Multitarget Stool DNA Test Research Articles

S337 Colonoscopy Quality Metrics After a Multi-Target Stool DNA or Fecal Immunochemical Test: A Systematic Review and Meta-Analysis

Introduction: Colorectal cancer (CRC) accounts for approximately 50,000 deaths or 14 deaths per 100,000 people yearly in the United States. Multi-target stool DNA (mt-sDNA) and fecal immunochemical test (FIT) are validated CRC screening strategies in average-risk asymptomatic individuals. This study aims to evaluate the colonoscopy quality metrics following a positive mt-sDNA test, FIT. Methods: We performed a comprehensive search in the databases of PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from inception through May 2022. Meta-analysis was performed by standard methodology using the random-effects model and heterogeneity was assessed using the I2% statistics. Outcomes of interest were adenoma detection rate (ADR), colorectal cancer detection rate (CRCDR), withdrawal time (WT), and cecal intubation rate (CIR). Results: 27 high-quality studies (97825 patients) were included in the analysis. 94161 had a positive FIT test in 23 studies and 3664 had positive mt-sDNA in 4 studies. The pooled WT after positive mt-sDNA was 16.1 minutes (95% CI 9.4-22.8, I2=99%), whereas after positive FIT was 11.6 minutes (10.9-12.3, 99%). The corresponding WT in the negative tests was 13.2 minutes (12.7-13.7) for mt-sDNA and 10.2 minutes (9.3-11.2) for FIT. The pooled ADR was 73% (69.9-75.8) and CRCDR was 1.9% (0.9-4.2) in mt-sDNA positive. The pooled ADR was 54.2% (49.8-58.4) and pooled CRCDR was 4% (3.2-4.9) in FIT positive. Pooled CIR were excellent: 99% (98.6-99.3) in mt-sDNA positive, and 96.8% (95.8-97.6) in FIT positive. Pooled rates are summarized in Table. Conclusion: Our meta-analysis demonstrated that positive mt-sDNA or FIT patients had a higher WT and CIR when compared to negative or unknown tests. ADR and CRCDR were high, however, it is not known if it is secondary to positive stool test or to longer WT. Future studies are needed to validate our findings and determine the cost-effectiveness of these screening tests. Table 1. - Colonoscopy quality metrics including withdrawal time, cecal intubation rate, adenoma detection rate and colorectal cancer detection rate after positive and negative multi-target stool DNA and fecal immunochemical test testing Outcomes Multi-target stool DNA (mt-sDNA) Fecal Immunochemical Test (FIT) Withdrawal time (WT), mean (95%CI) Positive: 16.1 (9.4-22.8) (SE: 3.4);4 studiesNegative: 13.2 (12.7-13.7) (SE: 0.2)1 study Positive: 11.6 (10.9-12.3) (SE: 0.3);22 studiesNegative: 10.2 (9.3-11.2) (SE: 0.5)6 studies Cecal intubation Rate (CIR), pooled rate (95%CI) Positive: 99% (98.6-99.3)2 studies Positive: 96.8% (95.8-97.6, 94%)12 studies Adenoma Detection Rate (ADR), pooled rate (95%CI) Positive: 73% (69.9-75.8)1 studyNegative: NR Positive: 54.2% (49.8-58.4, 97%)20 studiesNegative: 35.1% (30.5-39.9, 95%)6 studies Colorectal Cancer Detection Rate (CRCDR), pooled rate (95%CI) Positive: 1.9% (0.9-4.2, 81%)3 studiesNegative: 7.9% (2.6-21.8)1 study Positive: 4% (3.2-4.9, 88%)17 studiesNegative: 0.5% (0.2-1.6, 85%)5 studies Abbreviations: NR: not reported, SE: standard error, CI: confidence interval.

S252 Screening With FIT-DNA: Impact on Colonoscopy Withdrawal Time, Adenoma Detection and Endoscopist’s Recommendation for Follow-Up

