The Development of a Digital Patient Navigation Tool to Increase Colorectal Cancer Screening Among Federally Qualified Health Center Patients: Acceptability and Usability Testing.

BACKGROUND: Federally Qualified Health Centers (FQHCs) are an essential place for historically underserved patients to access health care, including screening for colorectal cancer (CRC), one of the leading causes of cancer death in the United States. Novel interventions aimed at increasing CRC screening completion rates at FQHCs are crucial. OBJECTIVE: This study conducts user testing of a digital patient navigation tool, called eNav, designed to support FQHC patients in preparing for, requesting, and completing CRC screening tests. METHODS: We recruited English- and Spanish-speaking patients (N=20) at an FQHC in New York City to user-test the eNav website (2 user tests; n=10 participants per user test). In each user test, participants engaged in a "think aloud" exercise and a qualitative interview to summarize and review their feedback. They also completed a baseline questionnaire gathering data about demographics, technology and internet use, medical history, and health literacy, and completed surveys to assess the website's acceptability and usability. Based on participant feedback from the first user test, we modified the eNav website for a second round of testing. Then, feedback from the second user test was used to modify and finalize the eNav website. RESULTS: Survey results supported the overall usability and acceptability of the website. The average System Usability Scale score for our first user test was 75.25; for the second, it was 75.28. The average Acceptability E-scale score for our first user test was 28.3; for the second, it was 29.2. These scores meet suggested benchmarks for usability and acceptability. During qualitative think-aloud exercises, in both user tests, many participants favorably perceived the website as motivating, interesting, informative, and user-friendly. Respondents also gave suggestions on how to improve the website's content, usability, accessibility, and appeal. We found that some participants did not have the digital devices or internet access needed to interact with the eNav website at home. CONCLUSIONS: Based on participant feedback on the eNav website and reported limitations to digital access across both user tests, we made modifications to the content and design of the website. We also designed alternative methods of engagement with eNav to increase the tool's usability, accessibility, and impact for patients with diverse needs, including those with limited access to devices or the internet at home. Next, we will test the eNav intervention in a randomized controlled trial to evaluate the efficacy of the eNav website for improving CRC screening uptake among patients treated at FQHCs.

Demographic Comparison of the Burden of Endoscopically Screenable Cancers in the United States.

Background and Aims: Gastrointestinal cancer incidence varies by race and ethnicity. In the United States (US), there are screening guidelines for esophageal cancer (EC) and colorectal cancer (CRC), but not gastric cancer (GC). We compared GC, CRC, and EC incidence among the most populous racial and ethnic groups to inform US interception strategies. Methods: We used SEER∗Stat to compare GC, CRC, and EC incidence rates across non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 8 largest Asian American populations using the Surveillance, Epidemiology, and End Results 9 registries (2010-2014). Results: Noncardia GC incidence was highest among Korean (18.7 cases per 100,000) and lowest among NHW (1.4 cases per 100,000) Americans. CRC incidence was highest among non-Hispanic Black, Southeast Asian, and Japanese (35.9, 34.2, and 33.8 per 100,000, respectively) Americans and lowest among South Asian Americans (18.9 per 100,000). EC incidence was greatest in NHW (4.7 per 100,000) and lowest in Filipino (1.2 per 100,000) Americans. The incidence of noncardia GC slightly exceeded colon cancer in Korean American men (25.5 vs 22.4 per 100,000). GC surpassed EC incidence in all non-White racial and ethnic groups. Conclusion: The burden of GC, CRC, and EC differs based on race and ethnicity. Non-White racial and ethnic groups experience a disproportionate burden of GC for which systematic programs for cancer interception, similar to CRC and EC, are needed.

Endoscopic Surveillance of Gastric Intestinal Metaplasia: A Retrospective Cohort Study.

