Reduce Colorectal Cancer Mortality Research Articles

Cost-effectiveness of blood-based colorectal cancer screening: A simulation model incorporating real-world longitudinal adherence.

93 Background: Colorectal cancer (CRC) is a predominant cause of cancer-related mortality worldwide. Regular screening improves outcomes. However, despite there being many U.S. Preventive Services Task Force (USPSTF) recommended CRC screening options, many people elect not to use any of them. Most cost-effectiveness models assume perfect (100%) adherence initially and over time (longitudinally), which is implausible as approximately one-third of eligible individuals are not up to date with CRC screening. Our study evaluates the cost-effectiveness of Shield, an FDA-approved blood-based CRC test, while incorporating real-world adherence. Methods: The CAN-SCREEN (Colorectal cANcer SCReening Economics and adherENce) model is a validated, discrete-event simulation model designed to evaluate the clinical and economic outcomes of CRC screening strategies under real-world adherence scenarios. We simulated individual lifetime outcomes for a cohort of 10,000 people beginning screening at age 45, running 4,000 trials per cohort. We conducted a cost-effectiveness analysis using the CAN-SCREEN model, and compared the Shield blood-based test administered every three years to no screening. Costs were calculated from a healthcare perspective and adjusted to 2023 US dollars. Shield was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below $100,000 per quality-adjusted life-year (QALY) gained. The analysis also assessed the maximum price Shield could maintain while remaining cost-effective. Results: Compared to no screening, Shield increased the number of QALYs by 154 per 1,000 individuals and raised costs by $7.5 million per 1,000 individuals at its commercial test cost. With an incremental cost of $48,662 per QALY gained, Shield was found to be cost-effective relative to no screening at $100,000 cost per QALY willingness-to-pay threshold. Furthermore, the unit cost of Shield can be as high as $3,241 and $4,942 to be considered cost-effective at $100,000 and $150,000 per QALY gained, respectively. Conclusions: This study used the CAN-SCREEN model to compare Shield, an FDA-approved blood-based CRC screening test, against no screening, finding that Shield is cost-effective. With about one-third of the U.S. population not up to date on CRC screening, Shield's noninvasive approach offers a promising, cost-effective solution to increase adherence and reduce CRC mortality. Economic outcomes of Shield against no screening using CAN-SCREEN model. Intervention Test Unit Cost QALYs/Person Cost ($)/Person Cost ($)/QALY Gained vs No screening No Intervention - 15.269 $6,312.18 - Shield $1,495 15.423 $13,786.72 $48,662 Shield $3,241 15.423 $21,672.34 $100,000.00 Shield $4,942 15.423 $29,352.42 $150,000.00

Modeling and the Use of Surrogate Endpoints: Is This a Valid Approach?

Development of novel colorectal cancer (CRC) screening tests is a dynamic field. Decision analytic modeling based on inputs derived from rigorous prospective studies informs CRC screening guidelines. Exploratory modeling may have a place in early phases of test development. We explored whether (1) surrogate endpoints for long-term, programmatic effectiveness, and cost-effectiveness could be potentially informative in early stages of test development and (2) whether rapid exploratory modeling with a web-based tool would be feasible. First, based on comparisons with published estimates for reductions in CRC mortality with various screening tests in four established decision analytic models of CRC screening, the surrogate endpoint of the number needed to colonoscope to detect one CRC or advanced precancerous lesion (APL) in round 1 of screening appears to hold promise as a measure of clinical effectiveness. Similarly, based on comparisons with published estimates for cost/quality-adjusted life-year gained with screening in the four models, the surrogate endpoint of cost to detect one CRC or APL in round 1 of screening appears to hold promise as a measure of cost-effectiveness. Second, exploration of the impact of lowering the screening initiation age in Israel from age 50 to 45 with the web-based EU-TOPIA tool, compared with the results of a recently published comprehensive modeling study, suggests that exploratory modeling of programmatic screening may be feasible with relatively low time demand vs. that required for typical full-length modeling publications. Further validation in other models and with a broader set of test performance characteristics is prudent before surrogate endpoints or rapid modeling are incorporated into the novel test development process.

When Should Colon Cancer Screening Begin? The Impact of Early-Onset Colorectal Cancer and the Reality of an Unscreened Older Population.

