Multitarget Stool DNA Test Research Articles

Specificity of the Multi-Target Stool DNA Test for Colorectal Cancer Screening in Average-Risk 45-49 Year-Olds: A Cross-Sectional Study.

High-specificity colorectal cancer screening is desirable to triage patients <50 years for colonoscopy; however, most endorsed colorectal cancer screening tests have not been rigorously evaluated in younger populations. This prospective cross-sectional study determined the specificity of the multitarget stool DNA (mt-sDNA) test in an average-risk screening population of 45 to 49 year-olds. Specificity was the primary outcome and was measured in participants without colorectal cancer or advanced precancerous lesions [APL- advanced adenomas (AA), and sessile serrated lesions ≥10 mm], and in the subgroup of participants with negative colonoscopic findings. APL sensitivity was a secondary outcome. The evaluable cohort included those who completed the study without protocol deviations and had a usable mt-sDNA test. Of 983 enrolled participants, 816 formed the evaluable cohort, with a mean age of 47.8 (SD, 1.5) years; 47.7% were women. No participants had colorectal cancer, 49 had APL, 253 had nonadvanced adenomas (NAA), and 514 had negative colonoscopic findings. mt-sDNA test specificity was 95.2% (95% CI, 93.4-96.6) in participants with NAA or negative findings [96.3% (confidence interval (CI), 94.3%-97.8%)] in those with negative findings, and did not differ by sex (P = 0.75) or race (P = 0.36) in participants with NAA or negative findings. Sensitivity for APL was 32.7% (CI, 19.9-47.5%), with most APL (83.7%) measuring 10-19 mm and none having high-grade dysplasia. The area under the ROC curve for discriminating between APL and lesser findings was 0.72 (CI, 0.64-0.81). mt-sDNA's high specificity would help minimize risk from unnecessary diagnostic procedures in this age group. This study shows that mt-sDNA has high specificity among average-risk 45 to 49-year olds, supporting its use as a noninvasive option for colorectal cancer screening. PREVENTION RELEVANCE: This study shows that mt-sDNA has high specificity among average-risk 45-49 year olds, supporting its use as a non-invasive option for colorectal cancer screening.

Barriers to Follow-Up Colonoscopy After Positive FIT or Multitarget Stool DNA Testing.

Fecal immunochemical testing (FIT) and multi-target stool DNA testing (mt-sDNA) are recommended colorectal cancer screening options but require follow-up with colonoscopy to determine the source of a positive result. We performed a retrospective analysis in an academic health system to determine adherence to colonoscopy in these patients. We identified all patients aged 40 years and older with at least 1 primary care visit who had a positive FIT or mt-sDNA between January 2016 and June 2018. We identified receipt of colonoscopy within 6 months of the positive test and reviewed medical records to determine reasons for lack of colonoscopy. We identified 308 eligible patients with positive FIT and 323 with positive mt-sDNA. Some patients with positive FIT (46.7%) and patients with positive mt-sDNA (71.5%) underwent colonoscopy within 6 months, and time to colonoscopy was also shorter with mt-sDNA (hazard ratio, 1.83; 95% CI, 1.48-2.25). These differences remained in a multivariable model adjusting for patient characteristics. Among patients without colonoscopy after positive FIT, 1 or more system, provider, and patient-related barriers were identified in 32.1%, 57.6%, and 36.3%, respectively. Among patients without colonoscopy after positive mt-sDNA, corresponding frequencies were 30.4%, 43.5%, and 57.6%, respectively. Follow-up colonoscopy was higher for mt-sDNA than FIT, which could be due in part to preselection by clinicians and/or patients. Among patients who did not follow-up, provider and system factors were as frequently encountered as patient factors. These findings reinforce the need for multi-level interventions to improve follow-up.

Evaluating Outreach Methods for Multi-Target Stool DNA Test for Colorectal Cancer Screening Among an Employer Population.

