Colorectal cancer (CRC) is a leading cause of morbidity and cancer-related mortality in the United States. Despite multiple screening options, adherence to CRC screening in the United States remains suboptimal, and there are racial, ethnic, and geographic disparities in CRC screening rates and outcomes. Advances in diagnostic technology have allowed for development and validation of blood tests for CRC screening. In this Clinical Practice Update, our aims were to review the current evidence on blood tests and the potential implications for CRC screening. We leveraged published modeling studies to understand the optimal test performance characteristics, interval, and uptake that would be needed for blood tests to achieve comparable effectiveness to that of currently available stool tests and screening colonoscopy.

This expert review/commentary was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership. The manuscript underwent internal peer review by the Clinical Practice Updates Committee and external peer review through standard procedures of Clinical Gastroenterology and Hepatology.

Colorectal cancer (CRC) is one of the most common malignant tumors, and early screening is crucial to improving the survival rate of patients. The combination of colonoscopy and immune fecal occult blood detection has garnered significant attention as a novel method for CRC screening. Colonoscopy and fecal occult blood tests, when combined, can improve screening accuracy and early detection rates, thereby facilitating early intervention and treatment. However, certain risks and costs accompany it, making the establishment of a risk classification model crucial for accurate classification and management of screened subjects.

To evaluate the feasibility and effectiveness of colonoscopy, immune fecal occult blood test (FIT), and risk-graded screening strategies in CRC screening.

Based on the randomized controlled trial of CRC screening in the population conducted by our hospital May 2020 to May 2023, participants who met the requirements were randomly assigned to a colonoscopy group, an FIT group, or a graded screening group at a ratio of 1:2:2 (after risk assessment, the high-risk group received colonoscopy, the low-risk group received an FIT test, and the FIT-positive group received colonoscopy). The three groups received CRC screening with different protocols, among which the colonoscopy group only received baseline screening, and the FIT group and the graded screening group received annual follow-up screening based on baseline screening. The primary outcome was the detection rate of advanced tumors, including CRC and advanced adenoma. The population participation rate, advanced tumor detection rate, and colonoscopy load of the three screening programs were compared.

A total of 19373 subjects who met the inclusion and exclusion criteria were enrolled, including 8082 males (41.7%) and 11291 females (58.3%). The mean age was 60.05 ± 6.5 years. Among them, 3883 patients were enrolled in the colonoscopy group, 7793 in the FIT group, and 7697 in the graded screening group. Two rounds of follow-up screening were completed in the FIT group and the graded screening group. The graded screening group (89.2%) and the colonoscopy group (42.3%) had the lowest overall screening participation rates, while the FIT group had the highest (99.3%). The results of the intentional analysis showed that the detection rate of advanced tumors in the colonoscopy group was greater than that of the FIT group [2.76% vs 2.17%, odds ratio (OR) = 1.30, 95% confidence interval (CI): 1.01-1.65, P = 0.037]. There was no significant difference in the detection rate of advanced tumors between the colonoscopy group and the graded screening group (2.76% vs 2.35%, OR = 1.9, 95%CI: 0.93-1.51, P = 0.156), as well as between the graded screening group and the FIT group (2.35% vs 2.17%, OR = 1.09%, 95%CI: 0.88-1.34, P = 0.440). The number of colonoscopy examinations required for each patient with advanced tumors was used as an index to evaluate the colonoscopy load during population screening. The graded screening group had the highest colonoscopy load (15.4 times), followed by the colonoscopy group (10.2 times), and the FIT group had the lowest (7.8 times).

A hierarchical screening strategy based on CRC risk assessment is feasible for screening for CRC in the population. It can be used as an effective supplement to traditional colonoscopy and FIT screening programs.

Residents of Appalachian regions in Kentucky experience increased colorectal cancer (CRC) incidence and mortality. While population-based screening methods, such as fecal immunochemical tests (FITs), can reduce many screening barriers, written instructions to complete FIT can be challenging for some individuals. We developed a novel audiovisual tool ("talking card") to educate and motivate accurate FIT completion and assessed its feasibility, acceptability, and efficacy.

