Faculty Bibliography

AIM/UNASSIGNED:Inadequate adherence to colorectal cancer screening reduces individual and population level health benefits. Blood-based tests offer a new modality that may help patients overcome barriers, but there are concerns about the impact of patients switching from existing guideline-recommended screening modalities. This study estimates the population health outcomes and cost-effectiveness of offering blood-based testing using a validated individual-level simulation model based on patient preference evidence from randomized controlled trials. MATERIALS AND METHODS/UNASSIGNED:In this study, a validated discrete-event simulation model was used to evaluate the performance of different combinations of colorectal cancer screening strategy preferences per 10,000 screened individuals beginning at age 45. Preferences for screening options were informed by randomized controlled trials of patients with and without the option of blood-based testing. Adherence to initial patient preferences over a simulated lifetime was modeled as: (1) assumed 100% adherence and (2) longitudinal using a calibrated model. Simulated outcomes included clinical outcomes and cost-effectiveness from a healthcare sector perspective. A strategy was deemed cost-effective at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year gained. RESULTS/UNASSIGNED:The introduction of blood-based testing to an unscreened population with evidence from randomized controlled trials is projected to increase colorectal cancer deaths averted by 35% to 116% and from 68% to 247% relative to no screening, for stated preference and revealed preference scenarios, respectively. These outcomes are cost-effective, with incremental cost-effectiveness ratios ranging from $63,994 to $85,497 and from $30,464 to $54,764 across stated preference and revealed preference scenarios, respectively. LIMITATIONS/UNASSIGNED:Given limited data, natural history and real-world longitudinal adherence to screening are based on evidence-informed assumptions. CONCLUSIONS/UNASSIGNED:Using a simulation model to extrapolate data from two recent trials, we demonstrate that the introduction of blood-based tests has the potential to lead to cost-effective increases in the number of CRC deaths averted among the unscreened population.

BACKGROUND:Emerging blood tests may improve colorectal cancer (CRC) screening uptake and outcomes but are less sensitive for advanced precancerous lesions than some currently recommended tests. We examine whether these tests meet expectations for U.S. Preventive Services Task Force (USPSTF) recommendation. METHODS:A decision-analytic model that informed USPSTF was replicated and used to estimate the lifetime benefits (averted CRC cases & deaths, life-years gained [LYG]), burdens (required screening tests & colonoscopies), and harms (colonoscopy-related complications) for annual, biennial or triennial blood testing through age 45-75 years vs a benchmark of recommended and contemporary stool-based strategies, with colonoscopy screening as the reference. Base-case analyses assumed 100% adherence. Sensitivity analyses evaluated more realistic scenarios. RESULTS:Among benchmark strategies, colonoscopy screening had the most benefit, with an estimated 30 CRC deaths averted, 356 LYG, 4270 colonoscopies required and 15 complications per 1000 adults; stool-based strategies resulted in 81-88% of LYG for colonoscopy, 6829-19,476 screening tests, 1523-1880 colonoscopies, and 9-10 complications. By comparison, annual blood testing resulted in 85-87% of LYG for colonoscopy and an intermediate number of screenings, colonoscopies and complications. Biennial and triennial blood testing provided 57-72% of LYG for colonoscopy but resulted in net population benefit under plausible scenarios for increased utilization vs existing strategies. CONCLUSIONS:The estimated benefits, burdens and harms of annual blood testing are within the range of current CRC screening strategies. Biennial and triennial testing should also be considered for recommendation given potential for increased utilization and net population benefit.

Colorectal cancer (CRC) screening uptake in the Veterans Health Administration (VA) has been reported to be higher than the US general population, but CRC remains a prevalent cancer within the VA system. To examine CRC predictors and the extent to which the conventional definition of up-to-date screening applies to the population, we conducted a case-control study using VA data from 2012 to 2018. We classified patients into 5 categories: up-to-date or not up-to-date average-risk patients aged 50 to 75 (Categories 1 and 2), up-to-date or not up-to-date average-risk patients aged <50 or >75 (Categories 3 and 4), and high-risk patients (Category 5). Each CRC case was matched by age, sex, and facility with 4 controls. We performed multivariable conditional logistic regression, adjusting for race and ethnicity, diabetes, obesity, and alcohol use. Among 3714 CRC cases identified, Category 4 (odds ratio [OR] 1.40, 95% CI 1.11-1.78) and Category 5 (OR 6.23, 95% CI 5.06-7.66) patients had a higher risk of CRC compared to Category 1 patients. Compared with White patients, Black patients had a higher risk (OR 1.54, 95% CI 1.37-1.73). Diabetes (OR 1.65, 95% CI 1.51-1.81) and alcohol use disorder (OR 1.53, 95% CI 1.35-1.73) were also associated with CRC. Most CRC cases occurred in individuals aged 50 to 75, but 12.5% occurred in persons who were outside of this age range or had high-risk personal or family history. The conventional measure of CRC screening, focused on average-risk individuals aged 50 to 75, does not reflect screening status in an important minority of CRC patients.