Recent increases in colorectal cancer (CRC) incidence and mortality under age 50 have led the US to recommend starting screening at age 45years instead of 50. Several other countries are now also reconsidering the age to start CRC screening. To aid decision makers in making an informed decision about lowering the starting age of CRC screening in their jurisdictions. In this article, we present the clinical and modeling evidence for the optimal age to start CRC screening and provide a checklist of considerations for decisions on age to start CRC screening. Two observational studies showed that detection of advanced neoplasia in those aged 45-49years undergoing colonoscopy was at least as high as in those aged 50-54years. One Taiwanese study reported a 22% reduction in CRC incidence and a 39% reduction in CRC mortality from FIT screening in those 40-49years compared to those 50years and older. Nine modeling studies concluded that lowering the age to start screening to age 45 was cost-effective. However, lowering the start age can have negative spill-off effects, such as increased wait times for diagnostic colonoscopy for symptomatic individuals and decreased screening participation. In an effort to support decision making and prevent negative spill-off, the National Colorectal Cancer Screening Network in Canadaproposed a Worksheet to determine the resource impact of earlier screening initiation. Lowering the age to start CRC screening to 45years likely leads to a reduction in CRC incidence and mortality but requires additional healthcare resources. Policy makers can use the worksheet to assess the expected increase and assess the feasibility within their jurisdictions.

Colorectal Cancer (CRC) Screening in Occupational Health Surveillance Exams Is Associated With Decreased CRC Mortality.

Colorectal cancer (CRC) screening is recommended for adults aged 45 to 75. Using data from a national screening program, we examined the impact of CRC screening in a population with occupational exposures. Since 1998, the Building Trades National Medical Screening Program (BTMed) has offered CRC screening every 3 years. Tests used were: guaiac fecal occult blood test (gFOBT), 1998-2008; high sensitivity (HS)-gFOBT, 2009-2015; and fecal immunochemical test (FIT) since 2015. Data from the National Death Index through December 31, 2021 were used to compute standardized mortality ratios (SMRs) to compare the mortality experience of exam participants to nonparticipants. Internal analyses used Poisson regression and Cox regression to evaluation impact of CRC screening participation on CRC mortality. Participation in gFOBT was 68.2%; HS-gFOBT, 78.7%; and FIT, 85.9%. The SMR for CRC was significantly higher for BTMed exam nonparticipants (SMR = 2.04, 95% CI 1.40-2.86) than exam participants (SMR = 1.07, 95% CI 0.88-1.28). Impact of CRC screening participation on reducing CRC mortality by type of test was 2% for gFOBT, 12% for HS-FOBT, and 61% for FIT. This study found higher CRC screening participation than in the general population, with mortality reduction from screening similar to what is found in the general population, even though BTMed screening was conducted every 3 years rather than annually. Participation in CRC screening had a significant impact on CRC mortality. Innovations in stool tests have led to greater convenience, participation, and impact, particularly for the FIT test. Occupational health practices should consider including CRC screening.

How Good Is Good Enough? What Should Be the Target for CRC Screening?

Colorectal Cancer (CRC) screening of average-risk individuals has been shown to reduce CRC mortality and incidence. Incidence is reduced by detection and removal of cancer precursor lesions (CPLs), resulting in cancer prevention. Mortality reduction is achieved with detection of curable CRC, as well as prevention by removing CPLs before cancer develops. Targets of screening include both curable CRC and CPLs. Non-invasive stool tests are a multi-step screening program which can detect curable cancers and less likely to detect CPLs than invasive screening. The non-invasive programs depend on completion of colonoscopy if the test is positive. Invasive screening with colonoscopy is a one-step test program, with excellent detection of both curable CRCs and CPLs, if performed with high-quality. Current evidence suggests that either program could be effective, despite different targets. Patient adherence and program quality are perhaps the important determinants of program effectiveness.

Barriers and proposed solutions to at-home colorectal cancer screening tests in medically underserved health centers across three US regions to inform a randomized trial.

