitarget Stool DNA Test Useful for Colon Cancer Screening?

Is Noninvasive Next-generation Multitarget Stool DNA Test Useful for Colon Cancer Screening?

Disparities in Rates of Multitarget Stool DNA Test Completion for Colorectal Cancer Screening.

The aim was to assess patient adherence to multitarget stool DNA testing as well as factors associated with adherence. In the United States, disparities in colorectal cancer screening exist along racial and socioeconomic lines. While some studies suggest that stool-based screening tests may help reduce the screening gap, the data for multitarget stool DNA testing is unclear. We conducted a single-center retrospective cohort study on multitarget stool DNA testing ordered between April 2020 and July 2021. We calculated the proportion of patients who completed testing and used multivariate logistic regression to identify covariates associated with test adherence. Among 797 patients ordered for multitarget stool DNA testing, 481 patients (60.4%) completed testing. Adherence rates by patient subgroups ranged from 35.8% to 78.1%. Higher test adherence was found in Asian patients (odds ratio 2.65, 95% CI 1.36-5.18) and those who previously completed colorectal cancer screening (OR 1.45, 95% CI 1.01-2.09), while Black patients (OR 0.58, 95% CI 0.39-0.87), patients with resident primary care physicians (OR 0.34, 95% CI 0.21-0.56), and patients contacted through an outreach program (OR 0.47, 95% CI 0.25-0.87) had lower adherence. A significant proportion of patients ordered for multitarget stool DNA testing did not complete testing. Differences in adherence rates among patient subgroups may be reflective of underlying disparities in health care access.

Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The MOCCAS Study.

Colonoscopy-based surveillance to prevent colorectal cancer (CRC) causes substantial burden for patients and health care. Stool tests may help to reduce surveillance colonoscopies by limiting colonoscopies to individuals at increased risk of advanced neoplasia. This cross-sectional observational study included individuals aged 50-75 years with surveillance indication. Before bowel preparation, participants collected samples for a multitarget stool DNA test and 2 fecal immunochemical tests (FITs). Test accuracy was calculated for all surveillance indications. For the post-polypectomy indication only, which is the most common and is associated with a relatively low CRC risk, long-term impact of stool-based surveillance was evaluated with the Adenoma and Serrated Pathway to Colorectal Cancer (ASCCA) model. Stool-based strategies were simulated to tune each test's positivity threshold to obtain strategies at least as effective as colonoscopy surveillance. There were 3453 individuals with results for all stool tests and colonoscopy; 2226 had previous polypectomy, 1003 had previous CRC, and 224 had a familial risk. Areas under the receiver operating characteristic curve for advanced neoplasia were 0.72 (95% CI, 0.69-0.75) for the multitarget stool DNA test, 0.61 (95% CI, 0.58-0.64) for the FIT OC-SENSOR (Eiken Chemical Co, Tokyo, Japan) and 0.59 (95% CI, 0.56-0.61) for the FIT FOB-Gold (Sentinel, Milan, Italy). Stool-based post-polypectomy surveillance strategies at least as effective as colonoscopy surveillance reduced the number of colonoscopies by 15%-41% and required 5.6-9.5 stool tests over a person's lifetime. Multitarget stool DNA-based surveillance was more costly than colonoscopy surveillance, whereas FIT-based surveillance saved costs. This study found that stool-based post-polypectomy surveillance strategies can be safe and cost-effective, with potential to reduce the number of colonoscopies by up to 41%. gov, Number: NCT02715141.

