Inappropriate Multi-Target Stool DNA Use for Colorectal Cancer Screening: Risks, Compliance, and Outcomes.

Background Inappropriate or "off-label" use of multi-target stool DNA (mt-sDNA) tests refers to their use in patients for whom colonoscopy or no testing at all is warranted. Examples include a positive family history of colorectal cancer, a history of inflammatory bowel disease, or medical issues necessitating diagnostic colonoscopy, among others. Current understanding of off-label mt-sDNA use for colorectal cancer screening, its associated risks, and outcomes is lacking. We examined off-label mt-sDNA prescription and compliance with testing in an outpatient setting in southeast Michigan. Aims The primary aims of the study were determining the extent of off-label mt-sDNA testing and compliance, and results of all testing, as well as demographic factors associated with off-label prescriptions. The secondary aims were to examine explanations for incomplete testing and factors contributing to successful completion. Methods Using a retrospective design, we identified mt-sDNA orders from outpatient internal medicine clinics between January 1, 2018, to July 31, 2019, to evaluate the proportion of off-label mt-sDNA, results of testing, and follow-up colonoscopies up to one year after order placement. Patients were categorized as "off-label" if any inappropriate criteria were met. Statistical analysis was performed for primary and secondary outcomes. Results From 679 mt-sDNA orders within the study period, 81 (12.1%) had at least one off-label criterion for testing. In total, 404/679 (59.5%) patients completed testing. Lack of follow-up comprised the majority of incompletions (216/275; 78.6%). Only 52 (70.3%) out of 74 positive results were followed by diagnostic colonoscopy. Retired employment status (OR = 1.87; 95%CI, 1.17-2.98; P = 0.008) and age of 76 years or older (OR = 2.28; 95%CI, 0.99-5.21; P = 0.044) were significantly associated with increased risk of off-label mt-sDNA prescription. Increasing age range was associated with higher test completion (χ2 (5) = 12.085, p = 0.034). Multinomial logistic regression revealed an increasing age range (OR = 1.29; 95% CI, 1.09-1.54; P = 0.004), predictive of a positive mt-sDNA result for both groups. There was no significant difference between off-label or on-label groups in the mean number of resected polyps or pathology scores on follow-up colonoscopy. Conclusions Off-label mt-sDNA use remains a concern in the outpatient setting. Compliance for test completion and follow-up colonoscopy for positive results require further improvement. Our findings shed new light on the factors associated with off-label testing while reiterating its burden. We also describe common reasons for incomplete tests in an attempt to augment future colorectal cancer (CRC) screening initiatives.

Healthcare costs, resource utilization, and productivity loss associated with colorectal cancer screening.

OBJECTIVES: To evaluate healthcare costs, resource utilization, associated costs, and lost productivity for colorectal cancer (CRC) screening in an average-risk population. METHODS: This retrospective cohort study identified average-risk individuals (50-75 years) with claims in the Optum Research Database for CRC screening test between 1 January 2014 to 31 December 2018. Index date was defined as the first date of a claim for colonoscopy, fecal immunochemical test (FIT), guaiac-based fecal occult blood test (FOBT) or multi-target stool DNA test (mt-sDNA). Screening costs were evaluated with descriptive statistics and multivariable analyses, adjusting for patient characteristics and index screening costs. RESULTS: In total, 903,831 individuals were identified by test groups: mt-sDNA (n = 29,614), FIT (n = 254,002), guaiac-based FOBT (n = 112,757) and colonoscopy (n = 507,458). Adjusted costs for index screening were, colonoscopy ($3,029), mt-sDNA ($752), FIT ($45), and (FOBT ($153). Adjusted costs across the six months following the index screening were $146 for colonoscopy, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. CONCLUSIONS: Screening colonoscopy had the highest productivity loss and healthcare costs up-front, suggesting potential cost benefits for noninvasive screening modalities. The more frequent screening interval required for FIT and FOBT resulted in a higher yearly cost than colonoscopy or mt-sDNA.