At-home colorectal cancer (CRC) screening is an effective way to reduce CRC mortality, but screening rates in medically underserved groups are low. To plan the implementation of a pragmatic randomized trial comparing two population-based outreach approaches, we conducted qualitative research on current processes and barriers to at-home CRC screening in 10 community health centers (CHCs) that serve medically underserved groups, four each in Massachusetts and California, and two tribal facilities in South Dakota. We conducted 53 semi-structured interviews with clinical and administrative staff at the participating CHCs. Participants were asked about CRC screening processes, categorized into eight domains: patient identification, outreach, risk assessment, fecal immunochemical test (FIT) workflows, FIT-DNA (i.e., Cologuard) workflows, referral for a follow-up colonoscopy, patient navigation, and educational materials. Transcripts were analyzed using a Rapid Qualitative Analysis approach. A matrix was used to organize and summarize the data into four sub-themes: current process, barriers, facilitators, and solutions to adapt materials for the intervention. Each site's process for stool-based CRC screening varied slightly. Interviewees identified the importance of offering educational materials in English and Spanish, using text messages to remind patients to return kits, adapting materials to address health literacy needs so patients can access instructions in writing, pictures, or video, creating mailed workflows integrated with a tracking system, and offering patient navigation to colonoscopy for patients with an abnormal result. Proposed solutions across the three regions will inform a multilevel intervention in a pragmatic trial to increase CRC screening uptake in CHCs.

Factors Affecting Colorectal Cancer Screening in Primary Care Physician Practices in Ukraine.

This study aims to identify the factors influencing colorectal cancer (CRC) screening practices, along with the barriers and facilitators from the perspective of primary care physicians (PCPs) in Ukraine. Considering health care system challenges, including those posed by the ongoing war, this research seeks to inform improvements in CRC screening and outcomes in Ukraine and other low- and middle-income countries (LMICs). A survey was designed and distributed electronically to Ukrainian PCPs, focusing on CRC screening practices, beliefs, and barriers. The survey incorporated questions adapted from established cancer screening surveys and frameworks. Complete responses were collected from 740 PCPs. Sample statistics were computed, and population-level perceptions and associations with CRC screening practices were estimated by standardizing responses to national PCP demographics. The majority of respondents were women (91%) and specialized in family medicine (84%). Respondents believed in the effectiveness of colonoscopy for reducing CRC mortality (80%), with 75% of PCPs referring patients for this screening modality. Major barriers identified include inadequate training of PCPs in screening and lack of resources. Respondents reported high utilization of fecal occult blood test and colonoscopy for screening when these tests were said to be available in their practices. Self-reported familiarity with CRC screening guidelines and participation in educational workshops were positively associated with screening referrals. The study highlights the role of access to CRC screening tests and awareness of screening guidelines in enhancing CRC screening practices among Ukrainian PCPs. Addressing training and resource barriers, alongside public health interventions targeting patient-related barriers, is essential. These findings offer valuable insights for LMICs facing similar challenges, emphasizing the need for tailored strategies to improve cancer screening in these health care settings.

Introducing Colorectal Cancer Screening in Romania - Preliminary Results from the Regional Pilot Programs (ROCCAS).

Colorectal cancer (CRC) is the third cause of cancer-related death worldwide. Screening programs can reduce CRC mortality rates by up to 60%. In line with the European Union recommendations, Romania started the first four regional pilot screening programs in 2020 (the ROCCAS II projects). This study reports the interim screening performance indicators. People aged 50 to 74 years were invited to the screening program. General practitioners (GPs) evaluated CRC risk based on a survey. High-risk or symptomatic individuals were referred directly to colonoscopy. The average risk participants received a fecal immunochemical test (FIT). Positive cases were invited to colonoscopy. Three regions were screened using the OC-SENSOR® (South-Muntenia, Bucharest-Ilfov, South-East) and one region (South-West) used the FOB GOLD®. The data was collected in the ROCCAS screening electronic registry. The following FIT parameters were evaluated: rates of return, invalidity, positivity, and colonoscopy acceptance rate according to age group, gender, region of provenience, and vulnerability status. We included all cases screened between January 1, 2022 and September 30, 2023. In total, 168,958 people received the FIT test within the projects. The global FIT return rate was 90%. Factors associated with a higher return rate were female gender (90.77% vs 88.83%, p<0.0001), vulnerable status (91.23% vs 88.83%; p<0.00001), and rural residence (91.84% vs 88.42%, p<0.00001). The overall positivity rate was 5.75%. It was higher in males (7.64% vs 4.57% in females, p<0.00001) and progressively increased with the age group. The total invalid FIT rate was 5.87%, significantly lower for OC-SENSOR® (2.24%) than for the FOB GOLD® (13.6%). The overall acceptability rate for colonoscopy was 51.3%. According to our preliminary data, GP's participation in the pilot programs ensured adequate adherence to screening through FIT. The rate for FIT return and positivity were acceptable for both tests, while the invalid rate was much higher in FOB GOLD® compared to the OC-SENSOR®. Moreover, colonoscopy acceptance needs to be improved. Our preliminary analysis revealed the screening performance indicators meet the EU recommendations and fulfill the premises for national-level expansion of the program starting in 2024.

