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Aim: Recommendations for surveillance after colonoscopy are based on risk factors for metachronous advanced colorectal neoplasia (AN) and colorectal cancer (CRC). The value of these risk factors remains unclear in populations enriched by individuals with a positive faecal immunochemical test and were investigated in a modern setting. Methods and Results: This population‐based cohort study included all individuals in the Netherlands of ≥55 years old with a first adenoma diagnosis in 2015. A total of 22,471 patients were included. Data were retrieved from the Dutch Nationwide Pathology Databank (Palga). Primary outcomes were metachronous AN and CRC. Patient and polyp characteristics were evaluated by multivariable Cox regression analyses. During follow‐up, 2416 (10.8%) patients were diagnosed with AN, of which 557 (2.5% from the total population) were CRC. Adenomas with high‐grade dysplasia (hazard ratio [HR] 1.60, 95% confidence interval [CI] 1.40–1.83), villous histology (HR 1.91, 95% CI 1.59–2.28), size ≥10 mm (HR 1.12, 95% CI 1.02–1.23), proximal location (HR 1.12, 95% CI 1.02–1.23), two or more adenomas (HR 1.28, 95% CI 1.16–1.41), and serrated polyps ≥10 mm (HR 1.67, 95% CI 1.42–1.97) were independent risk factors for metachronous AN. In contrast, only adenomas with high‐grade dysplasia (HR 2.49, 95% CI 1.92–3.24) were an independent risk factor for metachronous CRC. Conclusions: Risk factors for metachronous AN and CRC were identified for populations with access to a faecal immunochemical test (FIT)‐based screening programme. If only risk factors for metachronous CRC are considered, a reduction in criteria for surveillance seems reasonable. [ABSTRACT FROM AUTHOR]

Background Blood-based biomarker tests can potentially change the landscape of colorectal cancer (CRC) screening. We characterize the conditions under which blood test screening would be as effective and cost-effective as annual fecal immunochemical testing or decennial colonoscopy. Methods We used the 3 Cancer Information and Surveillance Modeling Network–Colon models to compare scenarios of no screening, annual fecal immunochemical testing, decennial colonoscopy, and a blood test meeting Centers for Medicare & Medicaid (CMS) coverage criteria (74% CRC sensitivity and 90% specificity). We varied the sensitivity to detect CRC (74%-92%), advanced adenomas (10%-50%), screening interval (1-3 years), and test cost ($25-$500). Primary outcomes included quality-adjusted life-years (QALY) gained from screening and costs for a US average-risk cohort of individuals aged 45 years. Results Annual fecal immunochemical testing yielded 125-163 QALY gained per 1000 at a cost of $3811-$5384 per person, whereas colonoscopy yielded 132-177 QALY gained at a cost of $5375-$7031 per person. A blood test with 92% CRC sensitivity and 50% advanced adenoma sensitivity yielded 117-162 QALY gained if used every 3 years and 133-173 QALY gained if used every year but would not be cost-effective if priced above $125 per test. If used every 3 years, a $500 blood test only meeting CMS coverage criteria yielded 83-116 QALY gained at a cost of $8559-$9413 per person. Conclusion Blood tests that only meet CMS coverage requirements should not be recommended to patients who would otherwise undergo screening by colonoscopy or fecal immunochemical testing because of lower benefit. Blood tests need higher advanced adenoma sensitivity (above 40%) and lower costs (below $125) to be cost-effective. [ABSTRACT FROM AUTHOR]

In the province-wide colorectal cancer (CRC) screening program in Ontario, Canada, individuals with a family history of CRC are offered colonoscopy screening and those without are offered guaiac fecal occult blood testing (gFOBT, Hemoccult II). We used microsimulation modeling to estimate the cumulative number of CRC deaths prevented and colonoscopies performed between 2008 and 2038 with this family history-based screening program, compared to a regular gFOBT program. In both programs, we assumed screening uptake increased from 30% (participation level in 2008 before the program was launched) to 60%. We assumed that 11% of the population had a family history, defined as having at least one first-degree relative diagnosed with CRC. The programs offered screening between age 50 and 74 years, every two years for gFOBT, and every ten years for colonoscopy. Compared to opportunistic screening (2008 participation level kept constant at 30%), the gFOBT program cumulatively prevented 6,700 more CRC deaths and required 570,000 additional colonoscopies by 2038. The family history-based screening program increased these numbers to 9,300 and 1,100,000, a 40% and 93% increase, respectively. If biennial gFOBT was replaced with biennial fecal immunochemical test (FIT), annual Hemoccult Sensa or five-yearly sigmoidoscopy screening, both the added benefits and colonoscopies required would decrease. A biennial gFOBT screening program that identifies individuals with a family history of CRC and recommends them to undergo colonoscopy screening would prevent 40% (range in sensitivity analyses: 20-51%) additional deaths while requiring 93% (range: 43-116%) additional colonoscopies, compared to a regular gFOBT screening program.