Colorectal cancer (CRC) is a prominent healthcare concern the United States, which accounted for 149,500 new cases and 52,980 deaths in 2021. Screening is effective for diagnosing the condition at earlier more treatable stages, and reducing deaths. However, screening is largely underutilized in part due to perceived cost barriers. This observational study used insurance claims data to calculate healthcare costs, resource use, and lost productivity for CRC screening in an average-risk population aged 50­75 years. A total of 903,831 individuals were identified by test groups: multi-target stool DNA test (mt-sDNA test; 29,614 individuals), fecal immunochemical test (FIT; 254,002 individuals), guaiac-based fecal occult blood test (FOBT; 112,757 individuals) and colonoscopy (507,458 individuals). Adjusted costs for initial screening were $3,029 for colonoscopy, $752 for mt-sDNA, $45 for FIT, and $153 for FOBT. Adjusted colonoscopy-related costs combined across the six months following the initial screening were $146 for the colonoscopy cohort, $329 for mt-sDNA, $306 for FIT, and $412 for FOBT. Colonoscopy had the highest costs for lost productivity. Overall, screening colonoscopy was accompanied by the highest productivity loss and up-front costs, suggesting potential cost benefits for noninvasive screening modalities ­ mt-sDNA, FIT, and FOBT; however, the more frequent screening interval required by FIT and FOBT resulted in a higher estimated average yearly screening cost.

Colorectal cancer screening: A review of current screening options, timing, and guidelines.

Screening for colon and rectal cancer has been associated with reduced incidence over the past few decades. However, shown a paradoxical increase in colon and rectal cancer in those younger than 50 years has also been recently shown. This information, along with the introduction of new screening modalities, has lead to updates in the current recommendations. We present some of the data supporting the use of current screening modalities, as well as summarize current guidelines.

Retrospective Review of Multitarget Stool DNA as a Screening Test for Colorectal Cancer.

OBJECTIVES: To review the effectiveness of noninvasive multitarget stool DNA testing as a screening test for colorectal cancer. METHODS: We performed a retrospective review of patients referred to 2 high volume outpatient procedural centers for colonoscopy for positive Cologuard test. Positive findings for colorectal cancer based on pathologic findings and also advanced adenomas were recorded. Positive predictive value (PPV) was assessed. RESULTS: Of the 1585 patients evaluated and referred for colonoscopy from January 1, 2018 to November 1, 2019, for ICD-10 codes R19.5 (other fecal abnormalities) and K92.1 (melena), 84 were referred for a positive Cologuard test. Out of the 84, 6 were excluded based on family history of colon cancer in first degree relative or personal history of inflammatory bowel disease. Of the remaining 78 patients, 1 patient (1.3%) had colorectal cancer and 5 (6.4%) had advanced adenomas (>1 cm size, high grade dysplasia or villous). Postive predictive value for colorectal cancer was 1.3% and for precancerous lesions plus colorectal cancer was 7.7%. A total of 53 (68.0%) patients had either totally normal colonoscopy or hyperplastic polyps. Out of the 78 individuals in our study, 70 (89.7%) had normal findings, hyperplastic polyps, or non-advanced adenomas. CONCLUSIONS: Multitarget stool DNA testing carries an unacceptably low PPV to be utilized as a screening test for colorectal cancer. The study fails to detect both adenomas and colon cancer at a higher rate than screening colonoscopy in selected studies. The advantage of being noninvasive has been noted to increase colorectal cancer screening in otherwise non-compliant Medicare patients.

Factors associated with colorectal cancer screening adherence and the impact of COVID-19 on screening patterns in Connecticut, USA.

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. Many communities remain under the 80% CRC screening goal. We aimed to identify factors associated with non-adherence to CRC screening and to describe the effect of the COVID-19 pandemic in CRC screening patterns. A retrospective review of patients aged 50-75 years seen at the Griffin Faculty Physicians primary care offices between January 2019 and December 2020 was performed. Logistic regression models were used to identify factors associated with CRC screening non-adherence. Of 12,189 patients, 66.2% had an updated CRC screen. On univariable logistic regression, factors associated with CRC screening non-adherence included age ≤ 55 years [odds ratio (OR) 2.267, p < 0.001], White/Caucasian race (OR 0.858, p = 0.030), Medicaid insurance (OR 2.097, p < 0.001), morbid obesity (OR 1.436, p < 0.001), current cigarette smoking (OR 1.849, p < 0.001), and elevated HbA1c (OR 1.178, p = 0.004). Age, Medicaid insurance, morbid obesity, current smoking, and HbA1c ≥ 6.5% remained significant in the final multivariable model. Compared to 2019, there was an 18.2% decrease in the total number of CRC screening tests in 2020. The proportion of colonoscopy procedures was lower in 2020 compared to the proportion of colonoscopy procedures conducted in 2019 (65.9% vs 81.7%, p < 0.001), with a concurrent increase in stool-based tests. CRC screening rates in our population are comparable to national statistics but below the 80% goal. COVID-19 affected CRC screening. Our results underscore the need to identify patient groups most vulnerable to missing CRC screening and highlight the importance of stool-based testing to bridge screening gaps.

