Association of Endoscopist Colonoscopy Quality Measures With Follow-Up Colonoscopy Outcomes After Positive Stool Tests (Multitarget Stool DNA or Fecal Immunochemical Test): Retrospective Cross-Sectional Analysis of Data From the New Hampshire Colonoscopy Registry.

INTRODUCTION: Negative colonoscopies following positive stool tests could result from stool test characteristics or from the quality of endoscopist performance. We used New Hampshire Colonoscopy Registry data to examine the association between endoscopist detection rates and polyp yield in colonoscopies performed for positive fecal immunochemical test (FIT) or multitarget stool DNA (mt-sDNA) test to evaluate the degree to which positive stool tests followed by negative colonoscopy ("false positives") vary with endoscopist quality. In addition, we investigated the frequency of significant polyps in the subgroup of highest quality colonoscopies following positive stool tests. METHODS: We compared the frequencies of negative colonoscopies and of specific polyps following positive stool tests across quartiles of endoscopist adenoma detection rate (ADR) and clinically significant serrated polyp detection rate (CSSDR). RESULTS: Our sample included 864 mt-sDNA+ and 497 FIT+ patients. We found a significantly lower frequency of negative colonoscopies following positive stool tests among endoscopists with higher ADR and CSSDR, particularly in the 2 highest quartiles. In addition, detection of any adenoma after a positive stool test for endoscopists in the fourth ADR quartile was 63.3% (FIT+) and 62.8% (mt-sDNA+). Among endoscopists in the fourth CSSDR quartile, sessile serrated lesions were found in 29.2% of examinations following a positive mt-sDNA and in 13.5% following FIT+ examinations. DISCUSSION: The frequency of negative colonoscopies after positive stool tests was significantly higher in examinations performed by endoscopists with low ADR and CSSDR. Our results also suggest a benchmark target of at least 40% for ADR in patients with mt-sDNA+ or FIT+ tests and 20% for sessile serrated lesions in mt-sDNA+ patients.

Colorectal Neoplasia Detection in Individuals With Positive Multitarget Stool DNA Tests: Data From the New Hampshire Colonoscopy Registry.

BACKGROUND: The US Preventive Services Task Force (USPSTF) includes multitarget stool DNA (mt-sDNA) testing as a colorectal cancer (CRC) screening option in average-risk individuals, but data on colonoscopy outcomes after positive mt-sDNA tests in community settings are needed. AIM: The aim of this study was to investigate colonoscopy outcomes and quality following positive mt-sDNA in the population-based New Hampshire Colonoscopy Registry. METHODS: We compared colonoscopy outcomes and quality between age-matched, sex-matched, and risk-matched patients from 30 endoscopy practices with and without a preceding positive mt-sDNA test. Main outcomes were colonoscopy findings of CRC, advanced noncancerous neoplasia, nonadvanced neoplasia, or normal examination. Quality measures included withdrawal time, bowel preparation quality, examination completion, and percentage of average-risk individuals with normal colonoscopies receiving a USPSTF-recommended 10 year rescreening interval. RESULTS: Individuals with positive mt-sDNA tests (N=306, average age 67.0 y; 61.8% female) were significantly more likely than colonoscopy-only patients (N=918, 66.2 y; 61.8% female) to have CRC (1.3% vs. 0.4%) or advanced noncancerous neoplasia (27.1% vs. 8.2%) (P<0.0001). Neoplasia was found in 68.0% of patients having colonoscopy after a positive mt-sDNA test, (positive predictive value, was 68.0%), versus 42.3% of patients with colonoscopy only (P<0.0001). No significant differences in colonoscopy quality measures were observed between cohorts. CONCLUSIONS: Colonoscopy after a positive mt-sDNA test was more frequently associated with CRC and colorectal neoplasia than colonoscopy alone. Positive mt-sDNA tests can enrich the proportion of colonoscopies with clinically relevant findings. Follow-up recommendations suggest that endoscopists do not inappropriately shorten rescreening intervals in mt-sDNA-positive patients with normal colonoscopy. These findings support the clinical utility of mt-sDNA for CRC screening in community practice.

Recruitment strategies and consent rates in a national prospective colorectal cancer screening cohort: results from year 1 of the Voyage Study.

OBJECTIVE: To identify the optimal incentive protocol for maximising participation while managing study costs during the Voyage trial. DESIGN: Prospective cohort (Voyage trial) of colorectal cancer (CRC) incidence and mortality outcomes in individuals screened with multitarget stool DNA (mt-sDNA) served as the population. A subset was randomised to receive postage stamps as a pre-consent incentive, or as a post-consent incentive after completion of the consent and questionnaire. Descriptive statistics from year 1 are reported. RESULTS: During year 1 of the Voyage trial, a total of 600 258 individuals with mt-sDNA orders received at Exact Sciences Laboratories were randomly selected and invited to participate. Of those, 26 429 (4.4%) opted in, 14 365 of whom (54.3%) consented. The opt-in and consent samples were similar to the target population with respect to sex but differed by geographic residence and age (p<0.001). For the embedded incentive experiment, 2333 were randomised to the pre-incentive arm, while 2342 were randomised to the post-incentive arm. Overall consent rate in the incentive trial was 56.4% (60.9% for the pre-consent incentive arm (1421/2333) vs 52.0% for the post-consent incentive arm (1217/2342), p<0.001). Cost reduction was observed for the pre-consent incentive group, and higher response rates were seen among older versus younger individuals. CONCLUSIONS: Pre-consent incentive option was associated with a higher participation rate and lower costs and was used for the remainder of study recruitment. CRC incidence and mortality vary with age; thus, adjusting for differential participation by age and region will be important in analyses of Voyage data. TRIAL REGISTRATION NUMBER: NCT04124406.