Introduction/Objectives:Despite compelling evidence of clinical and economic benefits, adherence to colorectal cancer (CRC) screening remains low. Increasing public awareness through various outreach methods may improve screening uptake. The objective of this study was to evaluate the uptake of non-invasive multi-target stool DNA (mt-sDNA) by different outreach methods in an average-risk employer population.Methods:This retrospective observational study included CRC screening-eligible individuals aged ≥50 years insured by the Metropolitan Nashville Public Schools (MNPS) employee healthcare plan. The study intervention arms included population-based outreach and office visit-based interaction. The mt-sDNA completion rate (proportion of individuals who return the mt-sDNA kit after consenting to have it shipped to their home), proportion of patients who performed follow-up colonoscopy after a positive test, and time to follow-up colonoscopy were assessed.Results:A total of 167 mt-sDNA kits were shipped to eligible participants (aged 50-64 years) in the population-based outreach arm. In the office visit-based interaction arm, a total of 132 mt-sDNA kits were shipped to eligible participants (aged ≥50 years). The mt-sDNA completion rate was significantly higher for office visit-based interaction as compared to population-based outreach (76.8% vs 53.5%; P < .001) among those aged 50 to 64 years. While all patients aged 50 to 64 years with a positive mt-sDNA result received a follow-up colonoscopy in both arms, the median time to follow-up colonoscopy was shorter among the population-based outreach (55 vs 136 days; P < .05).Conclusions:Office visit-based interaction was associated with a higher mt-sDNA completion rate as compared to the population-based outreach among average-risk, CRC screening-eligible individuals aged 50 to 64 years old.

The health economic impact of varying levels of adherence to colorectal screening on providers and payers

Aims To examine the impact of increasing multi-target stool DNA test (mt-sDNA [Cologuard]) utilization for colorectal cancer (CRC) screening in cohorts aged 50–75 and 45–75 years old with varying levels of adherence from the perspectives of integrated delivery networks (IDNs) and payers. Materials and methods We developed a budget impact model that simulates CRC screening with colonoscopy over a 10-year time horizon, fecal immunochemical test (FIT), and mt-sDNA according to the United States Preventive Services Task Force and American Cancer Society guidelines for average risk adults. We evaluated varying levels of screening adherence for a status quo scenario and for an increased mt-sDNA utilization scenario, from the IDN and payer perspectives. The IDN perspective included CRC screening program costs, whereas the payer perspective did not. Conversely, stool-based screening test and bowel preparation costs were unique to the payer perspective. Results The increased mt-sDNA scenarios yielded cost savings relative to the status quo under all adherence scenarios due to a decrease in screening and surveillance colonoscopies. For ages 50–75, in high and low adherence scenarios, savings were $19.8 M ($0.16 per-person-per-month (PPPM)) and $33.3 M ($0.28 PPPM) from the IDN perspective. From the payer perspective, savings were $4.2 M ($0.03 PPPM) and $6.7 M ($0.06 PPPM). For ages 45–75, in high and low adherence scenarios, cost savings were $19.3 M ($0.16 PPPM) and $33.0 M ($0.28 PPPM) from the IDN perspective and $3.9 M ($0.03 PPPM) and $6.2 M ($0.05 PPPM) from the payer perspective. In all imperfect adherence scenarios, the degree of cost-savings with increased mt-sDNA utilization correlated with the aggregate decrease in screening and surveillance colonoscopies. Limitations Estimates of real-world adherence levels were based on cross-sectional screening data from the literature, and assumptions were applied to individual screening modalities and screening scenarios. Conclusions Among all adherence scenarios, perspectives, and age ranges, increased mt-sDNA utilization yielded cost-savings.

Noninvasive strategies for colorectal cancer screening: opportunities and limitations.