Predictors of screening for cervical and colorectal cancer in women 50-65 years old in a multi-ethnic population.

Middle Eastern/North Africa (MENA) women are often not identified in cancer screening studies. The aim of this study was to determine the rates and predictors of cervical and colorectal cancer (CRC) screening for women 50-65 years of three race/ethnicities. White, black and MENA women of Southeast Michigan were surveyed once in 2019 for demographics, health care barriers, chronic diseases, and cancer screening updates using in-person, telephone, and online methods. Descriptive statistics and multivariate multinomial logistic regression were used to predict up-to-date colorectal cancer and cervical cancer screening. All analyses were adjusted by local population weights for comparability and generalizability. 394 women participated with 54% up-to-date on both screenings, 21% for cervical cancer screening alone, and 12% for CRC alone. Women more likely to be up-to-date for only cervical cancer screening compared to both cancer screens are younger (aOR 0.83 (95% CI 0.76, 0.92), are of MENA descent (7.97 (2.46, 25.76) and have no insurance (9.41 (1.07, 82.92). There are no predictors for women being up-to-date for CRC screening alone compared to both screens. Among women 50-65 years old, being up-to-date in cervical cancer screening is unrelated to being up-to-date for CRC screening. Compared to Healthy People 2020, there are significant gaps in cervical and CRC screening among women 50-65 years old of all races, but particularly among women of MENA descent who are even less likely to have CRC screening than cervical cancer screening.

Cross-sectional adherence with the multi-target stool DNA test for colorectal cancer screening: Real-world data from a large cohort of older adults.

OBJECTIVE: To determine cross-sectional adherence with the multi-target stool DNA test used for colorectal cancer screening in a large, fully insured Medicare population. METHODS: All patients aged 65-85 with a valid multi-target stool DNA test order from 1 September 2016 to 31 August 2017 identified from the Exact Sciences Laboratories (Madison, WI; sole-source national multi-target stool DNA test provider) database were evaluated for test adherence. Cross-sectional adherence, defined as multi-target stool DNA test completion within 365 days from order date, was analyzed overall and by time to adherence, as well as by available patient (age, sex, test order date, Medicare coverage type) and provider (specialty, year of first multi-target stool DNA test order, multi-target stool DNA test order frequency, and practice location) factors. RESULTS: Among 368,494 Medicare beneficiaries (64% female), overall cross-sectional adherence was 71%. Cumulative adherence rates increased more rapidly at 30 (44%) and 60 (65%) days, followed by more gradual increases at 90 (67%), 180 (70%), and 365 (71%) days. By provider specialty, primary care clinicians represented a higher percentage of multi-target stool DNA orders than gastroenterologists (88% vs. 6%), but had a lower associated patient adherence rate (71% vs. 78%). CONCLUSIONS: In this large, national sample of Medicare insured older adults, nearly three-quarters of patients adhered with a multi-target stool DNA order for colorectal cancer screening. These real-world data should inform further clinical and population health applications, reimbursement model simulations, and guideline-endorsed colorectal cancer screening strategies adherence.

Faecal tests in the early detection of colorectal cancer.

Colorectal cancer is one of the most common cancers in the world. It is the second most common cause of cancer deaths in both genders in Poland. Screening tests allow for early cancer detection, resulting in reduced mortality and better prognosis. Tests include a stool test for occult blood, checking for biomarkers in faeces, and stool DNA testing. Colonoscopy remains the gold standard in the diagnosis of cancer, both in Poland and around the world. To convince patients of the importance of such testing, it is necessary to have a wider knowledge of all the available diagnostic tests, to understand their advantages and disadvantages. This article will give descriptions of the respective tests and compare their effectiveness in the diagnosis of colorectal cancer.

Alaska Native Patient and Provider Perspectives on the Multitarget Stool DNA Test Compared With Colonoscopy for Colorectal Cancer Screening.