PurposeFamily history of colorectal cancer (CRC) is a known risk factor for CRC and encompasses both genetic and shared environmental risks.MethodsWe conducted a systematic review to estimate the impact of family history on the natural history of CRC and adherence to screening.ResultsWe found high heterogeneity in family-history definitions, the most common definition being one or more first-degree relatives. The prevalence of family history may be lower than the commonly cited 10%, and confirms evidence for increasing levels of risk associated with increasing family-history burden. There is evidence for higher prevalence of adenomas and of multiple adenomas in people with family history of CRC but no evidence for differential adenoma location or adenoma progression by family history. Limited data regarding the natural history of CRC by family history suggest a differential age or stage at cancer diagnosis and mixed evidence with respect to tumor location. Adherence to recommended colonoscopy screening was higher in people with a family history of CRC.ConclusionStratification based on polygenic and/or multifactorial risk assessment may mature to the point of displacing family history-based approaches, but for the foreseeable future, family history may remain a valuable clinical tool for identifying individuals at increased risk for CRC.

INTRODUCTION: Modeling supporting recommendations for colonoscopy and stool-based colorectal cancer (CRC) screening tests assumes 100% sequential participant adherence. The impact of observed adherence on the long-term effectiveness of screening is unknown. We evaluated the effectiveness of a program of screening colonoscopy every 10 years vs annual high-sensitivity guaiac-based fecal occult blood testing (HSgFOBT) using observed sequential adherence data. METHODS: The MIcrosimulation SCreening ANalysis (MISCAN) model used observed sequential screening adherence, HSgFOBT positivity, and diagnostic colonoscopy adherence inHSgFOBT-positive individuals from theNational Colonoscopy Study (single-screening colonoscopy vs ≥4HSgFOBT sequential rounds). We compared CRC incidence and mortality over 15 years with no screening or 10 yearly screening colonoscopy vs annual HSgFOBT with 100% and differential observed adherence from the trial. RESULTS: Without screening, simulated incidence and mortality over 15 years were 20.9 (95% probability interval 15.8-26.9) and 6.9 (5.0-9.2) per 1,000 participants, respectively. In the case of 100% adherence, only screening colonoscopy was predicted to result in lower incidence; however, both tests lowered simulated mortality to a similar level (2.1 [1.6-2.9] for screening colonoscopy and 2.5 [1.8-3.4] for HSgFOBT). Observed adherence for screening colonoscopy (83.6%) was higher than observed sequential HSgFOBT adherence (73.1% first round; 49.1% by round 4), resulting in lower simulated incidence and mortality for screening colonoscopy (14.4 [10.8-18.5] and 2.9 [2.1-3.9], respectively) than HSgFOBT (20.8 [15.8-28.1] and 3.9 [2.9-5.4], respectively), despite a 91% adherence to diagnostic colonoscopy with FOBT positivity. The relative risk of CRC mortality for screening colonoscopy vs HSgFOBT was 0.75 (95% probability interval 0.68-0.80). Findings were similar in sensitivity analyses with alternative assumptions for repeat colonoscopy, test performance, risk, age, and projection horizon. DISCUSSION: Where sequential adherence to stool-based screening is suboptimal and colonoscopy is accessible and acceptable--as observed in the national colonoscopy study, microsimulation, comparative effectiveness, screening recommendations. [ABSTRACT FROM AUTHOR]