IMPORTANCE/UNASSIGNED:Colorectal cancer screening is widely recommended but underused. Blood-based screening offers the potential for higher adherence compared with endoscopy or stool-based testing but must first be clinically validated in a screening population. OBJECTIVE/UNASSIGNED:To evaluate the clinical performance of an investigational blood-based circulating tumor DNA test for colorectal cancer detection in an average-risk population using colonoscopy with histopathology as the reference method. DESIGN, SETTING, AND PARTICIPANTS/UNASSIGNED:Prospective, multicenter, cross-sectional observational study enrolling participants between May 2020 and April 2022 who were asymptomatic adults aged 45 to 85 years, at average risk of colorectal cancer, and willing to undergo a standard-of-care screening colonoscopy. Participants, staff, and pathologists were blinded to blood test results, and laboratory testing was performed blinded to colonoscopy findings. The study was conducted at 201 centers across 49 US states and the United Arab Emirates. Site-based and mobile phlebotomy were used for blood collection. EXPOSURES/UNASSIGNED:Participants were required to complete a screening colonoscopy after blood collection. MAIN OUTCOMES AND MEASURES/UNASSIGNED:The primary end points were sensitivity for colorectal cancer, specificity for advanced colorectal neoplasia (colorectal cancer or advanced precancerous lesions), negative predictive value for advanced colorectal neoplasia, and positive predictive value for advanced colorectal neoplasia. The secondary end point was sensitivity for advanced precancerous lesions. RESULTS/UNASSIGNED:The median age of participants in the evaluable cohort (n = 27 010) was 57.0 years, and 55.8% were women. Sensitivity for colorectal cancer was 79.2% (57/72; 95% CI, 68.4%-86.9%) and specificity for advanced colorectal neoplasia was 91.5% (22 306/24 371; 95% CI, 91.2%-91.9%). The negative predictive value for advanced colorectal neoplasia was 90.8% (22 306/24 567; 95% CI, 90.7%-90.9%) and the positive predictive value for advanced colorectal neoplasia was 15.5% (378/2443; 95% CI, 14.2%-16.8%). All primary end points met prespecified acceptance criteria. The sensitivity for advanced precancerous lesions was 12.5% (321/2567; 95% CI, 11.3%-13.8%), which did not meet the prespecified acceptance criterion. CONCLUSIONS AND RELEVANCE/UNASSIGNED:In an average-risk colorectal cancer screening population, a blood-based test demonstrated acceptable accuracy for colorectal cancer detection, but detection of advanced precancerous lesions remains a challenge, and ongoing efforts are needed to improve test sensitivity. TRIAL REGISTRATION/UNASSIGNED:ClinicalTrials.gov Identifier: NCT04369053.

BACKGROUND & AIMS/OBJECTIVE:This study assessed the economic and health impact of colorectal cancer (CRC) screening programs for average-risk individuals aged 45 years and older. METHODS:A 10-year Markov model simulated disease progression, comparing multitarget stool RNA test (mt-sRNA, ColoSense), two mt-sDNA tests (Cologuard and Cologuard Plus), a blood-based test (cfDNA, Shield), and a fecal immunochemical test (FIT). Clinical inputs leveraged age-weighted sensitivity and specificity from independent studies. Outcomes were compared with a colonoscopy-based program and no screening. Model calibration and validation used previously reported Cancer Intervention Surveillance Modeling Network (CISNET) models. RESULTS:Among molecular tests, mt-sRNA detected the most advanced adenomas, referred the most individuals to surveillance, and prevented the highest number of CRC cases and deaths. At real-world adherence of 60%, mt-sRNA reduced CRC cases and deaths by 1% and 14% compared with FIT; by 21% and 19% compared with mt-sDNA; by 28% and 23% compared with mt-sDNA+; and by 80% and 86% compared with cfDNA. For all adherence levels, FIT ($25/test) was the most cost-effective strategy. For triennial molecular tests ($509/test), mt-sRNA was the most cost-effective strategy. Relative to the mt-sRNA program, the cost to prevent a CRC case was 30% (mt-sDNA), 45% (mt-sDNA+), and 642% (cfDNA) more expensive. Relative to the mt-sRNA program, the cost to prevent a CRC death was 30% (mt-sDNA), 41% (mt-sDNA+), and 1040% (cfDNA) more expensive. CONCLUSIONS:FIT was the most cost-effective strategy for preventing CRC cases and deaths. At real-world adherence of 60%, mt-sRNA demonstrated the greatest clinical benefit and was more cost-effective than other molecular strategies.