In the United States, only 67% of patients are up to date with colorectal cancer (CRC) screening. While colonoscopy is highly sensitive and specific for CRC and precursor lesion detection and removal, it is invasive, expensive and resource heavy. Hence, there is an unfulfilled need for multiple modality CRC screening that can improve current CRC screening rates and may be resource effective strategies when used in conjunction with a colonoscopy program. Our review highlights the complementary, often underutilized, noninvasive CRC screening methods with a focus on performance, risks, benefits, and recent updates. Studies demonstrate that fecal immunochemical testing (FIT) is superior to guaiac-based fecal occult blood tests for CRC screening. Studies show superiority of multitarget stool DNA test to FIT in sensitivity, though with concern for decreased specificity in setting of one-time tests. Technical advances continue to improve accuracy of colon capsule endoscopy. There are ongoing studies to characterize often difficult-to-detect high-risk lesions in computed tomography colonography. Septin 9 continues to have suboptimal accuracy for CRC screening, but has been shown to be associated with more advanced, invasive CRC stages. There are ongoing advances in noninvasive screening modalities for CRC; these should be considered as alternatives to colonoscopy in specific patient populations.

Colorectal Cancer Screening With the Multitarget Stool DNA Test.

Colorectal Cancer Screening With the Multitarget Stool DNA Test.

S0279 Predicted Colorectal Cancer Outcomes With Reported Adherence to Follow-Up Colonoscopy After a Positive Stool-Based Test

INTRODUCTION: Colonoscopy (COL) non-adherence following a positive non-invasive colorectal cancer (CRC) screening test (e.g., multitarget stool DNA [mt-sDNA], fecal immunochemical test [FIT]) undermines the achievable benefits of screening. Given wide variations in the limited data reporting COL adherence after a positive non-invasive test, microsimulation modeling was used to estimate the clinical implications of this understudied input. METHODS: An average-risk US population cohort free of diagnosed CRC at age 40 that underwent triennial mt-sDNA or annual FIT screening from ages 50 to 75 was simulated using the validated CRC-AIM model. Three scenarios were modeled: (S1) assumed 100% adherence for initial screening and COL follow-up; (S2) reported adherence rates for initial mt-sDNA (71%) or FIT (43%) screening, with assumed 100% adherence to COL follow-up; and (S3) reported adherence rates for initial mt-sDNA or FIT screening and reported adherence rates for COL follow-up after positive mt-sDNA (73%) or FIT (47%). Sensitivity analyses were performed using 100% and reported adherence rates for mt-sDNA and FIT screening, with COL follow-up adherence ranging from 40%-100%. Patients without a COL follow-up were assumed to be non-adherent until CRC symptom onset. Outcomes for each scenario are per 1000 individuals. RESULTS: S1, S2, and S3 each yielded life-years gained (LYG) and reductions in CRC incidence and CRC mortality with either mt-sDNA or FIT screening vs no CRC screening (Table 1). Estimated LYG for mt-sDNA and FIT were 297 and 316 for S1, 284 and 245 for S2, and 203 and 113 for S3, respectively. Reductions in CRC incidence for mt-sDNA and FIT were 64% and 68% for S1, 61% and 50% for S2, and 43% and 23% for S3, respectively; reductions in CRC mortality were 72% and 76% for S1, 69% and 59% for S2, and 49% and 27% for S3, respectively. With assumed 100% adherence to mt-sDNA or FIT screening, the LYG transition was at 45% (LYG = 128) and 40% (LYG = 119) adherence for COL follow-up, respectively (Figure 1). At reported adherence for stool-tests, the additional LYG for mt-sDNA vs FIT ranged from 12 to 188 as follow-up COL adherence increased from 40% to 100% (Figure 2). CONCLUSION: These modeling analyses demonstrate that the inclusion of more realistic estimates for mt-sDNA, FIT, and COL follow-up adherence has substantial impact on the predicted outcomes. Using reported adherence rates, rather than assuming 100% adherence, mt-sDNA yields greater CRC screening benefits vs FIT.Table 1.: Predicted life-years gained (LYG), colorectal cancer (CRC) incidence reduction, and CRC mortality reduction for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) in 3 different adherence scenarios per 1000 individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 yearsFigure 1.: Percent difference in predicted life-years gained (LYG) per 1000 individuals assuming 100% adherence for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) at assumed adherence rate intervals for follow-up colonoscopy (COL) in individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 years. White boxes indicate 10% positive difference with mt-sDNA versus FIT. Dark gray boxes indicate >10% negative difference with mt-sDNA versus FIT.Figure 2.: Percent difference in predicted life-years gained (LYG) per 1000 individuals by reported adherence rates for triennial multitarget stool DNA (mt-sDNA) and annual fecal immunochemical test (FIT) at assumed adherence rate intervals for follow-up colonoscopy (COL) in individuals free of diagnosed colorectal cancer at age 40 and screened between 50–75 years. White boxes indicate 10% positive difference with mt-sDNA versus FIT. Dark gray boxes indicate >10% negative difference with mt-sDNA versus FIT.