BACKGROUND: Gastric intestinal metaplasia (GIM) is a precancerous condition. Limited data exist on real-world clinical practice relative to guidelines. AIM: The aim of this study was to evaluate adherence to GIM risk stratification and identify factors associated with follow-up endoscopy. MATERIALS AND METHODS: We conducted manual chart review of patients with histologically confirmed GIM at an urban, tertiary medical center were identified retrospectively and details of their demographics, Helicobacter pylori, biopsy protocol, endoscopic/histologic findings, and postendoscopy follow-up were recorded. Multivariable logistic regression was used to identify factors independently associated with follow-up endoscopy. RESULTS: Among 253 patients, 59% were female, 37% non-Hispanic White (NHW), 26% Hispanic, 16% non-Hispanic Black (NHB). The median age at index endoscopy was 63.4 years (IQR: 55.9 to 70.0), with median follow-up of 65.1 months (IQR: 44.0 to 72.3). H. pylori was detected in 21.6% patients at index EGD. GIM extent and subtype data were frequently missing (22.9% and 32.8%, respectively). Based on available data, 26% had corpus-extended GIM and 28% had incomplete/mixed-type GIM. Compared with NHW, Hispanic patients had higher odds of follow-up EGD (OR=2.48, 95% CI: 1.23-5.01), while NHB patients had 59% lower odds of follow-up EGD (OR=0.41, 95% CI: 0.18-0.96). Corpus-extended GIM versus limited GIM (OR=2.27, 95% CI: 1.13-4.59) was associated with follow-up EGD, but GIM subtype and family history of gastric cancer were not. CONCLUSIONS: We observed suboptimal risk stratification among patients with GIM and notable race and ethnic disparities with respect to endoscopic surveillance. Targeted interventions are needed to improve practice patterns and mitigate observed disparities.

AGA Clinical Practice Update on Management of Inflammatory Bowel Disease in Patients With Malignancy: Commentary.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) Commentary is to discuss the risks of various malignancies in patients with inflammatory bowel diseases (IBD) and the impact of the available medical therapies on these risks. The CPU will also guide the approach to the patient with IBD who develops a malignancy or the patient with a history of cancer in terms of IBD medication management. METHODS: This CPU was commissioned and approved by the AGA Institute CPU committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the CPU committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology. This communication incorporates important and recently published studies in the field, and it reflects the experiences of the authors who are experts in the diagnosis and management of IBD.

Safety of Immunosuppression in a Prospective Cohort of Inflammatory Bowel Disease Patients With a HIstoRy of CancEr: SAPPHIRE Registry.

BACKGROUND & AIMS: In patients with inflammatory bowel disease (IBD) and a history of cancer, retrospective studies have suggested that exposure to immunosuppressive agents does not increase the risk of incident (recurrent or new) cancer compared with unexposed patients. SAPPHIRE is a prospective registry aimed at addressing this issue. METHODS: Since 2016, patients with IBD and confirmed index cancer before enrollment were followed up annually. Patients receiving chemotherapy or radiation at enrollment, or recurrent cancer within 5 years, were excluded. The primary outcome was development of incident cancer related to exposure to immunosuppressive medications. RESULTS: Among 305 patients (47% male, 88% white), the median age at IBD diagnosis and cancer were 32 and 52 years, respectively. Index cancers were solid organ (46%), dermatologic (32%), gastrointestinal (13%), and hematologic (9%). During a median follow-up period of 4.8 years, 210 patients (69%) were exposed to immunosuppressive therapy and 46 patients (15%) developed incident cancers (25 new, 21 recurrent). In unadjusted analysis, the crude rate of incident cancer in unexposed patients was 2.58 per 100 person-years vs 4.78 per 100 person-years (relative risk, 1.85; 95% CI, 0.92-3.73) for immunosuppression-exposed patients. In a proportional hazards model adjusting for sex, smoking history, age and stage at index malignancy, and nonmelanoma skin cancer, no significant association was found between receipt of immunosuppression and incident cancer (adjusted hazard ratio, 1.41; 95% CI, 0.69-2.90), or with any major drug class. CONCLUSIONS: In this interim analysis of patients with IBD and a history of cancer, despite numerically increased adjusted hazard ratios, we did not find a statistically significant association between subsequent exposure to immunosuppressive therapies and development of incident cancers.

Dynamic Prediction of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease.

BACKGROUND & AIMS: Colonoscopic surveillance is recommended in patients with colonic inflammatory bowel disease (IBD) given their increased risk of colorectal cancer (CRC). We aimed to develop and validate a dynamic prediction model for the occurrence of advanced colorectal neoplasia (aCRN, including high-grade dysplasia and CRC) in IBD. METHODS: We pooled data from 6 existing cohort studies from Canada, The Netherlands, the United Kingdom, and the United States. Patients with IBD and an indication for CRC surveillance were included if they underwent at least 1 follow-up procedure. Exclusion criteria included prior aCRN, prior colectomy, or an unclear indication for surveillance. Predictor variables were selected based on the literature. A dynamic prediction model was developed using a landmarking approach based on Cox proportional hazard modeling. Model performance was assessed with Harrell's concordance-statistic (discrimination) and by calibration curves. Generalizability across surveillance cohorts was evaluated by internal-external cross-validation. RESULTS: The surveillance cohorts comprised 3731 patients, enrolled and followed-up in the time period from 1973 to 2021, with a median follow-up period of 5.7 years (26,336 patient-years of follow-up evaluation); 146 individuals were diagnosed with aCRN. The model contained 8 predictors, with a cross-validation median concordance statistic of 0.74 and 0.75 for a 5- and 10-year prediction window, respectively. Calibration plots showed good calibration. Internal-external cross-validation results showed medium discrimination and reasonable to good calibration. CONCLUSIONS: The new prediction model showed good discrimination and calibration, however, generalizability results varied. Future research should focus on formal external validation and relate predicted aCRN risks to surveillance intervals before clinical application.