Population health outcomes of blood-based screening for colorectal cancer in comparison to current screening modalities: insights from a discrete-event simulation model incorporating longitudinal adherence

Aim Insufficient adherence to colorectal cancer (CRC) screening impedes individual and population health benefits, with about one-third of individuals non-adherent to available screening options. The impact of poor adherence is inadequately considered in most health economics models, limiting the evaluation of real-world population-level screening outcomes. This study introduces the CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model, utilizing real-world adherence scenarios to assess the effectiveness of a blood-based test (BBT) compared to existing strategies. Materials and methods The CAN-SCREEN model evaluates various CRC screening strategies per 1,000 screened individuals for ages 45–75. Adherence is modeled in two ways: (1) full adherence and (2) longitudinally declining adherence. BBT performance is based on recent pivotal trial data while existing strategies are informed using literature. The full adherence model is calibrated using previously published Cancer Intervention and Surveillance Modeling Network (CISNET) models. Outcomes, including life-years gained (LYG), CRC cases averted, CRC deaths averted, and colonoscopies, are compared to no screening. Results Longitudinal adherence modeling reveals differences in the relative ordering of health outcomes and resource utilization, as measured by the number of colonoscopies performed per 1,000, between screening modalities. BBT outperforms the fecal immunochemical test (FIT) and the multitarget stool DNA (mtsDNA) test with more CRC deaths averted (13) compared to FIT and mtsDNA (7, 11), more CRC cases averted (27 vs. 16, 22) and higher LYG (214 vs. 157, 199). BBT yields fewer CRC deaths averted compared to colonoscopy (13, 15) but requires fewer colonoscopies (1,053 vs. 1,928). Limitations Due to limited data, the CAN-SCREEN model with longitudinal adherence leverages evidence-informed assumptions for the natural history and real-world longitudinal adherence to screening. Conclusions The CAN-SCREEN model demonstrates that amongst non-invasive CRC screening strategies, those with higher adherence yield more favorable health outcomes as measured by CRC deaths averted, CRC cases averted, and LYG.

Patient-Provider Communication and Colorectal Cancer Screening Completion Using Multi-target Stool DNA Testing.

Colorectal cancer (CRC) screening continues to be underutilized in the USA despite the availability of multiple effective, guideline-recommended screening options. Provider recommendation has been consistently shown to improve screening completion. Understanding how patient-provider communication influences CRC screening can inform interventions to improve screening completion. We developed a behavioral theory-informed survey to identify patient-provider communication factors associated with multi-target stool DNA (mt-sDNA) screening completion. The survey was administered by RTI International between 03/2022 and 06/2022 to a sample of US adults ages 45-75 who received a valid order for mt-sDNA screening with a shipping date between 5/2021 and 9/2021. Respondents completed an electronic or paper survey. Multivariable logistic regression was used to identify patient-provider communication factors associated with mt-sDNA test completion. A total of 2973 participants completed the survey (response rate, 21.7%) and 81.6% of them (n = 2427) reported having had a conversation with provider about mt-sDNA testing before the test was ordered. Having a conversation with the provider about the test, including discussions about costs, the need for follow-up testing and test instructions were associated with higher odds of test completion and being "very likely" to use the test in the future. Lack of discussion about advantages and disadvantages of available CRC screening options and lack of patient involvement in CRC screening decision-making were associated with reduced odds of test completion and likelihood of future use. Healthcare providers play a key role in patient adherence to CRC screening and must be appropriately prepared and resourced to educate and to engage patients in shared decision-making about CRC screening.

Real-world multi-target stool DNA longitudinal adherence for colorectal cancer re-screening in a large, national population.