We collected data on the talking card via: (1) cross-sectional surveys exploring perceptions of images, messaging, and perceived utility; (2) follow-up focus groups centered on feasibility and acceptability; and (3) efficacy testing in community-based FIT distribution events, where we assessed FIT completion rate, number of positive vs. negative screens, demographic characteristics of participants, and primary drivers of FIT completion.

Across the three study phases, 692 individuals participated. Survey respondents positively identified with the card's sounds and images, found it highly acceptable, and reported high-to-very high self-efficacy and response efficacy for completing FIT, with nearly half noting greater likelihood to complete screening after using the tool. Focus group participants confirmed the acceptability of the individuals featured on the card. Nearly 75% of participants provided a FIT accurately completed it, with most indicating the talking card, either alone or combined with another strategy, helped with completion.

To reduce CRC screening disparities among Appalachian Kentuckians, population-based screening using contextually relevant implementation strategies must be used alongside clinic-based education. The talking card represents a novel and promising strategy to promote screening uptake in both clinical and community settings.

Colorectal cancer (CRC) is a common malignant tumor, and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients' survival rate and quality of life. Indicators such as albumin bilirubin (ALBI) score, liver function index, and carcinoembryonic antigen (CEA) have shown some potential in the prediction of liver metastasis but have not been fully explored.

To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI, liver function index, and CEA, and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance.

This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months. According to the follow-up results, the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1. The risk factors for liver metastasis in patients with CRC were analyzed, a prediction model was constructed by least absolute shrinkage and selection operator (LASSO) logistic regression, internal validation was performed by the bootstrap method, the reliability of the prediction model was evaluated by subject-work characteristic curves, calibration curves, and clinical decision curves, and a column graph was drawn to show the prediction results.

Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria. Through LASSO regression variable screening and logistic regression analysis. The ALBI score, alanine aminotransferase (ALT), and CEA were found to be independent predictors of liver metastases in CRC patients [odds ratio (OR) = 8.062, 95% confidence interval (CI): 2.545-25.540], (OR = 1.037, 95%CI: 1.004-1.071) and (OR = 1.025, 95%CI: 1.008-1.043). The area under the receiver operating characteristic curve (AUC) for the combined prediction of CRLM in the modeling group was 0.921, with a sensitivity of 78.0% and a specificity of 95.0%. The H-index was 0.921, and the H-L fit curve had χ2 = 0.851, a P value of 0.654, and a slope of the calibration curve approaching 1. This indicates that the model is extremely accurate, and the clinical decision curve demonstrates that it can be applied effectively in the real world. We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method. The AUC was 0.913, while the accuracy was 0.869 and the kappa consistency was 0.709. The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918, sensitivity of 85.0%, specificity of 95.6%, C-index of 0.918, and an H-L fitting curve with χ 2 = 0.586, P = 0.746.

The ALBI score, ALT level, and CEA level have a certain value in predicting liver metastasis in patients with CRC. These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC. The risk prediction model developed in this work shows great potential for practical application.

Despite national policy efforts to increase colorectal cancer (CRC) screening, rates in vulnerable populations remain suboptimal. Many types of interventions have been employed, but their impact on improving population-level rates of CRC screening over time is uncertain.

Assess the impact of 10 years of different in-reach and outreach strategies to improve CRC screening and identify factors associated with being screen up-to-date (SUTD).

Observational cohort study.

Patients aged 50-74 years from 12 community-based primary care clinics in an integrated, regional safety-net health system.

Multiple system-level interventions were implemented over time (visit-based electronic health record [EHR] reminders, quality measurement, annual preventive service letters, and mailed fecal immunohistochemical stool tests [FIT]).

CRC SUTD rates by calendar year among those with a primary care (PC) visit in the prior 1 and 3 years and their multivariable correlates.