Pathology and Clinical Significance of Inflammatory Bowel Disease-Associated Colorectal Dysplastic Lesions.

Timely diagnosis and effective management of colorectal dysplasia play a vital role in preventing mortality from colorectal cancer in patients with chronic inflammatory bowel disease. This review provides a contemporary overview of the pathologic and endoscopic classification of dysplasia in inflammatory bowel disease, their roles in determining surveillance and management algorithms, and emerging diagnostic and therapeutic approaches that might further enhance patient management.

Molecular mechanisms in colitis-associated colorectal cancer.

Sustained chronic inflammation of the large intestine leads to tissue damage and repair, which is associated with an increased incidence of colitis-associated colorectal cancer (CAC). The genetic makeup of CAC is somewhat similar to sporadic colorectal carcinoma (sCRC), but there are differences in the sequence and timing of alterations in the carcinogenesis process. Several models have been developed to explain the development of CAC, particularly the "field cancerization" model, which proposes that chronic inflammation accelerates mutagenesis and selects for the clonal expansion of phenotypically normal, pro-tumorigenic cells. In contrast, the "Big Bang" model posits that tumorigenic clones with multiple driver gene mutations emerge spontaneously. The details of CAC tumorigenesis-and how they differ from sCRC-are not yet fully understood. In this Review, we discuss recent genetic, epigenetic, and environmental findings related to CAC pathogenesis in the past five years, with a focus on unbiased, high-resolution genetic profiling of non-dysplastic field cancerization in the context of inflammatory bowel disease (IBD).

An efficient strategy for evaluating new non-invasive screening tests for colorectal cancer: the guiding principles.

OBJECTIVE: New screening tests for colorectal cancer (CRC) are rapidly emerging. Conducting trials with mortality reduction as the end point supporting their adoption is challenging. We re-examined the principles underlying evaluation of new non-invasive tests in view of technological developments and identification of new biomarkers. DESIGN: A formal consensus approach involving a multidisciplinary expert panel revised eight previously established principles. RESULTS: Twelve newly stated principles emerged. Effectiveness of a new test can be evaluated by comparison with a proven comparator non-invasive test. The faecal immunochemical test is now considered the appropriate comparator, while colonoscopy remains the diagnostic standard. For a new test to be able to meet differing screening goals and regulatory requirements, flexibility to adjust its positivity threshold is desirable. A rigorous and efficient four-phased approach is proposed, commencing with small studies assessing the test's ability to discriminate between CRC and non-cancer states (phase I), followed by prospective estimation of accuracy across the continuum of neoplastic lesions in neoplasia-enriched populations (phase II). If these show promise, a provisional test positivity threshold is set before evaluation in typical screening populations. Phase III prospective studies determine single round intention-to-screen programme outcomes and confirm the test positivity threshold. Phase IV studies involve evaluation over repeated screening rounds with monitoring for missed lesions. Phases III and IV findings will provide the real-world data required to model test impact on CRC mortality and incidence. CONCLUSION: New non-invasive tests can be efficiently evaluated by a rigorous phased comparative approach, generating data from unbiased populations that inform predictions of their health impact.

Antigen-driven colonic inflammation is associated with development of dysplasia in primary sclerosing cholangitis.