BACKGROUND & AIMS/OBJECTIVE:This American Gastroenterological Association (AGA) guideline is intended to provide an overview of the evidence and support endoscopists and patients on the use of computer-aided detection (CADe) systems for the detection of colorectal polyps during colonoscopy. METHODS:A multidisciplinary panel of content experts and guideline methodologists used the Grading of Recommendations Assessment, Development and Evaluation framework and relied on the following sources of evidence: (1) a systematic review examining the desirable and undesirable effects (ie, benefits and harms) of CADe-assisted colonoscopy, (2) a microsimulation study estimating the effects of CADe on longer-term patient-important outcomes, (3) a systematic search of evidence evaluating the values and preferences of patients undergoing colonoscopy, and (4) a systematic review of studies evaluating health care providers' trust in artificial intelligence technology in gastroenterology. RESULTS:The panel reached the conclusion that no recommendation could be made for or against the use of CADe-assisted colonoscopy in light of very low certainty of evidence for the critical outcomes, desirable and undesirable (11 fewer colorectal cancers per 10,000 individuals and 2 fewer colorectal cancer deaths per 10,000 individuals), increased burden of more intensive surveillance colonoscopies (635 more per 10,000 individuals), and cost and resource implications. The panel acknowledged the 8% (95% CI, 6%-10%) increase in adenoma detection rate and 2% (95% CI, 0%-4%) increase in advanced adenoma and/or sessile serrated lesion detection rate. CONCLUSIONS:This guideline highlights the close tradeoff between desirable and undesirable effects and the limitations in the current evidence to support a recommendation. The panel acknowledged the potential for CADe to continually improve as an iterative artificial intelligence application. Ongoing publications providing evidence for critical outcomes will help inform a future recommendation.

INTRODUCTION/BACKGROUND:Colorectal cancer (CRC) screening rates are lower among immigrant populations in the United States (US) than the general population. Immigrant communities face structural barriers that disincentivize their engagement from CRC screening. A growing body of literature has evaluated the effects of interventions aimed at increasing CRC screening engagement among various immigrant groups, but there has not yet been a systematic synthesis of this literature. OBJECTIVE:This review will systematically evaluate quantitative studies assessing the effects of interventions designed to increase CRC screening rates among immigrant populations residing in the US. METHODS:We will conduct a comprehensive search of English language peer-reviewed and grey literature using specific keywords and database-specific structured vocabulary on interventions to improve CRC screening rates among immigrants published in 7 databases (PubMed, Cochrane Library (Wiley), CINAHL (EBSCO), ClinicalTrials.gov, Embase (Ovid), Scopus (Elsevier), and Web of Science) from January 1, 2000 to December 31, 2024. All studies will be imported into Covidence. Two reviewers will independently screen titles, abstracts, and full-texts for inclusion and exclusion criteria. Pilot screenings and consensus discussions will ensure accuracy and agreement in study selection and data extraction. Iterative data extraction of eligible studies will include critical appraisal using the Risk of Bias 2 (ROB2) for randomized controlled trials, while other study designs will be appraised with the risk of bias in nonrandomized studies of interventions (ROBINS-I) tool. Data synthesis will disaggregate pooled effect estimates by ethnicity, to the extent possible. The study protocol was pre-registered in International Prospective Register of Systematic reviews (PROSPERO): CRD42023488183. EXPECTED OUTPUTS/UNASSIGNED:This systematic review aims to generate an exhaustive summary of the evidence base, including a description of the intervention methods and settings, target populations, recruitment and retention strategies, partnerships and collaborations, and reported outcomes. The results will provide actionable recommendations for public health practitioners, healthcare providers, and policymakers developing tailored interventions and policies aimed at improving CRC screening uptake among diverse immigrant populations in the US.

BACKGROUND:Asian Americans have the lowest colorectal cancer screening uptake of any racial and ethnic group in the United States. Asian Indians are among the most under-screened Asian American subgroups, but there is limited data for this population. We sought to characterize predictors of colonoscopy use among Asian Indians in New York City. METHODS:Using 2003 to 2016 data from the New York City Community Health Survey, we identified all Asian Indian participants aged 50 years or older. We examined the association between sociodemographic and medical factors and up-to-date colonoscopy use (defined as colonoscopy within the last 10 y) using logistic regression over 4 time periods: 2003 to 2008, 2009 to 2012, 2013 to 2014, 2015 to 2016. RESULTS:On multivariable analysis, language, age, income, recent exercise, body mass index, and influenza vaccination were associated with colonoscopy uptake in 1 time period. Compared with participants who preferred English, those who preferred an Indian language were less likely to have been up-to-date in 2013 to 2014 (odds ratio 0.12, 95% CI 0.02-0.66). Individuals older than 65 years were more likely than those aged 50 to 64 years to have received a colonoscopy in 2009 to 2012 (odds ratio 3.91, 95% CI 1.49-10.24), although the risk estimates were also consistently positive in the other 3 time periods. CONCLUSIONS:Among Asian Indians living in New York City, several demographic, socioeconomic, and health-related characteristics predict colonoscopy use. These findings highlight the importance of examining determinants of colonoscopy uptake in this understudied population to inform future public health interventions.

Colorectal cancer (CRC) is the third most common cancer in the United States.¹ Although CRC incidence has declined in individuals >50 years, incidence is rising in adults <50 years (early onset).¹ By 2027, CRC is projected to become the leading cause of cancer mortality in US adults <50 years.² To combat the rising incidence of early onset CRC (EOCRC), national guidelines recently lowered the screening age from 50 to 45 years for average-risk individuals.³ Understanding the risk profile of EOCRC can help combat the rising burden in young adults, especially in those ineligible for screening.