A blood-based colorectal cancer (CRC) screening test may increase screening participation. However, blood tests may be less effective than current guideline-endorsed options. The Centers for Medicare & Medicaid Services (CMS) covers blood tests with sensitivity of at least 74% for detection of CRC and specificity of at least 90%. In this study, we investigate whether a blood test that meets these criteria is cost-effective. Three microsimulation models for CRC (MISCAN-Colon, CRC-SPIN, and SimCRC) were used to estimate the effectiveness and cost-effectiveness of triennial blood-based screening (from ages 45 to 75 years) compared to no screening, annual fecal immunochemical testing (FIT), triennial stool DNA testing combined with an FIT assay, and colonoscopy screening every 10 years. The CMS coverage criteria were used as performance characteristics of the hypothetical blood test. We varied screening ages, test performance characteristics, and screening uptake in a sensitivity analysis. Without screening, the models predicted 77–88 CRC cases and 32–36 CRC deaths per 1000 individuals, costing $5.3–$5.8 million. Compared to no screening, blood-based screening was cost-effective, with an additional cost of $25,600–$43,700 per quality-adjusted life-year gained (QALYG). However, compared to FIT, triennial stool DNA testing combined with FIT, and colonoscopy, blood-based screening was not cost-effective, with both a decrease in QALYG and an increase in costs. FIT remained more effective (+5–24 QALYG) and less costly (–$3.2 to –$3.5 million) than blood-based screening even when uptake of blood-based screening was 20 percentage points higher than uptake of FIT. Even with higher screening uptake, triennial blood-based screening, with the CMS-specified minimum performance sensitivity of 74% and specificity of 90%, was not projected to be cost-effective compared with established strategies for colorectal cancer screening. Current test performance characteristics of blood-based colorectal cancer screening tests are insufficient to justify their high costs compared with less expensive and more effective alternatives such as fecal immunochemical testing, triennial stool DNA testing combined with a fecal immunochemical testing assay, and colonoscopy. [ABSTRACT FROM AUTHOR]

Background: Currently all participants of the Dutch colorectal cancer (CRC) screening program with a positive faecal immunochemical test (FIT) are seen at the outpatient clinic to assess their health status, receive information on colonoscopy and CRC risk, and provide informed consent. However, for many patients this information could probably also safely be exchanged in an online setting, in order to reduce the burden for patients, healthcare system, and environment. In this study we will evaluate if a face-to-face pre-colonoscopy consultation can be replaced by a Digital Intake Tool (DIT) in a CRC screening population. Methods: This is a prospective multicentre single-arm, non-randomized study with a non-inferiority design. The DIT will triage a total of 1000 participants and inform them about CRC risk, colonoscopy, sedation, and provide bowel preparation instructions. Participants identified as high-risk (i.e., red-triaged) will be contacted by phone or scheduled for an appointment at the outpatient clinic. The primary outcome measure will be adequate bowel preparation rate, defined as the proportion of participants with a Boston Bowel Preparation (BBPS) score ≥ 6. To compare our primary outcome, we will use colonoscopy data from 1000 FIT positive participants who visited the outpatient clinic for pre-colonoscopy consultation. Secondary outcomes will include participation rate, colonoscopy adherence rate, patient experience in terms of satisfaction and anxiety, knowledge transfer, number of outpatient visits that can be averted by the DIT, and cost-effectiveness of the tool. Ethical approval was obtained from the Medical Ethical Committee of the Erasmus Medical Center (MEC-2021-0098). Discussion: This study aims to assess if a face-to-face pre-colonoscopy consultation can be replaced by an eHealth assessment and education tool in a FIT-based CRC screening program. In case favourable results are established, the intervention evaluated in this study could significantly impact CRC screening programs, benefiting both patients and healthcare systems on a (inter)national scale. Additionally, it would enable more personalized care as the DIT can be easily customized and made feasible in other languages, thereby enhancing healthcare accessibility. Trial registration: Dutch Trial Register: NL9315, date of registration: March 8th, 2021. [ABSTRACT FROM AUTHOR]

This article examines the treatment of stage I colorectal cancers (CRCs) detected within and outside of a screening program in the Netherlands. The study found that screen-detected stage I CRCs were more likely to be treated less invasively, while non-screen-detected stage I CRCs were more likely to undergo surgical oncologic resection. The reasons for this difference in treatment are not fully understood, but factors such as tumor location and differentiation may play a role. Further research is needed to better understand the factors driving these treatment differences. The article does not provide specific details about the researchers mentioned, making it difficult to form any judgments or opinions about their work. [Extracted from the article]

This article discusses the risk of interval post-colonoscopy colorectal cancer (iPCCRC) in individuals who have a negative colonoscopy following a positive fecal immunochemical test (FIT) in a screening program. The study conducted in the Netherlands suggests that there is a risk of iPCCRC in FIT-positive individuals, and the recommended screening interval of 10 years may not be appropriate for this population. The document provides information on the characteristics and risk factors associated with iPCCRC and interval colorectal cancer (FIT IC) after a negative FIT. The study also emphasizes the importance of colonoscopy quality in preventing iPCCRCs and suggests re-evaluating the screening interval after a negative colonoscopy in FIT-based programs. [Extracted from the article]