Introduction: Limited data exist on colonoscopy after abnormal fecal immunochemical test (FIT)-DNA (a.k.a. multitarget stool DNA test). We hypothesized that endoscopists perform a more careful exam (e.g., longer withdrawal time (WT)) and recommend early re-screening after FIT-DNA+/negative colonoscopy due to expectations about test performance. We aimed to A) determine adenoma detection rate (ADR) and other lesion detection rates and B) assess endoscopist behavior regarding WT and recommendations after negative colonoscopy for 3 indications: 1) FIT-DNA+, 2) average-risk screening (SCR) and 3) abnormal fecal occult blood test (FOBT+, guaiac or FIT). Methods: Using GIQuIC data (2019-2022) from 727 endoscopy units, we identified patients aged 50-75 years undergoing colonoscopy for FIT-DNA+, SCR or FOBT+. We excluded colonoscopy with any other indications (e.g., family history), inadequate bowel preparation or incomplete exam. If pathology was obtained but results were not available, the record was excluded from pathology-related outcomes. Generalized estimating equations clustered by endoscopist were used to assess the association between indication and outcomes while adjusting for patient characteristics and endoscopist's screening ADR. Results: >1.8 million colonoscopies were included; demographics varied by indication (Table). FIT-DNA+ was associated with higher ADR (59.6%) than SCR (39.3%, p< 0.0001) and FOBT+ (53.8%, p< .0001) and greater detection of advanced neoplasia and sessile serrated lesions (Table). Among those with no pathology obtained on colonoscopy, WT was longer for FIT-DNA+ than for SCR and FOBT+. Among patients aged 50-65 years with no pathology and ASA < IV, a 10-year colonoscopy was recommended in only 80.1% of FIT-DNA+ patients vs. 87.2% of SCR and 86.5% of FOBT+. In multivariable models, compared to FIT-DNA+, SCR and FOBT+ are associated with shorter WT (p< 0.0001 for both), and lower odds of adenoma detection (OR 0.48 (95% CI 0.47-0.50) and 0.71 (0.68-0.74), respectively) and recommendations for re-screening in < 10 years (OR 0.64 (0.57-0.72) and 0.84 (0.74-0.96), respectively). Conclusion: FIT-DNA+ is associated with greater neoplasia detection than FOBT+ and SCR, but also with longer WT and more recommendations for early re-screening after a negative colonoscopy. Despite lower specificity of FIT-DNA vs. FOBT, endoscopists seem to have greater concern for missed pathology in FIT-DNA+/negative colonoscopies, leading to downstream impacts on healthcare utilization. Table 1. - Colonoscopy for Abnormal FIT-DNA vs. Average Risk Screening vs. Abnormal FOBT:Patient Characteristics, Findings and Follow-Up Recommendations After a Negative Exam FIT-DNA+(n=23,046) Average Risk Screening(n=1,760,840) FOBT+(n=26,455) Age, mean (sd) 64.2 (7.1) 58.7 (7.2) 63.8 (7.2) Male (%)Female (%) 9,939 (43.1)13,107 (56.9) 816,630 (46.4)944,210 (53.6) 12,698 (48.0)13,757 (52.0) White (%)Black of African American (%)Asian (%)Other (%)Unknown/Declined (%) 15,777 (68.5)1085 (4.7)211 (0.9)514 (2.2)5459 (23.7) 1,022,859 (58.1)171,348 (9.7)56,644 (3.2)68,966 (3.9)441,033 (25.1) 16,387 (61.9)2112 (8.0)959 (3.6)1224 (4.6)5773 (21.8) Non-Hispanic (%)Hispanic/Latino (%)Unknown/Decline 14,234 (61.8)560 (2.4)8252 (35.8) 1,018,724 (57.9)107,147 (6.1)634,969 (36.1) 16,691 (63.1)2407 (9.1)7357 (27.8) Total endoscopists contributing colonoscopies 2650 4845 3223 Endoscopist mean ADR‡(sd) with minimum 50 colonoscopies 39.1% (10.2)(Endoscopist n=2467) 39.2% (10.9)(Endoscopist n=3878) 39.5% (10.6)(Endoscopist n=3006) Colonoscopy Findings Adenoma Detection Rate (ADR) 59.6% *,§ 39.3% § 53.8% ADR for Males 67.6% *,§ 46.4% § 61.0% ADR for Females 53.6% *,§ 33.2% § 47.2% Advanced Neoplasia Detection± 22.2% *,§ 7.6% § 17.4% Sessile Serrated Lesion Detection 16.2% *,§ 8.2% † 8.8% Adenocarcinoma Detection 1.5% * 0.3% § 1.4% Analysis of Subgroup with No Polyps on Colonoscopy (i.e., No Pathology Obtained) Median Withdrawal Time, Minutes (interquartile range) (n=4211)8.5 (6.9-11.0) *,§ (n=673,519)7.8 (6.4-9.9) (n=7455)7.8 (6.3-10.1) Next Recommended Colonoscopy (limited to age 50-65, ASA< IV, exclude other or none)< 10 Years (%)10 Years (%) (n=2125)422 (19.9)1703 (80.1) (n=567,568)72,403 (12.8)495,165 (87.2) (n=4301)579 (13.5)3722 (86.5) Next Recommended Colonoscopy (limited to age 50-65, ASA< IV, exclude other or none)≤3 Years (%)4 or 5 Years (%)6-9 Years (%)10 Years (%)Excluded intervals n:OtherNone (n=2125)*,§ 76 (3.6)333 (15.7)13 (0.6)1703 (80.1) 1518 (n=567,568)§ 3840 (0.7)65,289 (11.5)3274 (0.6)495,165 (87.2) 2335974 (n=4301)65 (1.5)478 (11.1)36 (0.8)3722 (86.5) 2919 ‡ADR includes average risk screening only, ages 50-75, photodocumentation of the cecum, adequate bowel preparation.*p<0.0001 compared with average risk screening.§p<0.0001 compared with FOBT+.†p=0.0002 compared with FOBT+. ± Includes either 1) adenoma≥10 mm, with high grade dysplasia, or with villous component; OR 2) sessile serrated polyp (SSP)≥10 mm, SSP with dysplasia, or traditional serrated adenoma; OR 3) adenocarcinoma.