S0306 A Team-Based Approach Is Effective in Improving Colorectal Cancer Screening Rates in a Community-Based Resident Clinic

INTRODUCTION: Colorectal cancer (CRC) is the second leading cause to cancer-related mortality. This has resulted in increased utilization of screening modalities including fecal immunochemical test (FIT), multi-target stool DNA test (MT-sDNA) and colonoscopy. In 2016, 67.2% of the US population who are 50–75 years old were up-to-date on their CRC screening. Comparatively, CRC screening rates at our academic Internal Medicine resident-based clinic were 42.5%. Therefore, we established a team-based approach to improve the CRC screening program at our community-based clinic. The aim was to achieve a 3% increase in screening rates over the year 2019 which aligns with our organization goal. METHODS: Institute of Healthcare model for improvement was used as a framework for this quality improvement project. Initially, a team was assembled, comprised of resident physicians, practice manager (PM) and patient navigators [nurses and medical assistants (MAs)]. Afterwards, a root-cause analysis was performed to identify contributing factors to our low CRC screening rates and explore areas for improvement (Figure 1). Interventions were implemented across three cycles of improvement (Figure 2). This comprised of providing appropriate CRC screening education to the providers and clinic staff. Personal dashboards were then distributed to residents with the list of patients due for screening from their own panel. This was followed by identification of patients due for CRC screening as part of pre-visit planning and during daily inter-professional staff huddles. Furthermore, an educational brochure comparing the different screening modalities was given to eligible patients by MAs prior to seeing the provider. Choice of a screening method was recommended by the provider based on the patient’s CRC risk. Screening tests results were closely tracked and updated by MAs. Patients with incomplete orders after 30 days were followed by a phone call conducted by a resident physician. CRC screening registry was updated on monthly basis by the PM. RESULTS: There was a steady increase in CRC screening rates from a pre-intervention median of 42.5% to 48.5% by the end of December, 2019. Using run chart rules, this change is significant for a positive shift (Figure 3). CONCLUSION: A team-based approach is an effective method to improve CRC screening rates in a resident-based clinic. We anticipate that our intervention will show more measurable outcomes in the future through continuous cycles of improvement.Figure 1.: Root-Cause Analysis for low CRC screening rates. Abbreviations: CRC-Colorectal Cancer, FIT-Fecal Immunochemical Test, MT-sDNA-Multitarget stool DNA, EMRs-Electronic Medical Records.Figure 2.: PDSA cycles of improvement. Abbreviations: PDSA- Plan-Do-Study-Act.Figure 3.: Run chart graph detailing the exact times for the interventions during the year 2019. A positive Shift can be seen by having six consecutive points above the pre-intervention median. Abbreviations: PDSA- Plan-Do-Study-Act **The red central line reflects the pre-intervention median for the values from June, 2018 to January, 2019.