e15633 Background: Colorectal cancer (CRC) is the fourth most diagnosed cancer, as well as the second leading cause of cancer death in the United States – with an estimated 152,810 diagnoses and 53,010 fatal cases in 2024. Regular screening and early detection can reduce CRC incidence and improve overall survival; however, recent national survey data (2021) demonstrate that only 59% of the US screen-eligible population (≥ age 45) is up to date. Home-based, non-invasive CRC screening test options, such as the multi-target stool DNA (mt-sDNA) test, have the potential to improve patient outcomes and overcome CRC screening adherence barriers at multiple levels. Given that the recommended interval for mt-sDNA is three years, a better understanding of use in repeat users is warranted. We evaluated the effective rescreen rate of previous mt-sDNA test users. Methods: In this retrospective cohort study, we included patients between the ages of 45 and 75 years who were shipped an mt-sDNA test kit between January 1st – December 31st, 2023, and had previously completed mt-sDNA screening with a negative result &gt; 2.5 years prior. Our primary variable of interest was mt-sDNA completion rate on repeat testing, defined as kit receipt with a valid result within 120 days of the shipment date. Regression analysis was performed to determine baseline characteristics associated with repeat test completion rate. Results: During the analysis period, a total of 481,748 patients who met the inclusion criteria received an mt-sDNA kit. The majority of the cohort was female (61.4%) and between the ages of 65-75 years (50.9%). Overall repeat test completion rate was 83.6%, with the average time to kit return being 18.9 days. Completion rates were similar between males (83.8%) and females (83.6%), and patients receiving included navigation support via mobile phones demonstrated the shortest average time to kit return (18.7 days). Completion rates increased concordantly with patient age: 81.6%, (45-49 years), 82.2% (50-64 years), and 85% (65-75 years). For first-time rescreen participants (2nd lifetime mt-sDNA test), the completion rate was 83.1%. For second-time rescreen participants (3rd lifetime mt-sDNA test), the completion rate was even higher at 93.6%. Logistic regression analyses revealed that patients re-screening for a second-time were three times more likely to return the mt-sDNA kit for CRC screening (OR = 3.118; p &lt; 0.001). Conclusions: Data from this large, retrospective cohort study revealed that repeat CRC screening with the mt-sDNA test is associated with high adherence to triennial follow-up among participants. suggesting a high-level of perceived patient confidence in repeat performance of the mt-sDNA test. These novel data provide relevant insights regarding strong patient willingness to continue with home-based, non-invasive mt-sDNA testing over multiple cycles of average-risk CRC screening.

Real-world multi-target stool DNA adherence in an underserved and vulnerable prison patient population.

e15632 Background: In 2024, colorectal cancer (CRC) is estimated to be the fourth most diagnosed cancer, as well as the second leading cause of cancer death in the United States. While adherence to regular CRC screening has been suboptimal in the general population, this holds to be especially true in populations that are medically underserved. Non-invasive tests, such as the guideline recommended multi-target stool DNA (mt-sDNA) test, offer a more accessible option to increase screening participation in difficult to reach populations. Herein, we evaluated adherence to CRC screening in a cohort of prisoners who received the mt-sDNA test at a Nebraska Department of Corrections facility in Nebraska. Methods: This was a retrospective cohort study in a small prison population. Participants included both males and females between the ages of 45 and 75 years who underwent CRC screening evaluation at the prison’s medical center between June 1st – December 31st, 2023 and were offered multiple CRC screening options, including the mt-sDNA test. No inducements were provided for completion of the mt-sDNA test. Baseline demographics were collected for cohort description. The primary variable of interest was mt-sDNA test return rate (adherence), defined as completion of the mt-sDNA test within 60 days of kit receipt. We also evaluated mt-sDNA test results in secondary analyses. Results: Once inclusion criteria were applied, the resulting analysis cohort included 129 patients who were first time mt-sDNA screeners. The cohort was largely male (96.9%) and between the ages of 50-64 years (78.3%). Overall mt-sDNA test adherence was 95.3%, with the average time to test completion being 20 days. No significant difference was seen in test completion among males and females (95.2% vs 100%, respectively). Completion rates increased with patient age, at 90.9% (45-49 years), 95% (50-64 years), and 100% (65-75 years). The shortest time to completion in the population was observed amongst patients who were females (18.8 days), and those between the ages of 45-49 years (17.1 days). Negative and positive mt-sDNA test results were observed in 82.9% and 17.1% of the cohort, respectively. Conclusions: CRC screening with the mt-sDNA test in this single-center study of incarcerated participants yielded exceptionally high adherence rates within 60 days of kit receipt. Assessment of follow up colonoscopy rates for test-positive participants is ongoing. While based on a relatively small sample size in this initial study, the mt-sDNA test exhibited favorable completion rates in a difficult to reach population, supporting further efforts to characterize patient, provider, and system-level benefits that may be obtained through broader adoption of this highly accessible screening approach in this challenging healthcare setting.