Aims Advanced serrated polyps (ASPs) have a comparable risk as advanced adenomas (AAs) to progress into colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on AAs and CRC only. We assessed the ASP detection rate, and increase in positive predictive value (PPV) including ASPs in the yield of a FIT-based screening program. Methods We analysed findings of follow-up colonoscopies of FIT-positive screenees in the Dutch CRC screening program from 2014 until 2020. Data was retrieved from the national screening and pathology database. ASP was defined as any serrated polyp ≥10mm, sessile serrated lesion with dysplasia or traditional serrated adenoma. ASP detection rate was defined as the proportion of colonoscopies with ≥1 ASP. PPV was defined as proportion of persons with a CRC or AA. The updated PPV definition included CRC, AA and/or ASPs. Results In total, 322,882 colonoscopies were included in the analyses. Overall detection rate of ASPs was 5.9%. ASPs were more often detected in females than males (6.3% vs 5.6%, p<0.001). ASP detection rates in individuals aged 55-59, 60-64, 65-69 and 70+ were 5.2%; 6.1%; 6.1%; 5.9% (p<0.001), respectively. The PPV for CRC and AA was 41.1% and increased to 43.8% when including ASP. The PPV increase was larger in females than in males (3.2% vs 2.4%). Conclusion A proportion of 5.9% FIT-positive screenees had ASPs, but half of these were detected in combination with CRC or AA. Therefore, including ASPs results in a small increase in the yield of FIT-based screening. [ABSTRACT FROM AUTHOR]

The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT‐based CRC screening program in the Netherlands, using data from individuals who participated in FIT‐screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT‐negative participants (<47 μg Hb/g feces [μg/g]), FIT‐sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f‐Hb). FIT‐sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f‐Hb affects probability of detecting interval CRC, adjusted for sex‐ and age‐differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT‐sensitivity based on the detection method was 84.4% (95%CI 83.8‐85.0) in the first and 73.5% (95% CI 71.8‐75.2) in the second screening round. The proportional incidence method resulted in a FIT‐sensitivity of 76.4% (95%CI 73.3‐79.6) in the first and 79.1% (95%CI 73.7‐85.3) in the second screening round. After one negative FIT, participants with f‐Hb just below the cut‐off (>40‐46.9 μg/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0‐20.4) than had participants with unmeasurable f‐Hb (0‐2.6 μg/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8‐17.6) for participants with f‐Hb just below the cut‐off compared with participants with unmeasurable f‐Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT‐sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk‐stratified CRC screening based on prior f‐Hb. [ABSTRACT FROM AUTHOR]

Background: The adenoma detection rate (ADR) is an essential quality indicator for endoscopists performing colonoscopies for colorectal cancer (CRC) screening as it is associated with postcolonoscopy CRCs (PCCRCs). Currently, data on ADRs of endoscopists performing colonoscopies in fecal immunochemical testing (FIT)-based screening, the most common screening method, are scarce. Also, the association between the ADR and PCCRC has not been demonstrated in this setting.Objective: To evaluate the association between the ADR and PCCRC risk in colonoscopies done after a positive FIT result.Design: Population-based cohort.Setting: Dutch, FIT-based, CRC screening program.Participants: Patients undergoing colonoscopy, done by accredited endoscopists, after a positive FIT result.Measurements: Quality indicator performance and PCCRC incidence for colonoscopies in FIT-positive screenees were assessed. The PCCRCs were classified as interval, a cancer detected before recommended surveillance, or noninterval. The association between ADR and interval PCCRC was evaluated with a multivariable Cox regression model and PCCRC incidence was determined for different ADRs.Results: 362 endoscopists performed 116 360 colonoscopies with a median ADR of 67%. In total, 209 interval PCCRCs were identified. The ADR was associated with interval PCCRC, with an adjusted hazard ratio of 0.95 (95% CI, 0.92 to 0.97) per 1% increase in ADR. For every 1000 patients undergoing colonoscopy, the expected number of interval PCCRC diagnoses after 5 years was approximately 2 for endoscopists with ADRs of 70%, compared with more than 2.5, almost 3.5, and more than 4.5 for endoscopists with ADRs of 65%, 60%, and 55%, respectively.Limitation: The relative short duration of follow-up (median, 52 months) could be considered a limitation.Conclusion: The ADR of endoscopists is inversely associated with the risk for interval PCCRC in FIT-positive colonoscopies. Endoscopists performing colonoscopy in FIT-based screening should aim for markedly higher ADRs compared with primary colonoscopy.Primary Funding Source: None. [ABSTRACT FROM AUTHOR]