S273 Risk Factors Impacting Advanced Adenoma Detection Rate Following Negative Multitarget Stool DNA Testing

Introduction: Colonoscopy remains the gold standard for colorectal cancer (CRC) screening, but less invasive screening modalities have been employed more recently, including the multitarget Stool DNA (MT-sDNA or Cologuard) test, which combines detection of blood products with genetic markers in the stool. Data regarding the false-negative rate of the MT-sDNA test in real-world clinical practice is limited. Our primary aim was to determine the rate of false-negative MT-sDNA testing and evaluate for factors associated with higher false-negative rates within our health system. Methods: Adults (≥18 years old) with a negative MT-sDNA test between 2017 and 2022 and subsequent colonoscopy within three years of the MT-sDNA test, regardless of colonoscopy indication were included. Our primary outcome of interest was advanced adenoma (AA) detection rate, defined as adenoma with villous features, size ≥ 1.0 cm, high-grade dysplasia, or early invasive cancer. Demographic and procedural variables including age, sex, race, BMI, colonoscopy indication, polyp size, and polyp location were manually extracted from patient charts and compared between the two groups (AA vs. no AA) using chi-squared analysis. Results: A total of 370 patients met the inclusion criteria, of which 31 (8.4%) were found to have AA and 3 (0.81%) were found to have CRC on colonoscopy within 3 years of negative MT-sDNA test. There were no demographic differences between the two groups. AA detection rate was significantly higher in patients who underwent colonoscopy for GI bleeding (32.3% vs 14.2%, p=0.008) as opposed to other indications. Among patients who had polyps (N=148), AA detection was associated with more numerous polyps (2 [IQR 1-4] vs 1 [IQR 1-2], p < 0.001), and larger polyp size (14 [SD 5.1] vs 5.1 [SD 2.2], p < 0.001). AAs were also significantly more frequently found in the hepatic flexure (6.5% vs 0.3%, p=0.050) and transverse colon (41.9% vs 5.6%, p=0.002) compared to other locations (Table). Conclusion: The results of this study validate the 8% quoted false-negative rate for MT-sDNA testing shown in prior literature. Large polyps in the transverse colon and hepatic flexure are more likely to result in a false negative MT-sDNA test and therefore these locations should be examined in more detail during endoscope withdrawal. Finally, a negative MT-sDNA test result should be interpreted with caution and gastroenterologists should have a low threshold to perform a colonoscopy if otherwise clinically indicated. Table 1. - Baseline demographics and procedural variables in patients with negative MT-sDNA testing and advanced adenoma on colonoscopy (n=31) as compared to patients without advanced adenoma (n=339) Advanced Adenoma Non-Advanced Adenoma p value n=31 n=339 Male Sex, n(%) n(%) 16 51.6% 126 37.2% 0.114 Age – years Median (IQR) 67 59-74 66 59-71 0.157 Race n(%) 0.168 White 28 90.3% 272 80.2% Black 3 9.7% 59 17.4% Other 0 0.0% 8 2.4% BMI – kg/m2 Median (IQR) 30.7 25.6-35.2 30.1 26-34 0.807 Personal History of Colon Cancer n(%) 0 0.0% 3 0.9% 0.600 Family History of Colon Cancer n(%) 0 0.0% 32 9.4% 0.074 Personal History of IBD n(%) 0 0.0% 3 0.9% 0.600 Indication for Colonoscopy n(%) GI Bleeding 10 32.3% 48 14.2% 0.008 Iron deficiency anemia 4 12.9% 28 8.3% 0.380 Diarrhea 1 3.2% 34 10.0% 0.216 Constipation 0 0.0% 6 1.8% 0.457 Weight loss 0 0.0% 5 1.5% 0.497 Abnormal Imaging 2 6.5% 11 3.2% 0.355 IBD 0 0.0% 0 0.0% Screening 14 45.2% 193 56.9% 0.207 Other 0 0.0% 14 4.1% 0.250 Prep Quality n(%) Poor 2 6.5% 24 7.1% 0.896 Inadequate 0 0.0% 2 0.6% 0.669 Fair 10 32.3% 79 23.3% 0.265 Adequate 2 6.5% 35 10.3% 0.493 Good 17 54.8% 187 55.2% 0.972 Excellent 0 0.0% 12 3.5% 0.288

S248 Disparities in Rates of Multitarget Stool DNA Test Completion for Colorectal Cancer Screening

S248 Disparities in Rates of Multitarget Stool DNA Test Completion for Colorectal Cancer Screening

S296 Appropriateness and Completion of Multitarget Stool DNA Testing in Primary and Subspecialty Care

S296 Appropriateness and Completion of Multitarget Stool DNA Testing in Primary and Subspecialty Care

Cost-Effectiveness of Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors Treated with Procarbazine and/or Infradiaphragmatic Radiotherapy.