Contributions of early detection and cancer prevention to colorectal cancer mortality reduction by screening colonoscopy: a validated modeling study

Background and aimsScreening colonoscopy, recommended every ten years, reduces mortality from colorectal cancer (CRC) by early detection of prevalent but undiagnosed CRC, as well as by prevention of CRC by removal of precursor lesions. The aim of this study was to assess the relative contribution of both components to total CRC mortality reduction over time. MethodsUsing a validated multistate Markov model, we simulated hypothetical cohorts of 100,000 individuals aged 55-64 with and without use of screening at baseline. Main outcomes included proportions of prevented CRC deaths arising from (asymptomatic) CRC already prevalent at baseline and from newly developed CRC during 15-years of follow-up, and mortality rate ratios of screened versus unscreened groups over time. ResultsEarly detection of prevalent cases accounted for 52%, 30% and 18% of deaths prevented by screening colonoscopy within 5, 10 and 15 years, respectively. Relative reduction of mortality was estimated to be much larger for mortality from incident cancers than for mortality from cancers that were already present and early detected at screening endoscopy and for total CRC mortality (i.e., 88% versus 67% and 79% within 10 years from screening). ConclusionsReduction of CRC mortality mainly arises from early detection of prevalent cancers during the early years after screening colonoscopy, but prevention of incident cases accounts for the majority of prevented deaths in the longer run. Prevention of incident cases leads to sustained strong reduction of colorectal cancer mortality, possibly warranting an extension of screening intervals.

Evaluation of the effectiveness of colorectal cancer screening intervention.

The effectiveness of the Colorectal Cancer (CRC) screening program is assessed based on the reduction in CRC mortality and incidence rates over time. To accurately estimate the long-term impact, it is advisable to monitor additional indicators such as age and stage-specific incidence rates. Our objective is to evaluate the effectiveness of the National CRC Screening Program in Turkey and analyze its influence on disease stage at diagnosis and survival rates. The National CRC Screening Program was considered an intervention and the distribution of local, regional, and distant diseases, and survival estimates were assessed before and after the intervention to evaluate the effectiveness of the intervention. 518 patients were included in the study. At the time of diagnosis, localized, regional, and distant disease in pre-intervention were 31.3%, 42.9%, 25.8%, while post-intervention were 42.8%, 33.3%, 23.9%, respectively (p = 0.020). The relative effectiveness of the intervention in males, females, and 50-70 ages were calculated as 1.2[95% CI 0.95-1.73], 1.5[95% CI 1.04-2.18], and 1.6[95% CI 1.21-2.28] in localized disease, 0.8[95% CI 0.67-1.18], 0.6[95% CI 0.43-0.90], and 0.6[95% CI 0.46-0.81] in regional diseases, 0.8[95% CI 0.57-1.20], 1.1[95% CI 0.66-1.84], and 1.0[95% CI 0.70-1.57] in distant disease, respectively. A noticeable shift in the disease stage at the time of diagnosis was observed; however, this shift varied among gender and age groups. To effectively evaluate the impact of a cancer screening program on reducing the incidence and mortality rates of the disease, it is essential to monitor and analyze these indicators alongside 5-10-year survival estimates and stage changes at the time of diagnosis.

Impact of family history of cancer on colorectal cancer screening: a propensity score-matched analysis from the Health Information National Trends Survey (HINTS)