Objective: The COVID-19 pandemic forced colorectal cancer (CRC) screening programs to downscale their colonoscopy capacity. In this study, we assessed strategies to deal with temporary restricted colonoscopy capacity in a FIT-based CRC screening program while aiming to retain the maximum possible preventive effect of the screening program. Design: We simulated the Dutch national CRC screening program inviting individuals between ages 55 and 75 for biennial FIT using the MISCAN-Colon model including the 3-month disruption in the first half of 2020 due to the COVID-19 pandemic. For the second half of 2020 and 2021, we simulated three different strategies for the total target population: 1) increasing the FIT cut-off, 2) skipping one screening for specific screening ages, and 3) extending the screening interval. We estimated the impact on required colonoscopy capacity in 2020–2021 and life years (LYs) lost in the long-term. Results: Increasing the FIT cut-off, skipping screening ages and extending the screening interval resulted in a maximum reduction of 25,100 (-17.0%), 16,100(-10.9%) and 19,000 (-12.9%) colonoscopies, respectively. Modelling an increased FIT cut-off, the number of LYs lost ranged between 1,400 and 4,400. Skipping just a single screening age resulted in approximately 2,700 LYs lost and this was doubled in case of skipping two screening ages. Extending the screening interval up to 34 months had the smallest impact on LYs lost (up to 1,100 LYs lost). Conclusion: This modelling study shows that to anticipate on restricted colonoscopy capacity, temporarily extending the screening interval retains the maximum possible preventive effect of the CRC screening program. [ABSTRACT FROM AUTHOR]

Objectives: Colorectal cancer (CRC) screening with a faecal immunochemical test (FIT) has been disrupted in many countries during the COVID-19 pandemic. Performing catch-up of missed screens while maintaining regular screening services requires additional colonoscopy capacity that may not be available. This study aimed to compare strategies that clear the screening backlog using limited colonoscopy resources. Methods: A range of strategies were simulated using four country-specific CRC natural-history models: Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) and MIcrosimulation SCreening ANalysis for CRC (MISCAN-Colon) (both in the Netherlands), Policy1-Bowel (Australia) and OncoSim (Canada). Strategies assumed a 3-month screening disruption with varying recovery period lengths (6, 12, and 24 months) and varying FIT thresholds for diagnostic colonoscopy. Increasing the FIT threshold reduces the number of referrals to diagnostic colonoscopy. Outcomes for each strategy were colonoscopy demand and excess CRC-related deaths due to the disruption. Results: Performing catch-up using the regular FIT threshold in 6, 12 and 24 months could prevent most excess CRC-related deaths, but required 50%, 25% and 12.5% additional colonoscopy demand, respectively. Without exceeding usual colonoscopy demand, up to 60% of excess CRC-related deaths can be prevented by increasing the FIT threshold for 12 or 24 months. Large increases in FIT threshold could lead to additional deaths rather than preventing them. Conclusions: Clearing the screening backlog in 24 months could avert most excess CRC-related deaths due to a 3-month disruption but would require a small increase in colonoscopy demand. Increasing the FIT threshold slightly over 24 months could ease the pressure on colonoscopy resources. [ABSTRACT FROM AUTHOR]