Hodgkin lymphoma survivors treated with infradiaphragmatic radiotherapy (IRT) and/or procarbazine have an increased risk of developing colorectal cancer. We investigated the cost-effectiveness of colorectal cancer surveillance in Dutch Hodgkin lymphoma survivors to determine the optimal surveillance strategy for different Hodgkin lymphoma subgroups. The Microsimulation Screening Analysis-Colon model was adjusted to reflect colorectal cancer and other-cause mortality risk in Hodgkin lymphoma survivors. Ninety colorectal cancer surveillance strategies were evaluated varying in starting and stopping age, interval, and modality [colonoscopy, fecal immunochemical test (FIT, OC-Sensor; cutoffs: 10/20/47 μg Hb/g feces), and multi-target stool DNA test (Cologuard)]. Analyses were also stratified per primary treatment (IRT and procarbazine or procarbazine without IRT). Colorectal cancer deaths averted (compared with no surveillance) and incremental cost-effectiveness ratios (ICER) were primary outcomes. The optimal surveillance strategy was identified assuming a willingness-to-pay threshold of €20,000 per life-years gained (LYG). Overall, the optimal surveillance strategy was annual FIT (47 μg) from age 45 to 70 years, which might avert 70% of colorectal cancer deaths in Hodgkin lymphoma survivors (compared with no surveillance; ICER:€18,000/LYG). The optimal surveillance strategy in Hodgkin lymphoma survivors treated with procarbazine without IRT was biennial FIT (47 μg) from age 45 to 70 years (colorectal cancer mortality averted 56%; ICER:€15,000/LYG), and when treated with IRT and procarbazine, annual FIT (47 μg) surveillance from age 40 to 70 was most cost-effective (colorectal cancer mortality averted 75%; ICER:€13,000/LYG). Colorectal cancer surveillance in Hodgkin lymphoma survivors is cost-effective and should commence earlier than screening occurs in population screening programs. For all subgroups, FIT surveillance was the most cost-effective strategy. Colorectal cancer surveillance should be implemented in Hodgkin lymphoma survivors.

Patterns of initial colorectal cancer screenings after turning 50 years old and follow-up rates of colonoscopy after positive stool-based testing among the average-risk population

Objectives Effective colorectal cancer (CRC) screening requires proper adherence beginning at the recommended screening age. For those with positive results on stool-based tests (SBTs), a follow-up colonoscopy is warranted. The objectives of this study were to 1) examine initial screening rates after turning 50 years old; and 2) assess rates of follow-up colonoscopy after a positive SBT. Methods This retrospective study used de-identified administrative claims data from 01/01/2006 to 06/30/2020 for commercially insured and Medicare Advantage enrollees. For objective 1, the index year was the year enrollees turned 50. Rates of CRC screening during and after the index year were captured. For objective 2, the index date was the claim date of a fecal immunochemical test (FIT) or multitarget stool DNA test (mt-sDNA) where linked lab data indicated a positive test result. Rates and time to follow-up colonoscopy after a positive SBT were assessed. Results Approximately 53% of enrollees initiated CRC screening within five years after turning 50 (50+ cohort N = 718,562). Among enrollees with an available lab result indicating a positive SBT (N = 7329; 2110 FIT and 5219 mt-sDNA), overall follow-up colonoscopy within 6 months of the positive result was less than optimal (65%) and varied by modality; 72% vs 46% (p < .001) among enrollees with a positive mt-sDNA test compared to FIT test, respectively. Conclusion There is potential for improving CRC screening among the eligible average-risk population, both to start screening once they reach the screening-eligible age, and to complete the CRC screening paradigm after a positive stool-based screen.

PCR94 Evaluation of a Multimedia Outreach Campaign for Multi-Target Stool DNA Test for Colorectal Cancer Screening Among Non-Medicare Employer Population

Survival rates are higher among colorectal cancer (CRC) patients if the cancer is detected earlier. Despite compelling evidence, screening rates are lower than the recommended thresholds. Increasing public awareness through interventions may improve screening completions. The current prospective study examined the effectiveness of a a multi-media intervention campaign on multi-target stool DNA (mt-sDNA) completion rates and follow-up colonoscopy rates.

Evaluation of a multimedia outreach campaign for a multi-target stool DNA test for colorectal cancer screening among non-medicare employer population in the United States

Regular and timely screenings for colorectal cancer (CRC) can improve survival through early cancer detection. The current prospective intervention study assessed the effectiveness of a CRC screening outreach campaign via a multi-media campaign featuring articles in a multi-topic benefits newsletter that was both printed/mailed to homes and emailed to Metro Nashville Public Schools (MNPS) employees and their dependents in the United States. Individuals were included if they were between 45 and 64 years old. The mailed newsletter was sent to 5631 active employees, 868 under 65 retirees, and 4046 retirees with Medicare. The open rate was the highest for the third email (n = 3018; 53.3%). The click-through rate was also the highest for the third email (n = 203;6.7%). Among those who opened at least one of the emails or received a mailed newsletter, 119 members completed the assessment (conversion rate = 3.9%). Among this population, the mt-sDNA completion rate was 64.5% (69 orders completed out of 107 ordered mt-sDNA kits). All 6 patients with a positive mt-sDNA result underwent a follow-up colonoscopy (FU-CY) with the mean (±SD) days to FU-CY among those with positive mt-sDNA test results was 49 (±27) days (median = 42 days). Using emails in conjunction with other targeted interventions to outreach and educate members regarding CRC screening may be an effective strategy to enhance mt-sDNA completion rates.