Primary sclerosing cholangitis (PSC) is an immune-mediated disease of the bile ducts that co-occurs with inflammatory bowel disease (IBD) in almost 90% of cases. Colorectal cancer is a major complication of patients with PSC and IBD, and these patients are at a much greater risk compared to patients with IBD without concomitant PSC. Combining flow cytometry, bulk and single-cell transcriptomics, and T and B cell receptor repertoire analysis of right colon tissue from 65 patients with PSC, 108 patients with IBD and 48 healthy individuals we identified a unique adaptive inflammatory transcriptional signature associated with greater risk and shorter time to dysplasia in patients with PSC. This inflammatory signature is characterized by antigen-driven interleukin-17A (IL-17A)+ forkhead box P3 (FOXP3)+ CD4 T cells that express a pathogenic IL-17 signature, as well as an expansion of IgG-secreting plasma cells. These results suggest that the mechanisms that drive the emergence of dysplasia in PSC and IBD are distinct and provide molecular insights that could guide prevention of colorectal cancer in individuals with PSC.

Assessment of Stool DNA Markers to Detect Colorectal Neoplasia in Patients with Inflammatory Bowel Disease: A Multi-site Case-control Study.

BACKGROUND AND AIMS: The FDA-approved multitarget stool-DNA [mt-sDNA] test is a successful colorectal cancer [CRC] screening tool in average-risk individuals but is not indicated for patients with inflammatory bowel disease [IBD]. We determined the performance of the mt-sDNA assay without the haemoglobin component [mt-sDNAHgb-] in patients with IBD, while measuring sensitivity for colorectal cancer and advanced colorectal neoplasia [ACRN]. METHODS: This was a multi-centre, proof-of-concept investigation in persons aged 18-84 years with a diagnosis of IBD, or primary sclerosing cholangitis [PSC] with IBD. Enrolment occurred between March 2013 and May 2016. Stool was tested with the mt-sDNA molecular markers only, minus the immunochemical haemoglobin component. RESULTS: The analysis set contained 355 samples. The median age was 52 [range 39-62] years, 45.6% were female and 93% were White. Two-thirds [63%] had ulcerative colitis [UC] and 10.1% had PSC/IBD. Colonoscopy revealed cancer in 8.5% [N = 30], advanced precancerous lesions [APLs] in 9.3% [N = 33] and non-advanced precancerous lesions in 7.6% [N = 27], and three-quarters [74.7%, N = 265] had negative findings. mt-sDNAHgb- sensitivity was 73.3% for any stage cancers, and 76.2% for ACRN. Sensitivity was highest for IBD-associated high-grade dysplasia at 100% and 84.6% for IBD-associated low-grade dysplasia ≥1 cm. The test showed higher sensitivity and lower specificity in UC than in Crohn's disease. Increasing inflammation score was associated with a significant decrease in mt-sDNAHgb- test score [ = 0.028] amongst neoplasia-negative individuals, but not in patients with ACRN. CONCLUSIONS: These data highlight the potential of multitarget stool-DNA marker testing as an important addition to colorectal cancer surveillance by complementing colonoscopic evaluations in IBD patients.

Epidemiology of Gastric Malignancies 2000-2018 According to Histology: A Population-Based Analysis of Incidence and Temporal Trends.

BACKGROUND & AIMS: Gastric cancer (GC) remains a leading cause of cancer and cancer-related mortality. Recent reports suggest noncardia GC is increasing in certain U.S. POPULATIONS: However, whether these trends are driven by gastric adenocarcinoma (GA) or other histologies, including neuroendocrine tumors (NETs), lymphoma, or gastrointestinal stromal tumors (GISTs), is unclear. METHODS: We analyzed the Surveillance, Epidemiology and End Results-18 cancer registry (2000-2018) to determine age-standardized incidence rates (ASIR) and annual percentage change (APC) trends for histologically-confirmed GCs, stratified by anatomic location (noncardia vs cardia), age group (20-49 vs 50+ years), sex, race, and ethnicity. Joinpoint regression modeling estimated the statistical significance of trend comparisons. RESULTS: Of 74,520 individuals with noncardia GC, most (66.2%) were GA, with the next largest categories being non-mucosa-associated lymphoid tissue (non-MALT) lymphomas (6.9%), GIST (6.7%), NET (6.4%), and MALT lymphoma (5.6%). Noncardia GA ASIR was significantly higher than other histologies and demonstrated the greatest differences by race and ethnicity. APCs for GA and MALT, both Helicobacter pylori-associated cancers, declined significantly over time, which was driven primarily by trends among individuals ≥50 years-old. NET and GIST APCs significantly increased irrespective of age group, with the highest APCs observed among non-Hispanic white individuals. Cardia GC was rarer than noncardia GC and comprised primarily by GA (87.9%). Cardia GC incidence fell during the study period, which was primarily driven by decline in cardia GA. CONCLUSIONS: GA was the most common histology. On the basis of our findings, the rise in noncardia GC among certain U.S. populations appears predominantly driven by NET and GIST, not GA. Further studies are needed to clarify underlying etiologies for these findings.