S0284 Off-Label Use of the Multi-Target Stool DNA Test (Cologuard™) in Primary Care

S0284 Off-Label Use of the Multi-Target Stool DNA Test (Cologuard™) in Primary Care

S0280 Lowering the Colorectal Cancer Screening Age Improves Predicted Outcomes in Pre-Medicare and Medicare Populations in the CRC-AIM Microsimulation Model

INTRODUCTION: Most US guidelines recommend average risk colorectal cancer (CRC) screening for ages 50–75. An increasing CRC incidence among younger populations renders critical the need to evaluate the potential benefit of earlier CRC screening initiation. Using the validated CRC-AIM microsimulation model, we estimated the impact of lowering the CRC screening initiation age on outcomes for triennial multitarget stool DNA (mt-sDNA) or annual fecal immunochemical test (FIT) screening strategies. METHODS: Screening strategies were simulated for individuals free of diagnosed CRC at age 40 and screened from ages 50–75 or 45–75. CRC incidence, mortality, and life-years gained (LYG) were assessed for pre-Medicare eligible and Medicare eligible years (ages 65–75). Adherence rates were assumed to be as previously reported (71% for mt-sDNA vs 43% for FIT) or perfect (100%). Predicted outcomes of screening vs no screening are per 1000 individuals. Statistical differences between ages 45 and 50 were assessed by McNemar’s test. RESULTS: For individuals who initiated screening at age 45 with reported adherence, triennial mt-sDNA and annual FIT resulted in 23.9 and 24.4 more predicted LYG, respectively, versus starting screening at age 50 (Figure 1). With reported adherence, reductions in CRC incidence with mt-sDNA were 64.5% and 61.1% at screening start ages of 45 and 50, respectively, and with FIT were 53.7% and 49.9% (both P < 0.0001). Reductions in CRC mortality with mt-sDNA were 71.7% and 68.7% at screening start ages of 45 and 50, respectively, and with FIT were 62.7% and 59.0% (both P < 0.0001). Reductions in CRC cases and deaths were observed for both pre-Medicare and Medicare populations (Figures 2-3). With reported adherence, the number of CRC cases and deaths were lower with triennial mt-sDNA than annual FIT regardless of screening start age. Improvement in outcomes with earlier screening initiation were greater when assuming reported versus perfect adherence. CONCLUSION: Non-invasive stool-based screening tests may serve as effective early screening tools among younger populations. LYG and reductions in CRC incidence and mortality are greater when beginning screening at age 45 vs age 50, with gains applying to both pre-Medicare and Medicare populations. CRC outcomes were improved with a lower initiation age for both reported and perfect adherence model assumptions. When assuming reported adherence rates, mt-sDNA confers greater benefits than FIT.Figure 1.: Life-years gained (LYG) with triennial mt-sDNA and annual FIT assuming reported or perfect adherence and screening start ages of 45 or 50 years.Figure 2.: CRC cases per 1000 individuals with triennial mt-sDNA and annual FIT assuming reported or perfect adherence and screening start ages of 45 or 50 years. Results are shown for the pre-Medicare eligibility years (ages 45– or 50–64) or during Medicare eligibility (ages 65–75).Figure 3.: CRC deaths per 1000 individuals with triennial mt-sDNA and annual FIT assuming reported or perfect adherence and screening start ages of 45 or 50 years. Results are shown for the pre-Medicare eligibility years (ages 45– or 50–64) or during Medicare eligibility (ages 65–75).

S0283 A Single Center Review of Patients With a Positive Multi-Target Stool DNA Test and Negative Colonoscopy

S0283 A Single Center Review of Patients With a Positive Multi-Target Stool DNA Test and Negative Colonoscopy

Comparing the Cost-Effectiveness of Innovative Colorectal Cancer Screening Tests.