Background: CRC mortality rates are higher for individuals with a lower socioeconomic status (SES). Screening could influence health inequalities. We therefore aimed to investigate SES differences in participation and diagnostic yield of FIT screening. Methods: All invitees in 2014 and 2015 in the Dutch national CRC screening programme were included in the analyses. We used area SES as a measure for SES and divided invitees into quintiles, with Quintile 1 being the highest SES. Logistic regression analysis was used to compare the participation rate, positivity rate, colonoscopy uptake, positive predictive value (PPV) and detection rate across the SES groups. Results: Participation to FIT screening was significantly lower for Quintile 5 (67.0%) compared to the other Quintiles (73.0% to 75.1%; adjusted OR quintile 5 versus quintile 1: 0.73, 95%CI: 0.72–0.74), as well as colonoscopy uptake after a positive FIT (adjusted OR 0.73, 95%CI: 0.69–0.77). The detection rate per FIT participant for advanced neoplasia gradually increased from 3.3% in Quintile 1 to 4.0% in Quintile 5 (adjusted OR 1.20%, 95%CI 1.16–1.24). As a result of lower participation, the yield per invitee was similar for Quintile 5 (2.04%) and Quintile 1 (2.00%), both being lower than Quintiles 2 to 4 (2.20%-2.28%). Conclusions: Screening has the potential to reduce health inequalities in CRC mortality, because of a higher detection in participants with a lower SES. However, in the Dutch screening programme, this is currently offset by the lower participation in this group. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) screening has been demonstrated to reduce CRC incidence and mortality. However, besides such benefits, CRC screening is also associated with potential harmful effects. In an ideal world, screening would only be directed to the small proportion of the population that might potentially benefit. Risk‐based screening can be seen as a first step towards this ideal world, by redistributing screening resources from low‐risk to high‐risk individuals. In theory, this should result in scarce resources being used in individuals who benefit most, while intensity of screening is reduced in individuals who benefit less, hence improving the benefit‐harm ratio among all invitees. Available strategies that have been proposed for risk‐based CRC screening include using information on age, sex, prior screening history, lifestyle and/or genetic information. Implementation of risk‐based screening requires careful consideration of reliable risk prediction models, participation with screening and informed decision‐making. While it is important to recognise the limitations of current approaches, available evidence suggests that it might be feasible to start planning the introduction of tailored strategies within screening programmes. Implementing risk‐based screening based on age, sex and prior screening history alone would already represent a substantial improvement over current uniform screening approaches. We propose that it is time that screening programmes start there and continue striving towards more comprehensive approaches embedding primary prevention as an effective approach to lower risk for everyone. [ABSTRACT FROM AUTHOR]

Background: Fecal immunochemical testing (FIT) is an established method for colorectal cancer (CRC) screening. Measured FIT-concentrations are associated with both present and future risk of CRC, and may be used for personalized screening. However, evaluation of personalized screening is computationally challenging. In this study, a broadly applicable algorithm is presented to efficiently optimize personalized screening policies that prescribe screening intervals and FIT-cutoffs, based on age and FIT-history. Methods: We present a mathematical framework for personalized screening policies and a bi-objective evolutionary algorithm that identifies policies with minimal costs and maximal health benefits. The algorithm is combined with an established microsimulation model (MISCAN-Colon), to accurately estimate the costs and benefits of generated policies, without restrictive Markov assumptions. The performance of the algorithm is demonstrated in three experiments. Results: In Experiment 1, a relatively small benchmark problem, the optimal policies were known. The algorithm approached the maximum feasible benefits with a relative difference of 0.007%. Experiment 2 optimized both intervals and cutoffs, Experiment 3 optimized cutoffs only. Optimal policies in both experiments are unknown. Compared to policies recently evaluated for the USPSTF, personalized screening increased health benefits up to 14 and 4.3%, for Experiments 2 and 3, respectively, without adding costs. Generated policies have several features concordant with current screening recommendations. Discussion: The method presented in this paper is flexible and capable of optimizing personalized screening policies evaluated with computationally-intensive but established simulation models. It can be used to inform screening policies for CRC or other diseases. For CRC, more debate is needed on what features a policy needs to exhibit to make it suitable for implementation in practice. [ABSTRACT FROM AUTHOR]

Background: To evaluate the cost‐effectiveness of prophylactic hysterectomy (PH) in women with Lynch syndrome (LS). Methods: We developed a microsimulation model incorporating the natural history for the development of hyperplasia with and without atypia into endometrial cancer (EC) based on the MISCAN‐framework. We simulated women identified as first‐degree relatives (FDR) with LS of colorectal cancer patients after universal testing for LS. We estimated costs and benefits of offering this cohort PH, accounting for reduced quality of life after PH and for having EC. Three minimum ages (30/35/40) and three maximum ages (70/75/80) were compared to no PH. Results: In the absence of PH, the estimated number of EC cases was 300 per 1,000 women with LS. Total associated costs for treatment of EC were $5.9 million. Offering PH to FDRs aged 40–80 years was considered optimal. This strategy reduced the number of endometrial cancer cases to 5.4 (−98%), resulting in 516 quality‐adjusted life years (QALY) gained and increasing the costs (treatment of endometrial cancer and PH) to $15.0 million (+154%) per 1,000 women. PH from earlier ages was more costly and resulted in fewer QALYs, although this finding was sensitive to disutility for PH. Conclusions: Offering PH to 40‐ to 80‐year‐old women with LS is expected to add 0.5 QALY per person at acceptable costs. Women may decide to have PH at a younger age, depending on their individual disutility for PH and premature menopause. [ABSTRACT FROM AUTHOR]