BackgroundEarly detection of colon cancer leads to better survival outcomes. This can be achieved through colorectal cancer (CRC) screening. People with a family history of cancer (FHC) have increased risk of developing CRC. Increasing screening in this group will reduce CRC mortality. This study evaluated CRC screening in people with FHC.MethodsThe study used data from the Health Information National Trends Survey (HINTS) 5, cycle 3. This is an annual cross-sectional survey with a nationally representative sample of American adults. The objective was to study the association between FHC and performing CRC screening. Propensity score matching was used to create a matched population with variables that constituted beliefs in cancer from the survey. Replication procedure, which is based on repeated sampling and allows for accurate computation of standard errors, was used for calculating statistical tests. Multivariable models were fitted in the matched population to assess the association between FHC and performing CRC screening.ResultsPeople with FHC were 14% (OR = 1.14; 95% CI: 0.81–1.60) more likely to perform CRC screening than those without FHC, even though not statistically significant. Age in years (OR = 1.14; 95% CI: 1.12–5.27) had increased likelihood of performing CRC screening, while other races such as American Indians/Alaskan Natives (except African Americans) compared to Caucasians (OR = 0.49; 95% CI: 0.29–0.84) had significantly decreased likelihood of performing CRC screening.ConclusionFHC was not significantly associated with having a colorectal cancer screening test. Public health advocacy should be directed towards increasing awareness of CRC screening among people with FHC.

Abstract B137: Examining racial disparities in the association between food swamps, liquor store density, and colorectal cancer mortality among Georgia cancer patients

Abstract Introduction: Colorectal cancer (CRC) is the third-most common cancer in the United States (U.S.) and racial/ethnic disparities regarding CRC death continue to persist. Increased healthy food consumption and decreased processed food consumption are key factors in reducing CRC mortality. However, living in geographical areas with no access to healthy food options and more pro-inflammatory foods (i.e. food swamps) decreases healthy food access. The influx of liquor stores, or businesses that advertise and sell unhealthy food products including processed foods and alcohol, may contribute to elevated CRC death. We investigated whether liquor store density modified the association between residing in food swamps with risk of CRC death among a multiethnic sample of cancer patients in Georgia. Methods: We conducted a retrospective cohort analysis utilizing 2012, 2014, 2015, 2017, and 2020 data from the U.S. Department of Agriculture Food Environment Atlas along, U.S. Census County Health Patterns data, and linked them via county FIPS codes with patient data years 2010 – 2020 from the Surveillance, Epidemiology, and End Results (SEER) Program. Food swamp score (FS) was calculated as the ratio of fast-food and convenience stores to grocery stores and farmer’s markets. Liquor store density was calculated as the proportion of beer, wine, and liquor stores to Georgia county populations per 100,000. We categorized FS and liquor store density to low or high; higher scores indicated patients living in counties with poorer healthy food resources. Multilevel Cox proportional hazard models were used to estimate the association between FS, liquor store density and CRC death. Results: Among 56,861 SEER patients in Georgia, majority of CRC death was in high liquor store density counties. NH-Black and Other patients at both levels of FS counties had an increased risk of CRC death (low: adjusted hazard ratio (aHR) = 1.21, 95% CI = 1.16 – 1.26; high: aHR = 1.06, 95% CI = 1.01 – 1.12) when compared to NH-white patients-low-FS counties. In sub-analyses by liquor store density, NH-Black and Other patients-low-FS counties had an increased risk of CRC death among high (aHR = 1.24, 95% CI = 1.19 – 1.31) and low (aHR = 1.12, 95% CI = 1.03 – 1.21) liquor store density counties. Conclusions: NH-Black patients living in the worst food environments, including effect modification by liquor store density, had increased risk of CRC death. We strongly recommend local and state representatives and community stakeholders create and implement sustainable approaches at combating CRC in underserved racial communities by increasing access to healthier food sources (e.g. building more community gardens, fixing barriers to walkability). Citation Format: Malcolm S. Bevel, April Parham, Aashka Sheth, Meng-Han Tsai, Sydney E. Andrzejak, Samantha R. Jones, Justin X. Moore. Examining racial disparities in the association between food swamps, liquor store density, and colorectal cancer mortality among Georgia cancer patients [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B137.

Abstract A138: Impact of racial disparities in follow-up colonoscopy for abnormal stool-screening test results on colorectal cancer incidence and mortality: A simulation modeling analysis