BackgroundColorectal cancer (CRC) screening with colonoscopy and the fecal immunochemical test (FIT) is underused. Innovative tests could increase screening acceptance. This study determined which of the available alternatives is most promising from a cost-effectiveness perspective.MethodsThe previously validated Microsimulation Screening Analysis-Colon model was used to evaluate the cost-effectiveness of screening with capsule endoscopy every 5 or 10 years, computed tomographic colonography every 5 years, the multi-target stool DNA test every 1 or 3 years, and the methylated SEPT9 DNA plasma assay (mSEPT9) every 1 or 2 years. We also compared these strategies with annual FIT screening and colonoscopy screening every 10 years. Quality-adjusted life-years gained (QALYG), number of colonoscopies, and incremental cost-effectiveness ratios were projected. We assumed a willingness-to-pay threshold of $100 000 per QALYG.ResultsAmong the alternative tests, computed tomographic colonography every 5 years, annual mSEPT9, and annual multi-target stool DNA screening had incremental cost-effectiveness ratios of $1092, $63 253, and $214 974 per QALYG, respectively. Other screening strategies were more costly and less effective than (a combination of) these 3. Under the assumption of perfect adherence, annual mSEPT9 screening resulted in more QALYG, CRC cases averted, and CRC deaths averted than annual FIT screening but led to a high rate of colonoscopy referral (51% after 3 years, 69% after 5 years). The alternative tests were not cost-effective compared with FIT and colonoscopy.ConclusionsThis study suggests that for individuals not willing to participate in FIT or colonoscopy screening, mSEPT9 is the test of choice if the high colonoscopy referral rate is acceptable to them.

COVID-19: An Opportunity to Reimagine Colorectal Cancer Diagnostic Testing—A New Paradigm Shift

ABSTRACT Colorectal cancer is the third leading cause of cancer related deaths and to date, the COVID-19 pandemic has led to major disruptions of the diagnosis and treatment pathways of this cancer, which may adversely affect survival outcomes for many years. Colorectal cancer pathways must be maintained at a near normal throughput with urgent attention to the backlog of patients to avoid a potential crisis of avoidable cancer deaths. A radical review and revamping of endoscopy services to improve efficiency during COVID-19 is urgently required. To date most endoscopy units have severely restricted their activity, except for time-critical diagnostic and therapeutic procedures. In the post- COVID-19 recovery phase, access to endoscopy services will increase but capacity will be reduced compared to before the pandemic, due to infection control measures. A pragmatic and safe strategy is urgently needed to clear the backlog of endoscopic procedures and for managing the new symptomatic referrals. We propose the use of non-invasive tests, such as FIT and mSEPT9 combined with “safety netting” to “rule out” colorectal cancer and to reduce the utilization of colonoscopy by up to 80% and limit the procedure to those patients at high risk of cancer.

Mo1676 COST EFFECTIVENESS OF MULTI-TARGET STOOL DNA TEST VERSUS COLONOSCOPY OR FECAL IMMUNOCHEMICAL TEST FOR COLORECTAL CANCER SCREENING AMONG ALASKA NATIVE PEOPLE

Alaska Native people have higher incidence and mortality from colorectal cancer (CRC) and lower CRC screening rates than U.S. whites. Alaska’s large and predominately roadless geography presents CRC screening challenges, particularly for endoscopy. The objective of this study was to estimate the cost-effectiveness of the multi-target stool DNA test (MT-sDNA) compared with colonoscopy and fecal immunochemical test (FIT) for Alaska Native people. A Markov model was used to evaluate effects of three CRC screening strategies for Alaska Native adults aged 40-75: colonoscopy every 10 years, annual FIT, or MT-sDNA testing every three years, over a 40-year period. An Alaska Native health-system perspective and Alaska Native-specific and national data were updated from previous models to incorporate new evidence on test performance; probabilistic sensitivity analyses explored perfect and imperfect screening adherence. The main outcome measures were CRC incidence and mortality; cost; quality-adjusted life years (QALYs); and incremental cost-effectiveness ratio (ICER). With perfect adherence, CRC incidence was reduced by 51.7% (95% CI: 46.3%-55.9%) using colonoscopy, 60.7% (95% CI: 56.5%-64.2%) using annual FIT, and 65.7% (95% CI: 62.9%-68.3%) using MT-sDNA. Compared with no screening, perfect adherence screening extends life by 0.15 QALYs per person with colonoscopy, 0.17 QALYs per person with FIT, and 0.19 QALYs per person with MT-sDNA. Screening by colonoscopy at ten-year intervals is the most expensive strategy, about $110M more than MT-sDNA and $127M more than FIT. With imperfect adherence (best case), MT-sDNA resulted in 0.12 QALYs/person vs. 0.05 QALYS/person by FIT and 0.06 QALYS/person by colonoscopy. Probabilistic sensitivity analyses supported the findings of the base-case analysis. Under perfect and imperfect adherence scenarios, MT-sDNA either dominates or is cost-effective (ICERs range from $1,740 to $75,868 per QALY saved) as compared with FIT and colonoscopy. Each strategy reduced costs and increased QALYs in comparison with no screening. Screening by MT-sDNA results in the largest savings of QALYs, in all adherence scenarios. In a Markov model analysis, we found that screening by MT-sDNA in the Alaska Native population is cost-effective as compared to screening by colonoscopy and FIT, for a wide range of adherence scenarios.