Implementing a mHealth intervention to increase colorectal cancer screening among high-risk cancer survivors treated with radiotherapy in the Childhood Cancer Survivor Study (CCSS)

BackgroundCancer survivors treated with any dose of radiation to the abdomen, pelvis, spine, or total body irradiation (TBI) are at increased risk for developing colorectal cancer (CRC) compared to the general population. Since earlier detection of CRC is strongly associated with improved survival, the Children’s Oncology Group (COG) Long-Term Follow-Up Guidelines recommend that these high-risk cancer survivors begin CRC screening via a colonoscopy or a multitarget stool DNA test at the age of 30 years or 5 years following the radiation treatment (whichever occurs last). However, only 37% (95% CI 34.1–39.9%) of high-risk survivors adhere to CRC surveillance. The Activating cancer Survivors and their Primary care providers (PCP) to Increase colorectal cancer Screening (ASPIRES) study is designed to assess the efficacy of an intervention to increase the rate of CRC screening among high-risk cancer survivors through interactive, educational text-messages and resources provided to participants, and CRC screening resources provided to their PCPs.MethodsASPIRES is a three-arm, hybrid type II effectiveness and implementation study designed to simultaneously evaluate the efficacy of an intervention and assess the implementation process among participants in the Childhood Cancer Survivor Study (CCSS), a North American longitudinal cohort of childhood cancer survivors. The Control (C) arm participants receive electronic resources, participants in Treatment arm 1 receive electronic resources as well as interactive text messages, and participants in Treatment arm 2 receive electronic educational resources, interactive text messages, and their PCP’s receive faxed materials. We describe our plan to collect quantitative (questionnaires, medical records, study logs, CCSS data) and qualitative (semi-structured interviews) intervention outcome data as well as quantitative (questionnaires) and qualitative (interviews) data on the implementation process.DiscussionThere is a critical need to increase the rate of CRC screening among high-risk cancer survivors. This hybrid effectiveness-implementation study will evaluate the effectiveness and implementation of an mHealth intervention consisting of interactive text-messages, electronic tools, and primary care provider resources. Findings from this research will advance CRC prevention efforts by enhancing understanding of the effectiveness of an mHealth intervention and highlighting factors that determine the successful implementation of this intervention within the high-risk cancer survivor population.Trial registrationThis protocol was registered at clinicaltrials.gov (identifier NCT05084833) on October 20, 2021.

Colonoscopy Findings in FIT+ and mt-sDNA+ Patients versus in Colonoscopy-only Patients: New Hampshire Colonoscopy Registry Data.

Few studies compare fecal immunochemical test (FIT) and multi-target stool DNA (mt-sDNA) outcomes in practice. We compared colonoscopy yield following FIT+ or mt-sDNA+ tests to colonoscopies without preceding stool tests in the comprehensive population-based New Hampshire Colonoscopy Registry (NHCR). Outcomes were any neoplasia and an ordered outcome: adenocarcinoma, advanced neoplasia (adenoma/serrated polyp ≥ 1 cm/villous/high-grade dysplasia), nonadvanced neoplasia, or normal. Our total sample included 306 mt-sDNA+ (average age ± SD 67.0 ± 7.9), 276 FIT+ (66.6 ± 8.7), and 50,990 colonoscopy-only patients (61.8 ± 8.1). Among average-risk patients (N = 240 mt-sDNA+, N = 194 FIT+, N = 26,221 colonoscopy only), mt-sDNA+ patients had a higher risk for any neoplasia (67.1%) compared with FIT+ (54.6%, P = 0.00098) or colonoscopy (40.8%, P < 0.0001). Severity of findings and histology subtypes differed across the three groups (P < 0.0001 for both), with a higher yield of advanced findings in mt-sDNA+ patients. In particular, clinically relevant serrated polyps (hyperplastic polyps ≥10 mm/traditional serrated adenomas/sessile serrated polyps) were detected at a higher frequency in mt-sDNA+ patients as compared with FIT+ or colonoscopy-only patients. Even after adjustment, patients with positive mt-sDNA [OR = 2.82; 95% confidence interval (CI), 2.00-4.02] or FIT+ tests (OR = 1.67; 95% CI, 1.19-2.36) were more likely to have histologically more advanced findings than colonoscopy alone. At follow-up colonoscopy, mt-sDNA+ tests were more likely to predict neoplasia than FIT+, largely due to increased detection of serrated polyps. Prevention Relevance: Colorectal cancer screening options include colonoscopy and stool-based tests, including the fecal immunochemical test (FIT) and the multi-target stool DNA (mt-sDNA) test which, if positive, must be followed by a colonoscopy. Assessing "real-world" outcomes of colonoscopies following positive stool tests can inform their clinical use. See related Spotlight, p. 417.

A Practical Overview of the Stool DNA Test for Colorectal Cancer Screening.

The multitarget stool DNA test with fecal immunochemical test (sDNA-FIT) is recommended by all major US guidelines as an option for colorectal cancer screening. It is approved by the Food and Drug Administration for use in average-risk individuals aged 45 years and older. The sDNA-FIT tests for 11 biomarkers, including point mutations in KRAS, aberrant methylation in NDRG4 and BMP3, and human hemoglobin. Patients collect a stool sample at home, send it to the manufacturer's laboratory within 1 day, and the result is reported in approximately 2 weeks. Compared with FIT, sDNA-FIT has higher sensitivity but lower specificity for colorectal cancer, which translates to a higher false-positive rate. A unique feature of sDNA-FIT is the manufacturer's comprehensive patient navigation system, which operates 24 hours a day and provides active outreach for patient education and reminders in the first month after a test is ordered. Retesting is recommended every 1–3 years, although the optimal testing interval has not yet been determined empirically. The cost of sDNA-FIT is $681 without insurance, but Medicare and most private insurers cover it with no copay or deductible.