The sample included 31,786-40,405 patients/year. In 2011, mean age was 58.9, 63.9% were women, 37.0% were Hispanic, 39.3% Black, 16.8% White, and 6.6% Asian/Other, and 60.5% were uninsured/Medicaid. Three-quarters of patients had ≥ 1 PC visit in the prior year. Lower-intensity interventions (EHR reminders, quality measurement, annual prevention letters) had limited impact on SUTD rates (2-3% rise). Implementing system-wide mailed FIT increased rates from 51.2 to 61.9% among those with a PC visit in the past year (40.5 to 46.8% with a PC visit ≤ 3 years). Stopping mailed FIT due to COVID wiped out these gains. Higher screening rates were associated with the following: older age; female; more comorbidities, PC clinic visits, and prior FITs; and better insurance coverage. Hispanics had the highest SUTD rates followed by Asians, Blacks, and Whites (p < 0.05).

Implementation of a system-wide mailed FIT program had the greatest impact on SUTD rates. Lower-intensity interventions (EHR reminders, quality measurement, and patient letters) had limited effects.

Mailed fecal immunochemical test (FIT) outreach can improve colorectal cancer screening participation. We assessed the reach and effectiveness of adding notifications to mailed FIT programs.

We conducted secondary analyses of a stepped-wedge evaluation of an enhanced mailed FIT program (n = 15 clinics). Patients were stratified by prior FIT completion. Those with prior FIT were sent a text message (Group 1); those without were randomized 1:1 to receive a text message (Group 2) or live phone call (Group 3). All groups were sent automated phone call reminders. In stratified analysis, we measured reach and effectiveness (FIT completion within 6 months) and assessed patient-level associations using generalized estimating equations.

Patients (n = 16,934; 83% Latino; 72% completed prior FIT) were reached most often by text messages (78%), followed by live phone calls (71%), then automated phone calls (56%). FIT completion was higher in patients with prior FIT completion versus without [44% (Group 1) vs. 19% (Group 2 + Group 3); P < 0.01]. For patients without prior FIT, effectiveness was higher in those allocated to a live phone call [20% (Group 3) vs. 18% (Group 2) for text message; P = 0.04] and in those who personally answered the live call (28% vs. 9% no call completed; P < 0.01).

Text messages reached the most patients, yet effectiveness was highest in those who personally answered the live phone call.

Despite the broad reach and low cost of text messages, personalized approaches may more successfully boost FIT completion.

Colorectal cancer (CRC) screening reduces morbidity and mortality, but screening rates in the USA remain suboptimal. The Colorectal Cancer Control Program (CRCCP) was established in 2009 to increase screening among groups disproportionately affected. The CRCCP utilizes implementation science to support health system change as a strategy to reduce disparities in CRC screening by directing resources to primary care clinics to implement evidence-based interventions (EBIs) proven to increase CRC screening. As COVID-19 continues to impede in-person healthcare visits and compel the unpredictable redirection of clinic priorities, understanding clinics' adoption and implementation of EBIs into routine care is crucial. Mailed fecal testing is an evidence-based screening approach that offers an alternative to in-person screening tests and represents a promising approach to reduce CRC screening disparities. However, little is known about how mailed fecal testing is implemented in real-world settings. In this retrospective, cross-sectional analysis, we assessed practices around mailed fecal testing implementation in 185 clinics across 62 US health systems. We sought to (1) determine whether clinics that do and do not implement mailed fecal testing differ with respect to characteristics (e.g., type, location, and proportion of uninsured patients) and (2) identify implementation practices among clinics that offer mailed fecal testing. Our findings revealed that over half (58%) of clinics implemented mailed fecal testing. These clinics were more likely to have a CRC screening policy than clinics that did not implement mailed fecal testing (p = 0.007) and to serve a larger patient population (p = 0.004), but less likely to have a large proportion of uninsured patients (p = 0.01). Clinics that implemented mailed fecal testing offered it in combination with EBIs, including patient reminders (92%), provider reminders (94%), and other activities to reduce structural barriers (95%). However, fewer clinics reported having the leadership support (58%) or funding stability (29%) to sustain mailed fecal testing. Mailed fecal testing was widely implemented alongside other EBIs in primary care clinics participating in the CRCCP, but multiple opportunities for enhancing its implementation exist. These include increasing the proportion of community health centers/federally qualified health centers offering mailed screening; increasing the proportion that provide pre-paid return mail supplies with the screening kit; increasing the proportion of clinics monitoring both screening kit distribution and return; ensuring patients with abnormal tests can obtain colonoscopy; and increasing sustainability planning and support.