Objective: The national population-based colorectal cancer screening programme in Hungary was initiated in December 2018. We aimed to evaluate the current programme and investigate the costs and benefits of potential future changes to overcome the low coverage of the target population. Methods: We performed an economic evaluation from a healthcare payer perspective using an established micro-simulation model (Microsimulation Screening Analysis-Colon). We simulated costs and benefits of screening with fecal immunochemical test in the Hungarian population aged 50–100, investigating also the impact of potential future scenarios which were assumed to increase invitation coverage: improvement of the IT platform currently used by GPs or distributing the tests through pharmacies instead of GPs. Results: The model predicted that the current screening programme could lead to 6.2% colorectal cancer mortality reduction between 2018 and 2050 compared to no screening. Even higher reductions, up to 16.6%, were estimated when tests were distributed through pharmacies and higher coverage was assumed. This change in the programme was estimated to require up to 26 million performed fecal immunochemical tests and 1 million colonoscopies for the simulated period. These future scenarios have acceptable cost-benefit ratios of €8000–€8700 per life-years gained depending on the assumed adherence of invited individuals. Conclusions: With its limitations, the current colorectal cancer screening programme in Hungary will have a modest impact on colorectal cancer mortality. Significant improvements in mortality reduction could be made at acceptable costs, if the tests were to be distributed by pharmacies allowing the entire target population to be invited. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "A digital intake tool to avert outpatient visits in a FIT-based colorectal cancer screening population: study protocol of a multicentre, prospective non-randomized trial - the DIT-trial" published in BMC Gastroenterology. The correction addresses an error in the reporting of the sample size calculation. The non-inferiority margin was inaccurately stated as -0.5% instead of the correct value of -8.0%. However, this error does not affect the total number of participants or the study's design and conclusions. The original article has been updated to reflect the correction. [Extracted from the article]

Introduction: In cost-effectiveness analyses, the future costs, disutility and mortality from alternative causes of morbidity are often not completely taken into account. We explored the impact of different assumed values for each of these factors on the cost-effectiveness of screening for colorectal cancer (CRC) and esophageal adenocarcinoma (EAC). Methods: Twenty different CRC screening strategies and two EAC screening strategies were evaluated using microsimulation. Average health-related expenses, disutility and mortality by age for the U.S. general population were estimated using surveys and lifetables. First, we evaluated strategies under default assumptions, with average mortality, and no accounting for health-related costs and disutility. Then, we varied costs, disutility and mortality between 100% and 150% of the estimated population averages, with 125% as the best estimate. Primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained among efficient strategies. Results: The set of efficient strategies was robust to assumptions on future costs, disutility and mortality from other causes of morbidity. However, the incremental cost per QALY gained increased with higher assumed values. For example, for CRC, the ratio for the recommended strategy increased from $15,600 with default assumptions, to $32,600 with average assumption levels, $61,100 with 25% increased levels, and $111,100 with 50% increased levels. Similarly, for EAC, the incremental costs per QALY gained for the recommended EAC screening strategy increased from $106,300 with default assumptions to $198,300 with 50% increased assumptions. In sensitivity analyses without discounting or including only above-average expenses, the impact of assumptions was relatively smaller, but best estimates of the cost per QALY gained remained substantially higher than default estimates. Conclusions: Assumptions on future costs, utility and mortality from other causes of morbidity substantially impact cost-effectiveness outcomes of cancer screening. More empiric evidence and consensus are needed to guide assumptions in future analyses. [ABSTRACT FROM AUTHOR]