Cross-cultural validation of stool Based Colorectal cancer screening methods in the North West of Iran

BackgroundGlobally, colorectal cancer (CRC) is the third most common cancer and the second leading cause of death from cancer. Incidence and mortality from CRCboth can be reduced and prevented using screening and early detection programs. The current study aimed to assess the feasibility of the colorectal cancer screening program in Northwest of Iran. MethodsThe study designed as a cross-cultural analytic study, to evaluate the diagnostic accuracy of stool-based tests compared with colonoscopy, during 2016–2020. All individuals first were assessed with our CRC risk assessment tool, then eligible volunteers entered the study. Colonoscopy was performed on all participants, also stool-based tests including traditional guaiac, high-sensitivity guaiac-based, fecal immunochemical test (FIT), and multitarget stool DNA (Mt-sDNA) panel tests were performed. ResultsMt-sDNA test panel had a sensitivity of 77.8% (95% CI: 40–97.2)for detecting colorectal cancer with a specificity of 91.2% (95% CI:85.4–95.2). The FIT test alone had a lower sensitivity (66.7%; 95% CI:29.9–92.5) and almost the same specificity of 93.9% (95% CI: 88.7–97.2) for cancer detection. Mt-sDNA test had better diagnostic accuracy than the FIT (AUC = 0.85 vs 0.80), and is a more useful screening test. Positive and negative predictive values for cancer detection for both Mt-sDNA and FIT tests were almost the same results, however Mt-sDNA test had better NPV results than the FIT test alone. ConclusionOur results showed that both Mt-sDNA panel and the FIT test had acceptable cut-off points for cancer detection, however, Mt-sDNA test had better diagnostic accuracy.

Detection of High-Risk Sessile Serrated Lesions: Multitarget Stool DNA Versus CT Colonography.

BACKGROUND. The serrated pathway for colorectal cancer (CRC) development is increasingly recognized. Sessile serrated lesions (SSLs) that are large (≥ 10 mm) and/or have dysplasia (i.e., high-risk SSLs) are at higher risk of progression to CRC. Detection of SSLs is challenging given their predominantly flat and right-sided location. The yield of noninvasive screening tests for detection of high-risk SSLs is unclear. OBJECTIVE. The aim of this study was to compare noninvasive screening detection of high-risk SSLs between the multitarget stool DNA (mt-sDNA) test and CT colonography (CTC). METHODS. This retrospective study included 7974 asymptomatic adults (4705 women, 3269 men; mean age, 60.0 years) who underwent CRC screening at a single center by mt-sDNA from 2014 to 2019 (n = 3987) or by CTC from 2009 to 2019 (n = 3987). Clinical interpretations of CTC examinations were recorded. Subsequent colonoscopy findings and histology of resected polyps were also recorded. Chi-square or two-sample t tests were used to compare results between mt-sDNA and CTC using 6-mm and 10-mm thresholds for test positivity. RESULTS. The overall colonoscopy referral rate for a positive screening test was 13.1% (522/3987) for mt-sDNA versus 12.2% (487/3987; p = .23) and 6.5% (260/3987; p < .001) for CTC at 6-mm and 10-mm thresholds, respectively. The PPV for high-risk SSLs was 5.5% (26/476) for mt-sDNA versus 14.4% (66/457; p < .001) and 25.9% (63/243; p < .001) for CTC at the 6-mm and 10-mm thresholds, respectively. The overall screening yield of high-risk SSLs was 0.7% (26/3987) for mt-sDNA versus 1.7% (66/3987; p < .001) and 1.6% (63/3987; p < .001) for CTC at 6-mm and 10-mm thresholds, respectively. CONCLUSION. CTC at 6-mm and 10-mm thresholds had significantly higher yield and PPV for high-risk SSLs compared with mt-sDNA. CLINICAL IMPACT. The significantly higher detection of high-risk SSLs by CTC than by mt-sDNA should be included in discussions with patients who decline colonoscopy and opt for noninvasive screening.

Adherence with the multitarget stool DNA test for colorectal cancer screening in rural southeastern Kentucky.

64 Background: Colorectal cancer (CRC) screening has shown to improve early detection and reduce mortality. Despite, the availability of multiple screening tests for CRC, the current screening rates remains below the national goal. The multi-target stool (MTS) DNA test (commercially known as Cologuard) has contributed to an increase in population adherence to CRC screening and is currently recommended by multiple guidelines. Southeastern Kentucky (SE KY) has a high incidence of colorectal cancer and a low rate of CRC screening. The aim of this study is to assess the adherence to the MTSDNA test in rural SE KY. Methods: A retrospective review of all patients 45 and older with a MTSDNA test ordered between August 2020 and February 2021 at a large primary care group in SE KY. All patients had Tests ordered and kits delivered. Cross-sectional adherence was defined as completion and return of the kit within 180 days from test order and was assessed as overall adherence and by patient characteristics including age, sex and healthcare coverage. Results: 450 tests were ordered. 160 (35%) were male and 290 (65%) females. Mean age was 62 with age range (46-87). 207 tests were returned with a cross-sectional adherence of 46%. Adherence was significantly lower for age 45 - 55 at 35.2% (26.2-45.2) compared to age 55 - 65 at 48.9% (40.9-56.3), 65 and older at 50.0% (42.3-57.7) (P = 0.04). Highest adherence with Medicaid coverage 65.4% [44.3-82.8] and lowest in Managed Care Organization (MCO) coverage 34.0% [4.7-44.2] (P &lt; 0.01). Gender was not associated with adherence (P = 0.75). Conclusions: This retrospective study showed that only 46% of patients were adherent to the MTS DNA test for colorectal screening which is significantly lower than previously reported in larger studies and further studies are needed to identify the barriers to non-adherence to this test, especially in the younger population with alarming increase in incidence of CRC. There is impending need to implement different strategies to improve screening adherence.