Three-Year Interval for the Multi-Target Stool DNA Test for Colorectal Cancer Screening: A Longitudinal Study.

Data supporting the clinical utility of multi-target stool DNA (mt-sDNA) at the guideline-recommended 3-year interval have not been reported.Between April 2015 and July 2016, candidates for colorectal cancer screening whose providers prescribed the mt-sDNA test were enrolled. Participants with a positive baseline test were recommended for colonoscopy and completed the study. Those with a negative baseline test were followed annually for 3 years. In year 3, the mt-sDNA test was repeated and colonoscopy was recommended independent of results. Data were analyzed using the Predictive Summary Index (PSI), a measure of the gain in certainty for dichotomous diagnostic tests (where a positive value indicates a net gain), and by comparing observed versus expected colorectal cancers and advanced precancerous lesions.Of 2,404 enrolled subjects, 2,044 (85%) had a valid baseline mt-sDNA result [284 (13.9%) positive and 1,760 (86.1%) negative]. Following participant attrition, the year 3 intention to screen cohort included 591 of 1,760 (33.6%) subjects with valid mt-sDNA and colonoscopy results, with no colorectal cancers and 63 advanced precancerous lesions [22 (34.9%) detected by mt-sDNA] and respective PSI values of 0% (P = 1) and 9.3% (P = 0.01). The observed 3-year colorectal cancer yield was lower than expected (one-sided P = 0.09), while that for advanced precancerous lesions was higher than expected (two-sided P = 0.009).Repeat mt-sDNA screening at a 3-year interval resulted in a statistically significant gain in detection of advanced precancerous lesions. Due to absence of year 3 colorectal cancers, the PSI estimate for colorectal cancer was underpowered and could not be reliably quantified. Larger studies are required to assess the colorectal cancer study findings. PREVENTION RELEVANCE: Understanding the 3-year yield of mt-sDNA for colorectal cancer and advanced precancerous polyps is required to ensure the clinical appropriateness of the 3-year interval and to optimize mt-sDNA's screening effectiveness.

Endoscopic management of patients with high-risk colorectal colitis-associated neoplasia: a Delphi study.

BACKGROUND AND AIMS: Current guidelines recommend endoscopic resection of visible and endoscopically resectable colorectal colitis-associated neoplasia (CAN) in patients with inflammatory bowel disease (IBD). However, patients with high-risk CAN (HR-CAN) are often not amenable to conventional resection techniques, and a consensus approach for the endoscopic management of these lesions is presently lacking. This Delphi study aims to reach consensus among experts on the endoscopic management of these lesions. METHODS: A 3-round modified Delphi process was conducted to reach consensus among worldwide IBD and/or endoscopy experts (n = 18) from 3 continents. Consensus was considered if ≥75% agreed or disagreed. Quality of evidence was assessed by the criteria of the Cochrane Collaboration group. RESULTS: Consensus was reached on all statements (n = 14). Experts agreed on a definition for CAN and HR-CAN. Consensus was reached on the examination of the colon with enhanced endoscopic imaging before resection, the endoscopic resectability of an HR-CAN lesion, and endoscopic assessment and standard report of CAN lesions. In addition, experts agreed on type of resections of HR-CAN (< 20 mm, >20 mm, with or without good lifting), endoscopic success (technical success and outcomes), histologic assessment, and follow-up in HR-CAN. CONCLUSIONS: This is the first step in developing international consensus-based recommendations for endoscopic management of CAN and HR-CAN. Although the quality of available evidence was considered low, consensus was reached on several aspects of the management of CAN and HR-CAN. The present work and proposed standardization might benefit future studies.

A local tumor microenvironment acquired super-enhancer induces an oncogenic driver in colorectal carcinoma.

Tumors exhibit enhancer reprogramming compared to normal tissue. The etiology is largely attributed to cell-intrinsic genomic alterations. Here, using freshly resected primary CRC tumors and patient-matched adjacent normal colon, we find divergent epigenetic landscapes between CRC tumors and cell lines. Intriguingly, this phenomenon extends to highly recurrent aberrant super-enhancers gained in CRC over normal. We find one such super-enhancer activated in epithelial cancer cells due to surrounding inflammation in the tumor microenvironment. We restore this super-enhancer and its expressed gene, PDZK1IP1, following treatment with cytokines or xenotransplantation into nude mice, thus demonstrating cell-extrinsic etiology. We demonstrate mechanistically that PDZK1IP1 enhances the reductive capacity CRC cancer cells via the pentose phosphate pathway. We show this activation enables efficient growth under oxidative conditions, challenging the previous notion that PDZK1IP1 acts as a tumor suppressor in CRC. Collectively, these observations highlight the significance of epigenomic profiling on primary specimens.