Multitarget stool DNA test compared with fecal occult blood test for colorectal cancer screening.

Patient screening is important for early diagnosis of colorectal cancer (CRC). The present study aimed to compare the multitarget stool DNA (mt-sDNA) test with the fecal occult blood test (FOBT) for CRC screening. A total of 151 individuals were screened using colonoscopy, mt-sDNA and FOBT for the detection of CRC and adenoma. The results of the mt-sDNA test and FOBT were compared with colonoscopy to examine their sensitivity and specificity. Subsequently, the sensitivity and specificity of the mt-sDNA test were compared with those of FOBT in CRC and large adenoma. Stool samples were collected from patients with CRC (n=50) or large adenoma (n=51), as well as from normal controls (n=50). The mt-sDNA test outperformed FOBT in detecting CRC with a sensitivity of 90.0% (45/50) vs. 42.0% (21/50), advanced adenoma with a sensitivity of 70.6% (36/51) vs. 19.6% (10/51), stage I–III CRC with a sensitivity of 91.9% (34/37) vs. 29.7% (11/37), and stage IV CRC with a sensitivity of 84.6% (11/13) vs. 76.9% (10/13). In addition, the mt-sDNA test exhibited a specificity of 94.0% (47/50) in detecting CRC, which was superior to FOBT with a specificity of 90.0% (45/50). Therefore, the mt-sDNA test may have higher sensitivity and specificity compared with FOBT in diagnosing both CRC and advanced adenoma.

PCN289 ESTIMATING THE IMPACT OF IMPERFECT ADHERENCE TO STOOL-BASED COLORECTAL CANCER SCREENING STRATEGIES ON COMPARATIVE EFFECTIVENESS USING THE CRC-AIM MICROSIMULATION MODEL

Adherence to colorectal cancer (CRC) screening strategies is imperfect and is ∼40% for annual fecal immunochemical tests (FIT) and ∼70% for triennial multi-target stool DNA (mt-sDNA) tests, based on cross-sectional data. Many microsimulation analyses have not considered differential adherence across screening modalities, which may lead to inaccurate conclusions regarding comparative effectiveness. We used the CRC-AIM microsimulation model to estimate the impact of varying adherence rates on the relative benefits of FIT and mt-sDNA screening.

Multitarget Stool DNA Screening: A Real-World Study

Multitarget stool DNA (mt-sDNA) testing has been available for colorectal cancer screening since 2014 (NEJM JW Gen Med May 1 2014 and N Engl J Med

Issue highlights

Issue highlights

Analysis of the effectiveness of two noninvasive fecal tests used to screen for colorectal cancer in average-risk adults