Can second-generation multitarget stool DNA panels reliably detect colorectal cancer and advanced precancerous lesions?

63 Background: Population-based colorectal cancer (CRC) screening can reduce mortality by detecting and removing advanced precancerous lesions (APL) and early-stage invasive disease. One guideline-included strategy is the multi-target stool DNA test (mt-sDNA), which combines detection of methylation DNA markers (MDMs), KRAS mutations, and fecal hemoglobin. Since the mt-sDNA pivotal study was conducted, novel biomarkers have been discovered. A panel of highly discriminant MDMs ( LASS4, LRRC4, PPP2R5C, and reference marker ZDHHC1) was identified through a blinded, case-control study of archival specimens. Here, we evaluated the performance of this novel mt-sDNA panel, combined with fecal hemoglobin, in archival stool samples weighted to early-stage CRC and prospectively collected APL, simulating a screening population. Methods: The verification study featured 777 samples—210 cases (112 CRC [49 stage I, 38 stage II, 17 stage III, and 8 stage IV] and 98 APL) and 567 controls (176 non-APL and 391 colonoscopy-negative)—from three trials (NCT01397747, NCT01260168, and NCT02503631). Median APL size was 12 mm (interquartile range: 10 mm to 15 mm), with 86.7% adenomas (n = 85) and 13.3% sessile serrated polyps (SSPs; n = 13). The average age was 65.5 years for cases (57% men) and 63.2 for controls (47% men). Samples were processed through homogenization, targeted MDM capture, bisulfite conversion, and MDM quantitation using Long‐probe Quantitative Amplified Signal (LQAS). Fecal hemoglobin was quantified using enzyme-linked immunosorbent assay (ELISA). Samples were split into stratified 75%/25% training-testing sets and model outcomes were cross-validated 1,000 times. Results: Mean performance from the cross-validation analysis is summarized in the table below. Overall sensitivity was 95.2% for CRC and 57.2% for APL, with specificities of 89.8% (no CRC/APL) and 92.4% (no neoplasia). Subgroup analyses showed high sensitivity for early-stage CRC, with 93.4% at stage I and 94.2% at stage II. By APL subtype, sensitivity was 82.9% for high-grade dysplasia, 73.4% for villous lesions, 49.8% for tubular lesions, and 30.2% for SSPs. Conclusions: These data support high sensitivity and specificity for a second-generation mt-sDNA panel. A multicenter pivotal trial evaluating the panel is underway (NCT04144738). [Table: see text]

Diagnostic accuracy of multitarget stool DNA testing for colorectal cancer screening: A systematic review and meta-analysis

IntroductionThis study aimed to collect and summarize test data and conduct a meta-analysis, with respect to the Multitarget Stool DNA test sensitivity and specificity, compared to colonoscopy. Material and methodsAll manuscripts were screened for eligibility according to inclusion criteria. Participants were a normal population at an average risk of developing CRC. Intervention was Stool based and DNA panel tests compared with colonoscopy, and outcome was detection of CRC and any pre-cancerous lesions. Inter-study and inconsistency (using the I-squared test) were assessed. ResultsMeta-analyses of the Mt-sDNA test showed a combined sensitivity of 89%, 51%, and 76% for the detection of CRC, advanced adenoma (AA), and combined CRC and AA, respectively. The overall specificity was 91%, 89%, and 90% for the detection of CRC, AA, and combined CRC and AA, respectively. ConclusionMt-sDNA had significantly acceptable diagnostic accuracy for CRC and AA diagnosis, but still has lower sensitivity and specificity than colonoscopy.

Optimal Noninvasive Colon Cancer Screening Modality in Patients Not Receiving Colonoscopy

Colon cancer is the third most common among cancer deaths in the US for both men and women. The incidence of colonoscopy has been soaring in younger patients, which led to changes in recent United States Preventive Services Task Force (USPSTF) guidelines to reduce the age for screening from 50 years to 45 years. Demand for colonoscopy services is surging due to increased incidences of colorectal cancer (CRC) in the both aging and younger population. Increased referrals have led to an insufficient workforce in hospitals and long waiting lists. Further, results from colonoscopy reveal a low percentage of CRC or another severe bowel disease (SBD). Therefore, colon cancer screening is a growing concern, particularly in patients who otherwise have a very long-life expectancy, and who are most likely to benefit from screening. Another reason to boost CRC screening is to minimize the load on hospitals by reducing the patients that undergo colonoscopy unnecessarily because only a low percentage of CRC occurrence is observed in individuals undergoing colonoscopy. In recent years, there are a variety of screening options available for CRC. Noninvasive alternatives include fecal immunochemical test (FIT), multitarget stool DNA testing (MT-sDNA, available under the brand name Cologuard), computed tomography (CT) colonography (previously called virtual colonoscopy), guaiac-based fecal occult blood testing (gFOBT), and capsule colonoscopy (CC). These tests have varied the degree of evidence supporting their use. This study focuses on the most recent survey and efficacy of noninvasive methods to prevent and detect colorectal cancer (CRC).