The effectiveness of mailed fecal immunochemical test outreach might be enhanced through an organized colorectal cancer screening program, yet published real-world experiences are limited. We synthesized the process of implementing a colorectal cancer screening program that used mailed fecal immunochemical test outreach in a large integrated academic-community practice.

Data from a pilot mailed fecal immunochemical test program were shared with healthcare system leadership, which inspired the creation of a cross-institutional organized colorectal cancer screening program. In partnership with a centralized population health team and primary care, we defined (1) the institutional approach to colorectal cancer screening, (2) the target population and method for screening, (3) the team responsible for implementation, (4) the healthcare team responsible for decisions and care, (5) a quality assurance structure, and (6) a method for identifying cancer occurrence.

The Fred Hutch/UW Medicine Population Health Colorectal Cancer Screening Program began in September 2021. The workflow for mailed fecal immunochemical test outreach included a mailed postcard, a MyChart message from the patient's primary care provider, a fecal immunochemical test kit with a letter signed by the primary care provider and program director, and up to 3 biweekly reminders. Patients without a colonoscopy 3 months after an abnormal fecal immunochemical test result received navigation through the program. In the first program year, we identified 9,719 patients eligible for outreach, and in an intention-to-treat analysis, 32% of patients completed colorectal cancer screening by fecal immunochemical test or colonoscopy.

Real-world experiences detailing how to implement organized colorectal cancer screening programs might increase adoption. In our experience, broadly disseminating pilot data, early institutional support, robust data management, and strong cross-departmental relationships were critical to successfully implementing a colorectal cancer screening program that benefits all patients.

Fecal immunochemical test (FIT) is an effective colorectal cancer screening modality. Little is known about prevalence, reasons, and testing after unsatisfactory FIT, or a FIT that cannot be processed by the laboratory due to inadequate stool specimen or incomplete labeling.

Our retrospective cohort study examined unsatisfactory FIT among average-risk individuals aged 50-74 years in a large, integrated, safety-net health system who completed an index FIT from 2010 to 2019. We determined prevalence of unsatisfactory FIT and categorized reasons hierarchically. We used multivariable logistic regression models to identify factors associated with: (i) unsatisfactory FIT; and (ii) subsequent testing within 15 months of the unsatisfactory FIT.

Of 56,980 individuals completing an index FIT, 10.2% had an unsatisfactory FIT. Reasons included inadequate specimen (51%), incomplete labeling (27%), old specimen (13%), and broken/leaking container (8%). Unsatisfactory FIT was associated with being male [OR, 1.10; confidence interval (CI), 1.03-1.16], Black (OR, 1.46; CI, 1.33-1.61), Spanish speaking (OR, 1.12; CI, 1.01-1.24), on Medicaid (OR, 1.42; CI, 1.28-1.58), and received FIT by mail (OR, 2.66; CI, 2.35-3.01). Among those with an unsatisfactory FIT, fewer than half (41%) completed a subsequent test within 15 months (median, 4.4 months). Adults aged 50-54 years (OR, 1.16; CI, 1.01-1.39) and those who received FIT by mail (OR, 1.92; CI, 1.49-2.09) were more likely to complete a subsequent test.

One in ten returned a FIT that could not be processed, mostly due to patient-related reasons. Fewer than half completed a subsequent test after unsatisfactory FIT.

Screening programs should address these breakdowns such as specimen collection and labeling to improve real-world effectiveness. See related In the Spotlight, p. 183.