Abstract Introduction: The benefits of colorectal cancer (CRC) screening programs for average-risk adults rely on completion of follow-up colonoscopy (FU-Col) after a positive result from either the stool-based fecal immunochemical test (FIT) or multi-target stool DNA (mt-sDNA) test. Existing data demonstrate significantly lower rates of FU-Col for Black Americans than White Americans. However, the contribution of differential FU-Col rates on disparate CRC outcomes among Black and White Americans has not been rigorously evaluated. Methods: We used the CRC-Adenoma Incidence and Mortality (CRC-AIM) model as our analysis platform, with inputs from published literature that report Black adults are approximately 15% less likely to complete FU-Col compared to White adults. CRC-AIM was validated against United Kingdom Flexible Sigmoidoscopy Screening Trial and three National Cancer Institute’s Cancer Intervention and Surveillance Modeling Network (CISNET) CRC models. We simulated screening with annual FIT and triennial mt-sDNA between ages 45 and 75 versus no screening. We considered two scenarios that assumed perfect adherence to FIT/mt-sDNA screening: 1) FU-Col rates for Black adults are 15% lower than those for White adults; 2) Black adults have the same FU-Col rates as White adults. In a secondary analysis, we considered real-world adherence to FIT (43%) and mt-sDNA (66%) and reran these two scenarios. Lifetime outcomes per 1,000 individuals were reported. Results: Assuming perfect adherence to FIT/mt-sDNA screening and 15% lower FU-Col rates, estimated life-year gains (LYG) from annual FIT and triennial mt-sDNA screening strategies compared to no screening was 227 and 239 per 1,000 individuals, respectively. If Black adults had the same FU-Col rates as White adults, the LYG would increase to 243 and 256 for FIT and mt-sDNA screening, respectively, which corresponds to a 7% improvement in LYG. Furthermore, elimination of racial disparities in FU-Col rates would reduce CRC incidence by 8% and 9% for FIT and mt-sDNA screening, respectively and reduce CRC mortality by 10% for both FIT and mt-sDNA screening. Secondary analysis shows that eliminating disparities in FU-Col would lead to 9-11% improvement in LYGs, 5-9% improvement in CRC incidence, and 7-11% improvement in CRC mortality for Black adults considering the real-world adherence to FIT/mt-sDNA screening. Conclusions: Data from this novel simulation modeling study that accounts for differences in FU-Col rates between Black and White Americans suggest that focused efforts to eliminate this gap would improve the anticipated LYG, CRC incidence, and CRC mortality benefits associated with stool-based CRC screening by over 7%, 8%, and 10%, respectively. Further investigation of this under-appreciated contributor to established racial disparities in CRC control may lead to innovative solutions for improving health equity. Citation Format: Oguz Alagoz, A. Mark Fendrick, Vahab Vahdat, Chris Estes, A. Burak Ozbay, Travelle Ellis, Paul J. Limburg, Durado Brooks. Impact of racial disparities in follow-up colonoscopy for abnormal stool-screening test results on colorectal cancer incidence and mortality: A simulation modeling analysis [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr A138.

Colorectal cancer screening-what does the recent NordICC trial mean for the U.S. population?

The incidence of colorectal cancer (CRC) has declined over time, though it remains a significant cause of morbidity and mortality in the U.S. It has the third highest incidence in incidence among all cancers and is the second leading cause of cancer death in both men and women. Screening reduces the incidence and mortality from CRC. There are several modalities for CRC screening, but the most common ones are a choice between a non-invasive stool-based test, such as fecal immunochemical testing (FIT) or an invasive endoscopic modality, such as colonoscopy. In the U.S. colonoscopy is the predominant CRC screening modality, with observational studies reporting large reductions in CRC incidence and mortality. Recently, a large randomized controlled trial (RCT) on effectiveness of colonoscopy reported smaller than expected reduction in CRC incidence and no reduction in CRC mortality with colonoscopy screening. Explanations of the lower than expected benefit include low uptake of colonoscopy, short follow-up for mortality endpoints and quality indicators (QIs) for some of the endoscopists participating in the screening colonoscopies. The findings of the study need to be taken in context with other literature on effectiveness of colonoscopy, with the overall message of reassuring patients of the benefits of screening, and colonoscopy. Here, we discuss the latest evidence on colonoscopy screening and it in the context of other screening modalities and the landscape.

NordICC Trial Results in Line With Expected Colorectal Cancer Mortality Reduction After Colonoscopy: A Modeling Study

NordICC Trial Results in Line With Expected Colorectal Cancer Mortality Reduction After Colonoscopy: A Modeling Study

Progress of regulatory RNA in small extracellular vesicles in colorectal cancer.