Impact of the Sessile Serrated Polyp Pathway on Predicted Colorectal Cancer Outcomes.

Approximately 20%-30% of colorectal cancers (CRCs) arise from the serrated polyp pathway. CRC screening options have differential sensitivity to detect sessile serrated polyps (SSPs). We used the Colorectal Cancer and Adenoma Incidence and Mortality Microsimulation Model (CRC-AIM) to assess how the detection of SSPs impacts predicted life years gained (LYG), CRC incidence, and CRC mortality with multitarget stool DNA (mt-sDNA) or fecal immunochemical test (FIT) screening. A simulated cohort of average-risk US individuals underwent triennial mt-sDNA or annual FIT screening between ages 45-75 years. SSP-attributed CRCs were modeled at 0% (base case), 14.3%, 20%, and 30%, in combination with 4 adherence & attendance scenarios: S1: 100% stool-screening adherence/100% follow-up colonoscopy attendance after a positive stool test; S2: reported stool-screening adherence (mt-sDNA= 71%; FIT= 43%)/100% follow-up colonoscopy attendance; S3: reported stool-screening adherence/reported follow-up colonoscopy attendance (mt-sDNA= 72%; FIT= 47%); and S4: reported stool-screening adherence/72% follow-up colonoscopy attendance. Outcomes were per 1000 individuals. Sensitivity analyses used ranges of stool-screening adherence or follow-up attendance. At S1, S2, S3, and S4, LYG with FIT at the base case (0% SSP-attributed CRC) was 346.7, 279.3, 126.6, and 196.1, respectively, and with mt-sDNA was 324.6, 311.8, 215.8, and 215.8, respectively. Among the 4 adherence/attendance scenarios, modeling SSP-attributed CRCs decreased LYG by 4.9-20.9 with FIT and 2.0-5.1 with mt-sDNA. At S3 and 30% SSP-attributable CRCs, mt-sDNA had 95.1 more LYG, 21.5% greater CRC incidence reduction, and 22.2% greater CRC mortality reduction than FIT. Incorporating SSPs and real-world adherence into the CRC-AIM modeling analyses yielded more practice-relevant estimates of CRC screening outcomes and should be applied in future studies to afford more appropriate assessment of comparative effectiveness estimates between guideline-endorsed screening options.

Initial validation of a self-report questionnaire based on the Theoretical Domains Framework: determinants of clinician adoption of a novel colorectal cancer screening strategy

BackgroundColorectal cancer (CRC) screening for average risk adults age 45 and older continues to be underutilized in the USA. One factor consistently associated with CRC screening completion is clinician recommendation. Understanding the barriers and facilitators of clinical adoption of emerging CRC screening strategies is important in developing effective intervention strategies to improve CRC screening rates. We aimed to develop a questionnaire based on the Theoretical Domains Framework (TDF) to assess determinants of clinical adoption of novel CRC screening strategies, using the multi-target stool DNA test (mt-sDNA; Cologuard®) as an example, and test the psychometric properties of this questionnaire on a sample of US clinicians.MethodsA web survey was administered between November and December 2019 to a national panel of clinicians including primary care clinicians (PCCs) and gastroenterologists (GIs) to assess 10 TDF constructs with 55 items. Confirmatory factor analysis (CFA) was used to examine whether the a priori domain structure was supported by the data. Discriminant validity of domains was tested with Heterotrait-Monotrait ratio (HTMT). Internal consistency for each scale was assessed using Cronbach’s alpha. Criterion validity was assessed with self-reported mt-sDNA use and mt-sDNA recommendation as the outcomes.ResultsComplete surveys were received from 814 PCCs and 159 GIs (completion rate, 24.7% of 3299 PCCs and 29.6% of 538 GIs). Providers were excluded from analysis if they indicated not recommending CRC screening to average-risk patients (final N = 973). The final questionnaire consisted of 38 items covering 5 domains: (1) knowledge; (2) skills; (3) identity and social influence; (4) optimism, beliefs about consequences, and intentions; and (5) environmental context and resources. CFA results confirmed a reasonable fit (CFI = 0.948, SRMR = 0.057, RMSEA = 0.080). The domains showed sufficient discriminant validity (HTMT < 0.85), good internal consistency (McDonald’s omega > 0.76), and successfully differentiated providers who reported they had ordered mt-sDNA from those who never ordered mt-sDNA and differentiated providers who reported routinely recommending mt-sDNA from those who reported not recommending mt-sDNA.ConclusionsFindings provide initial evidence for the validity and internal consistency of this TDF-based questionnaire in measuring potential determinants of mt-sDNA adoption for average-risk CRC screening. Further investigation of validity and reliability is needed when adapting this questionnaire to other novel CRC screening strategy contexts.