Shifts in the Proportion of Distant Stage Early-Onset Colorectal Adenocarcinoma in the United States.

BACKGROUND: Carcinoids, frequently classified as "colorectal cancer" contribute to rising early-onset colorectal cancer (EOCRC) incidence rates (IR) and have distinct staging distributions compared to often advanced stage adenocarcinomas (screening target). Thus, assessing temporal shifts in early-onset distant stage adenocarcinoma can impact public health. METHODS: 2000-2016 Surveillance Epidemiology and End Results (SEER) 18 yearly adenocarcinoma IRs were stratified by stage (in situ, localized, regional, distant), age (20-29, 30-39, 40-49, 50-54-year-olds), subsite (colorectal, rectal-only, colon-only), and race [non-Hispanic whites, non-Hispanic Blacks (NHB), Hispanics] in 103,975 patients. Three-year average annual IR changes (pooled 2000-2002 IRs compared with 2014-2016) and cancer stage proportions (percent contribution of each cancer stage) were calculated. RESULTS: Comparing 2000-2002 with 2014-2016, the steepest percent increases are in distant stage cancers. Colon-only, distant adenocarcinoma increased most in 30-39-year-olds (49%, 0.75/100,000→1.12/100,00, P < 0.05). Rectal-only, distant stage increases were steepest in 20-29-year-olds (133%, 0.06/100,000→0.14/100,000, P < 0.05), followed by 30-39-year-olds (97%, 0.39/100,000→0.77/100,000, P < 0.05) and 40-49-year-olds (48%, 1.38/100,000→2.04/100,000, P < 0.05). Distant stage proportions (2000-2002 to 2014-2016) increased for colon-only and rectal-only subsites in young patients with the largest increases for rectal-only in 20-29-year-olds (18%→31%) and 30-39-year-olds (20%→29%). By race, distant stage proportion increases were largest for rectal-only in 20-29-year-old NHBs (0%→46%) and Hispanics (28%→41%). Distant colon proportion increased most in 20-29-year-old NHBs (20%→34%). CONCLUSIONS: Youngest patients show greatest burdens of distant colorectal adenocarcinoma. Although affecting all races, burdens are higher in NHB and Hispanic subgroups, although case counts remain relatively low. IMPACT: Optimizing earlier screening initiatives and risk-stratifying younger patients by symptoms and family history are critical to counteract rising distant stage disease.

Prevalence and Predictors of Young-Onset Colorectal Neoplasia: Insights From a Nationally Representative Colonoscopy Registry.

BACKGROUND & AIMS: A disturbing increase in early-onset colorectal cancer (EOCRC) has prompted recent guidelines to recommend lowering the colorectal cancer (CRC) screening starting age from 50 to 45 years old for average-risk individuals. Little is known about the prevalence of colorectal neoplasia in individuals between 45 and 49 years old, or even younger, in the United States. We analyzed a large, nationally representative data set of almost 3 million outpatient colonoscopies to determine the prevalence of, and risk factors for, colorectal neoplasia among patients aged 18 to 54. METHODS: Findings from high-quality colonoscopies were analyzed from AMSURG ambulatory endoscopy centers (ASCs) that report their results in the GI Quality Improvement Consortium (GIQuIC) Registry. Logistic regression was used to identify risk factors for EOCRC. RESULTS: Increasing age, male sex, White race, family history of CRC, and examinations for bleeding or screening were all associated with higher odds of advanced premalignant lesions (APLs) and CRC. Among patients aged 45 to 49, 32% had any neoplasia, 7.5% had APLs, and 0.58% had CRC. Rates were almost as high in those aged 40 to 44. Family history of CRC portended neoplasia rates 5 years earlier. Rates of APLs were higher in American Indian/Alaskan Natives, but lower among Blacks, Asians, and Hispanics, compared with White counterparts. The prevalence of any neoplasia and APL gradually increased between 2014 and 2019, in all age groups. CONCLUSIONS: These data provide support for lowering the screening age to 45 for all average-risk individuals. Early messaging to patients and providers in the years leading up to age 45 is warranted, especially in those with a family history of CRC.