What do 'false-positive' stool tests really mean? Data from the New Hampshire colonoscopy registry.

We utilized the population-based New Hampshire Colonoscopy Registry to calculate false discovery rates (FDR) and positive predictive values (PPVs) using three 'positive' colonoscopy definitions. Understanding the frequency of meaningful 'true positive' mt-sDNA and Fecal Immunochemical Test (FIT) results can optimize the use of these colorectal cancer (CRC) screening tests. We calculated FDR (positive stool test followed by negative colonoscopy divided by all positive stool tests) and PPV for mt-sDNA and FIT cohorts using the following definitions: 1) DeeP-C Study (CRC, adenomas/serrated polyps ≥ 1 cm, villous/High Grade Dysplasia); 2) < 10 year US Multi-Society Task Force (USMSTF) follow-up: DeeP-C findings & ≥1 sessile serrated polyps (SSPs) < 1 cm (with/without dysplasia) or ≥ 1 tubular adenomas < 1 cm. 3) Clinically Significant: DeeP-C + USMSTF + clinically significant serrated polyps: traditional serrated adenomas, SSPs, hyperplastic polyps (HPs) > 1 cm, and 5-9 mm proximal HPs. The sample included 549 mt-sDNA + and 410 FIT + and patients (mean age 66.4, 43.0% male). Using the most limited definition of positive colonoscopy, DeeP-C, FDR was 71.9% for mt-sDNA + and 81.7% for FIT +. Using the USMSTF definition, FDR decreased substantially: mt-sDNA+:33.2% and FIT+:47.6%. Adding all CSSPs resulted in the lowest FDR: mt-sDNA+:32.2% and FIT+:47.1%. Decreasing FDRs corresponded to increasing PPVs: mt-sDNA+:28.1% and FIT+:18.3% (DeeP-C definition) and mt-sDNA+:67.8% and FIT+:52.9% (DeeP-C + USMSTF + CSSP) (Table 1). FDRs decreased substantially when the definition of positive exams included all significant precancerous findings. These data present a comprehensive understanding of false positive outcomes at colonoscopies following positive stool tests, which to our knowledge is the first such analysis.

Serrated Polyp Yield at Colonoscopy in Patients with Positive FIT, Positive mt-sDNA, and Colonoscopy Only: Data from the New Hampshire Colonoscopy Registry.

BACKGROUND: Stool-based screening with fecal immunochemical (FIT) or multitarget-stool DNA (mt-sDNA) tests is associated with increased colonoscopy polyp yield. mt-sDNA includes methylated markers, which improve detection of serrated polyps (SP) versus FIT. We compared SP detection in colonoscopies performed for positive FIT or mt-sDNA tests, as well as in colonoscopies without a preceding stool test, using the New Hampshire Colonoscopy Registry, a comprehensive statewide population-based registry. METHODS: Across the three groups, we compared the frequency of clinically relevant SPs (CRSP: sessile SPs, hyperplastic polyps ≥10 mm, and traditional serrated adenomas). We also compared SP size, histology, number, and bulk (combined sizes). RESULTS: Our sample included 560 mt-sDNA+ (age ± SD: 66.5 ± 7.9), 414 FIT+ (age ± SD: 66.3 ± 8.8), and 59,438 colonoscopy-only patients (age ± SD: 61.7 ± 8.0). mt-sDNA+ patients were more likely to have a higher yield of CRSPs and CRSP bulk than FIT+ (P < 0.0001) or colonoscopy-only patients (P < 0.0001). More mt-sDNA+ patients had CRSPs without large adenomas or colorectal cancers (17.9% vs. 9.9% of FIT+ and 8% of colonoscopy-only patients). After adjusting for synchronous large adenomas, colorectal cancers, and other risk factors, mt-sDNA+ patients were more likely (OR, 1.82; 95% CI, 1.18-2.85) than FIT+ patients to have CRSPs. CONCLUSIONS: mt-sDNA+ patients had a higher SP yield than FIT+ or colonoscopy-only patients, particularly in the absence of synchronous large adenomas or colorectal cancer. IMPACT: Our results suggest that screening with mt-sDNA tests could improve colorectal cancer screening by identifying more patients at increased risk from the serrated pathway.

Colorectal cancer outcomes after screening with the multi-target stool DNA assay: protocol for a large-scale, prospective cohort study (the Voyage study).

Introduction: Population-level screening has been shown to reduce the incidence and mortality of colorectal cancer (CRC). Unfortunately, adherence to screening recommendations among eligible US adults remains below national goals. A relatively new non-invasive screening modality, the Food and Drug Administration-approved multi-target stool DNA (mt-sDNA) assay (commercialised as Cologuard), which combines the detection of haemoglobin and DNA abnormalities, has been completed by more than 3 million individuals. Given mt-sDNA's recent availability, the effectiveness of mt-sDNA screening with respect to CRC incidence and mortality reduction has not yet been established. Methods and analysis: Through an academic-industry collaboration, a prospective cohort study (Voyage) was designed with an initial enrolment target of 150 000 individuals with mt-sDNA ordered by their healthcare provider for CRC screening. Consented participants will be asked to complete a baseline questionnaire to collect sociodemographic and health information. Additional questionnaires will be provided after 1 year, and every 3 years thereafter, to collect data regarding CRC screening follow-up in order to estimate rates of CRC incidence and other health outcomes. Linkage to the National Death Index will be used to estimate mortality rates. Ethics and dissemination: The Voyage study will be conducted in accordance with international guidelines and local regulatory requirements and laws. Data will be stored and retained at Mayo Clinic. Only limited data elements required for research purposes will be transmitted between Mayo Clinic and Exact Sciences Laboratories. Results of the Voyage study will be disseminated through scientific presentations and publications. Trial registration number: NCT04124406.