Colorectal cancer (CRC) is the second most common malignant tumor of the gastrointestinal tract with the second highest mortality rate and the third highest incidence rate. Early diagnosis and treatment are important measures to reduce CRC mortality. Small extracellular vesicles (sEVs) have emerged as key mediators that facilitate communication between tumor cells and various other cells, playing a significant role in the growth, invasion, and metastasis of cancer cells. Regulatory RNAs have been identified as potential biomarkers for early diagnosis and prognosis of CRC, serving as crucial factors in promoting CRC cell proliferation, invasion and metastasis, angiogenesis, drug resistance, and immune cell differentiation. This review provides a comprehensive summary of the vital role of sEVs as biomarkers in CRC diagnosis and their potential application in CRC treatment, highlighting their importance as a promising avenue for further research and clinical translation.

Differential impact of test performance characteristics on burden-to-benefit tradeoffs for blood-based colorectal cancer screening: A microsimulation analysis.

To inform the development and evaluation of new blood-based colorectal cancer (CRC) screening tests satisfying minimum United States (US) coverage criteria, we estimated the impact of the different test performance characteristics on long-term testing benefits and burdens. A novel CRC-Microsimulation of Adenoma Progression and Screening (CRC-MAPS) model was developed, validated, then used to assess different screening tests for CRC. We compared multiple, hypothetical blood-based CRC screening tests satisfying minimum coverage criteria of 74% CRC sensitivity and 90% specificity, to measure how changes in a test's CRC sensitivity, specificity, and adenoma sensitivity (sizes 1-5 mm, 6-9 mm, ≥10 mm) affect total number of colonoscopies (COL), CRC incidence reduction (IR), CRC mortality reduction (MR), and burden-to-benefit ratios (incremental COLs per percentage-point increase in IR or MR). A blood test meeting minimum US coverage criteria for performance characteristics resulted in 1576 lifetime COLs per 1000 individuals, 46.7% IR and 59.2% MR compared to no screening. Tests with increased CRC sensitivity of 99% ( + 25%) vs. increased ≥10 mm adenoma sensitivity of 13.6% ( + 3.6%) both yielded the same MR, 62.7%. Test benefits improved the most with increases in all-size adenoma sensitivity, then size-specific adenoma sensitivities, then specificity and CRC sensitivity, while increases in specificity or ≥10 mm adenoma sensitivity resulted in the most favorable burden-to-benefit tradeoffs (ratios <11.5). Burden-to-benefit ratios for blood-based CRC screening tests differ by performance characteristic, with the most favorable tradeoffs resulting from improvements in specificity and ≥10 mm adenoma sensitivity.

Cost-effectiveness of ColoSTAT for primary colorectal cancer screening in the United States.

e15525 Background: Colorectal cancer (CRC) screening is at the cornerstone of strategies for reducing the mortality, healthcare and societal cost burden of CRC, the third most common cancer in the United States (US). ColoSTAT immunoassay is a simple, highly accurate, minimally invasive blood-based screening test for CRC that will be launched in the US market. Using a de novo decision analytic model, we compared the health benefits and cost-effectiveness of CRC screening with ColoSTAT with current screening offered by private insurers assuming a 5-yearly colonoscopy (COL) or biennial fecal immunochemical test (FIT) for the US population. Methods: For the three screening strategies, the expected number of CRC cases detected, and total screening program cost were estimated using a decision-analytic model based on: published CRC incidence in the US, tests performance characteristics, adherence rates to screening (61% for COL; 46% for FIT) and to diagnostic assessment via COL after a positive FIT or ColoSTAT test (80.4%). The gain in quality-adjusted life year (QALY) associated with every CRC case detected through screening, and confirmed by diagnostic assessment, was estimated by linking US-specific estimates of: CRC deaths by age-subgroups, life expectancies at the time of CRC death, quality of life projections for the general population and reduction in CRC mortality associated with screening. Healthcare cost savings associated with every CRC case detected through screening were estimated based on the distribution of CRC across disease stages by diagnosis method (screening versus symptomatically) and stage-specific CRC treatment costs. Results: Biennial screening with ColoSTAT, compared with 5-yearly COL screening offered by private insurers, is estimated to generate cost savings on screening programs of around $40 million per 100,000 people of screening age (PoSA) per one-off screening. When scaled up to the total US population within screening age covered by private insurance (66%), the estimated cost savings with ColoSTAT exceed $30 billion per one-off screening. The reduction in the number of CRC cases detected would generate a modest loss of 58 discounted QALYs per 100,000 people, that could be mitigated if ColoSTAT were to boost screening uptake. In the context of government-sponsored screening programs, replacing FIT with ColoSTAT is estimated to increase the number of CRC cases detected via screening by 9% (to 50 cases per 100,000 PoSA), assuming an unchanged screening uptake of 46%. At the commonly used value of $100,000 per QALY, this would equate to a discounted benefit of $834,820 per 100,000 PoSA per one-off screening. Conclusions: CRC screening with ColoSTAT as an alternative to COL could result in multi-billion-dollar cost savings to US private insurers while still detecting most CRC cases and generate population-health gains if used as an alternative to FIT in government-sponsored screening programs.