Objective: Alaska Native (AN) people have among the world's highest rate of colorectal cancer (CRC). We assessed perceptions of AN people and their health care providers of a new take-home multitarget stool DNA test (MT-sDNA; Cologuard) relative to colonoscopy. Methods: Cross-sectional surveys of AN people aged 40 to 75 years (mailed) and providers (online). Results: Participants included 1616 AN patients (19% response rate) and 87 providers (26% response rate; 57% AN people). Over half (58%) of patients preferred colonoscopy for CRC screening, while 36% preferred MT-sDNA. Unscreened patients were significantly more likely to state a preference for MT-sDNA than previously screened patients (42% vs 31%, P < .05) as were younger patients (<60 years old) compared with older patients (40% vs 30%, P < .05). Most providers thought that MT-sDNA would improve screening rates (69%), would recommend if available (79%), and be implementable (79%). Perceived barriers differed substantially between patients and providers in both type and magnitude. Leading colonoscopy barriers reported by patients were travel (44%) and bowel preparation (40%), while providers thought that fear of pain (92%) and invasiveness of the test (87%) were the primary barriers. For MT-sDNA, patients' belief that colonoscopy was better (56%) and not knowing how to do the test (40%) were primary barriers, while providers thought stool collection (67%) and having a stool sample in their home (63%) were leading barriers. Conclusions: This study found that MT-sDNA has potential acceptability among AN people and their health care providers. Both groups reported a willingness to use MT-sDNA and did not perceive major barriers to its use. This preference was especially true of unscreened and younger patients. The majority of providers indicated they would use MT-sDNA if available and that it would improve CRC screening rates. In this population, where colonoscopy access is limited, MT-sDNA has the potential to improve CRC screening adherence.

Molecular stool testing as an alternative for surveillance colonoscopy: a cross-sectional cohort study.

BACKGROUND: As in many other European countries, a nationwide screening program for colorectal cancer (CRC) has recently been introduced in the Netherlands. As a side effect, such a screening program will inherently yield an increase in the demand for surveillance after removal of polyps/adenomas or CRC. Although these patients are at increased risk of metachronous colorectal neoplasia, solid evidence on CRC-related mortality reduction as a result of colonoscopy-based surveillance programs is lacking. Furthermore, colonoscopy-based surveillance leads to high patient burden, high logistic demands and high costs. Therefore, new surveillance strategies are needed. The aim of the present study, named Molecular stool testing for Colorectal CAncer Surveillance (MOCCAS), is to determine the performance characteristics of two established non-invasive tests, i.e., the multitarget stool DNA test Cologuard® and the faecal immunochemical test (FIT) in the detection of CRC and advanced adenomas as an alternative for colonoscopy surveillance. METHODS: In this observational cross-sectional cohort study, subjects aged 50 to 75 years will be approached to collect (whole-) stool samples for molecular testing and a FIT prior to their scheduled surveillance colonoscopy. The results of the tests will allow calculation of test sensitivities and specificities in the context of surveillance. This will provide the required input for the Dutch ASCCA model (Adenoma and Serrated pathway to Colorectal CAncer) to simulate surveillance strategies differing in frequency and duration. The model will allow predictions of lifetime health effects and costs. Multiple centres in the Netherlands will participate in the study that aims to include 4,000 individuals. DISCUSSION: The outcome of this study will inform on the (cost-) effectiveness of stool based molecular testing as an alternative for colonoscopy in the rapidly expanding surveillance population. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT02715141 . Retrospectively registered 17 February 2016.

Fecal DNA testing for colorectal cancer screening: Molecular targets and perspectives.

The early detection of colorectal cancer with effective screening is essential for reduction of cancer-specific mortality. The addition of fecal DNA testing in the armamentarium of screening methods already in clinical use launches a new era in the noninvasive part of colorectal cancer screening and emanates from a large number of previous and ongoing clinical investigations and technological advancements. In this review, we discuss the molecular rational and most important genetic alterations hallmarking the early colorectal carcinogenesis process. Also, representative DNA targets-markers and key aspects of their testing at the clinical level in comparison or/and association with other screening methods are described. Finally, a critical view of the strengths and limitations of fecal DNA tests is provided, along with anticipated barriers and suggestions for further exploitation of their use.

Exact Sciences' experience with the FDA and CMS parallel review program.

Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the second leading cause of cancer death among men and women combined in the USA. Although the benefits of early CRC detection are widely recognized, screening rates are suboptimal. Cologuard is a multitarget stool DNA screening test that offers a unique non-invasive option for CRC screening. Cologuard was the first product to be reviewed under a pilot parallel review program jointly conducted by the US FDA and the Centers for Medicare & Medicaid Services (CMS). This parallel review process shortened the overall review for Cologuard and resulted in a preliminary National Coverage Determination that coincided with FDA approval.