ObjectivesColorectal cancer (CRC) is the second leading cause of cancer-related death in the United States. Although a significant proportion of CRC cases and deaths are preventable by screening, the morbidity and mortality from CRC remains high and is attributed to suboptimal screening rates. Low levels of population CRC screening uptake may be due to reluctance toward invasiveness of some screening tests, embarrassment, exposure to anesthesia, and grueling preparation, especially for the invasive screening tests. Noninvasive tests overcome many of these barriers because they are more convenient and potentially more attractive to patients compared to invasive tests. This study uses Markov cohort simulation model developed with the help of TreeAge pro software to compare two noninvasive fecal CRC screens, fecal immunohistochemical test (FIT) and multitarget stool DNA test (Mt-sDNA) with no screening in order to identify the more effective noninvasive fecal test to screen for colorectal cancer in average-risk adults. Study designSimulation study developed with Markov model using TreeAge pro software, which included a hypothetical cohort at the average risk of developing colorectal cancer. MethodsMarkov model was used to compare population-level CRC-related cases and deaths averted, life-years gained (LYG), and colonoscopies required for two noninvasive CRC screening strategies compared with no screening: annual fecal immunohistochemical testing (FIT) and 3-yearly multitarget stool DNA testing (Mt-sDNA). The model simulated the natural history of the adenoma-carcinoma sequence in average-risk persons starting at age 50 years, and natural history parameters were estimated from the literature and via verification to data on precancerous lesions (i.e. adenomas) and CRC incidence. Screening strategies were then superimposed on the natural history component of the model, allowing for precancerous lesions to be detected and removed, or CRC to be detected and treated at a potentially earlier stage. The sensitivity and specificity for each screen for precancerous lesions and CRC were the performance parameters used to estimate the effectiveness. ResultsAnnual FIT was more effective than three yearly Mt-sDNA in reducing CRC cases, averting CRC-related deaths, and increasing the LYG compared to no screening. On average, annual FIT resulted in 3.5 fewer CRC cases, and 2.9 fewer CRC deaths per 1000 persons screened compared to 3-yearly Mt-sDNA. Annual FIT usage resulted in a 0.18 LYG compared to Mt-sDNA, which allowed 0.16 LYG, and an annual FIT screening led to a total of 203 more colonoscopies performed compared to Mt-sDNA. One-way sensitivity analysis conducted over the sensitivity rates of each screen by type of lesion showed that FIT remained the more effective strategy for all ranges of sensitivity. Threshold analysis results identified the lowest FIT sensitivity value at which Mt-sDNA performed better for conventional high-risk adenomas and CRC detection to be 0.16 and 0.052, respectively. ConclusionBoth the noninvasive screens were effective compared to no screening. Additionally, annual FIT as a first step noninvasive screening test for CRC appears to be more effective compared to three-yearly Mt-sDNA.

Multitarget Stool DNA Screening in Clinical Practice: High Positive Predictive Value for Colorectal Neoplasia Regardless of Exposure to Previous Colonoscopy.

OBJECTIVES:Multitarget stool DNA (MT-sDNA) testing has grown as a noninvasive screening modality for colorectal cancer (CRC), but real-world clinical data are limited in the post-FDA approval setting. The effect of previous colonoscopy on MT-sDNA performance is not known. We aimed to evaluate findings of colorectal neoplasia (CRN) at diagnostic colonoscopy in patients with positive MT-sDNA testing, stratified by patient exposure to previous colonoscopy.METHODS:We identified consecutive patients completing MT-sDNA testing over a 39-month period and reviewed the records of those with positive tests for neoplastic findings at diagnostic colonoscopy. MT-sDNA test positivity rate, adherence to diagnostic colonoscopy, and the positive predictive value (PPV) of MT-sDNA for any CRN and neoplastic subtypes were calculated.RESULTS:Of 16,469 MT-sDNA tests completed, testing returned positive in 2,326 (14.1%) patients. After exclusion of patients at increased risk for CRC, 1,801 patients remained, 1,558 (87%) of whom underwent diagnostic colonoscopy; 918 of 1,558 (59%) of these patients had undergone previous colonoscopy, whereas 640 (41%) had not. Any CRN was found in 1,046 of 1,558 patients (PPV = 67%). More neoplastic lesions were found in patients without previous colonoscopy (73%); however, the rates remained high among those who had undergone previous colonoscopy (63%, P < 0.0001). The large majority (79%) of patients had right-sided neoplasia.DISCUSSION:MT-sDNA has a high PPV for any CRN regardless of exposure to previous colonoscopy. Right-sided CRN was found at colonoscopy in most patients with positive MT-sDNA testing, representing a potential advantage over other currently available screening modalities for CRC.