The impact of extending CRC screening to the older population: Results from CRC-AIM microsimulation model.

10567 Background: Average-risk screening for colorectal cancer (CRC) is effective and recommended. The U.S. Preventive Services Task Force issued grade A and B recommendations for screening ages 50-75 and 45-49, respectively, however the recommendation for the older population (ages 76-85) is grade C (moderate certainty that the net benefit is small). With emerging blood-based CRC screening, we evaluated the benefits of screening the older population with continued multi-target stool DNA (mt-sDNA) or FIT strategies and/or with a modality shift to blood-based tests after age 75. Methods: Using the validated CRC-AIM microsimulation model, triennial mt-sDNA and annual FIT screening (ages 45-75) followed by four strategies for ages 76-85 (no screening, continued mt-sDNA/FIT, or a modality shift to blood-based screening using either CMS criteria [CMS] or recently reported blood test data from the ECLIPSE study1 [BT; Guardant Health, Inc.] were considered. For CMS criteria and BT, CRC sensitivity were set at 74% and 83%; and adenoma sensitivity was set to 20%, and 13%; and CRC specificity was set to 90% for both tests. Real-world (RWE) adherence for initial screening was set to 80% (CMS, BT), 65.6% (mt-sDNA), and 42.6% (FIT). Adherence for follow-up colonoscopy was set to 72.1% (mt-sDNA, CMS, BT) and 46.0% (FIT). Results: Screening among the population aged 45-85 resulted in 281 life years gained (LYG) with continued mt-sDNA as compared to 193 with continued FIT. Furthermore, mt-sDNA reduced CRC mortality by 70% as compared to 49% by FIT (Table). When screening modality was shifted to CMS (76-85 year olds), mt-sDNA/CMS resulted in 279 LYG as compared to 196 for FIT/CMS. CRC incidence was reduced by 59% (mt-sDNA/CMS) as compared to 38% (FIT/CMS), and mortality declined by 69% (mt-sDNA/CMS) as compared to 51% (FIT/CMS). Reductions in disease burden were lower when modality was switched to BT after age 75 due to reduced test performance. Conclusions: Extending CRC screening to the older population with continued mt-sDNA demonstrated the best health outcomes compared to other modalities. A modality shift after age 75 to blood-based testing resulted in greater LYG as compared to no screening, with performance at CMS criteria yielding better results than BT. Therefore, despite inferior performance, blood-based tests may offer a CRC screening option for older patients who are unable to complete stool testing. [Table: see text]

Polyp detection in the cecum and ascending colon by dye based chromoendoscopy - Is its routine use justified?

colonoscopy is the best method for detecting polyps, with a reduction in colorectal cancer mortality of 29% and reaching 47% for distal tumors. However, it fails to demonstrate a significant reduction in proximal colon cancer mortality, and is the most common segment with interval neoplasm. The present study aimed to evaluate the impact on detection of polyps of a second sequential evaluation of cecum and ascending colon, with or without the use of indigo carmine chromoendoscopy. prospective, non-randomized clinical trial. Patients were divided into two groups. The first (G1) underwent a routine colonoscopy, followed by a second endoscopy assessment of ascending colon and cecum. The second group (G2) underwent a routine colonoscopy, followed by a second assessment of the ascending colon and cecum with indigo carmine chromoendoscopy. In total, 203 patients were analyzed, 101 in the G1 and 102 in the G2. Newer polyps were identified in both groups after the second assessment with a significantly higher number of polyps detected in the patients in the G2 (p=0.0001). The number of patients who had at least one polyp in the two endoscopic assessments was significantly higher in the G2 (53 or 52% vs 27 or 26.7%, p=0.0002). In the second endoscopic assessment, the number of polyps found was also significantly higher in the G2 (50 or 76.9%) compared to the G1 (15 or 23.1%), p<0.0001. the second assessment with dye-based chromoendoscopy increases the detection of polyps in the ascending colon and cecum.