The success of fecal occult blood‐based colorectal cancer screening programs is dependent on repeating screening at short intervals (ie, every 1‐2 years). We conducted a literature review to assess measures that have been used to assess longitudinal adherence to fecal‐based screening. Among 46 citations identified and included in this review, six broad classifications of longitudinal adherence were identified: (a) stratified single‐round attendance, (b) all possible adherence permutations, (c) consistent/inconsistent/never attendance, (d) number of times attended, (e) program adherence and (f) proportion of time covered. Advantages and disadvantages of these measures are described, and recommendations on which measures to use based on data availability and scientific question are also given. Stratified single round attendance is particularly useful for describing the yield of screening, while programmatic adherence measures are best suited to evaluating screening efficacy. We recommend that screening programs collect detailed longitudinal, individual‐level data, not only for the screening tests themselves but additionally for diagnostic follow‐up and surveillance exams, to allow for maximum flexibility in reporting adherence patterns using the measure of choice. What's new? Fecal‐based screening for colorectal cancer requires testing at short intervals, usually every one to two years. Consequently, screening program effectiveness is dependent on adherence to repeat screening. Here, the authors describe a literature review aimed at identifying measures to assess adherence to fecal‐based screening over time. In total, six broad categories of measures of longitudinal adherence were identified. Categories varied in amount of individual‐level data required for calculation and in suitability to address specific scientific questions. The authors further provide recommendations for choice of measure to assess longitudinal adherence. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening is cost-effective in many Western countries, and many have successfully implemented CRC screening programs. For countries with a lower CRC incidence, like Saudi Arabia, the value of CRC screening is less evident and requires careful weighing of harms, benefits, and costs. Methods: We used the MISCAN-Colon microsimulation model to simulate a male and female cohort with life expectancy and CRC risk as observed in Saudi Arabia. For both cohorts, we evaluated strategies without screening, with annual or biennial faecal immunochemical testing (FIT), and with 10-yearly or once-only colonoscopy. We also considered different start and end ages of screening. For both cohorts, we estimated lifetime costs and effects of each strategy. We then identified a set of potentially cost-effective strategies using incremental cost-effectiveness ratios (ICERs) defined as the additional cost per additional quality-adjusted life year (QALY). Results: Without CRC screening, an estimated 14 per 1,000 males would develop CRC during their lifetime and 9 would die from CRC. Several strategies proved potentially cost-effective including biennial FIT at ages 55-65 (ICER of $7,400), once-only colonoscopy at age 55 (ICER of $7,700), and 10-yearly colonoscopy at ages 50–65, 45–65, and 45–75 (ICERs of $34,000, 71,000, and 375,000, respectively). For females, risk of CRC was lower and CRC screening was therefore less cost-effective, but efficient strategies were largely similar. Conclusions: Despite low CRC incidence in Saudi Arabia, some FIT or colonoscopy screening strategies may meet reasonable thresholds of cost-effectiveness. The optimal strategy will depend on multiple factors including the willingness to pay per QALY, the colonoscopy capacity, and the accepted budget impact. [ABSTRACT FROM AUTHOR]

Importance: The US Preventive Services Task Force (USPSTF) is updating its 2016 colorectal cancer screening recommendations.Objective: To provide updated model-based estimates of the benefits, burden, and harms of colorectal cancer screening strategies and to identify strategies that may provide an efficient balance of life-years gained (LYG) from screening and colonoscopy burden to inform the USPSTF.Design, Setting, and Participants: Comparative modeling study using 3 microsimulation models of colorectal cancer screening in a hypothetical cohort of 40-year-old US individuals at average risk of colorectal cancer.Exposures: Screening from ages 45, 50, or 55 years to ages 70, 75, 80, or 85 years with fecal immunochemical testing (FIT), multitarget stool DNA testing, flexible sigmoidoscopy alone or with FIT, computed tomography colonography, or colonoscopy. All persons with an abnormal noncolonoscopy screening test result were assumed to undergo follow-up colonoscopy. Screening intervals varied by test. Full adherence with all procedures was assumed.Main Outcome and Measures: Estimated LYG relative to no screening (benefit), lifetime number of colonoscopies (burden), number of complications from screening (harms), and balance of incremental burden and benefit (efficiency ratios). Efficient strategies were those estimated to require fewer additional colonoscopies per additional LYG relative to other strategies.Results: Estimated LYG from screening strategies ranged from 171 to 381 per 1000 40-year-olds. Lifetime colonoscopy burden ranged from 624 to 6817 per 1000 individuals, and screening complications ranged from 5 to 22 per 1000 individuals. Among the 49 strategies that were efficient options with all 3 models, 41 specified screening beginning at age 45. No single age to end screening was predominant among the efficient strategies, although the additional LYG from continuing screening after age 75 were generally small. With the exception of a 5-year interval for computed tomography colonography, no screening interval predominated among the efficient strategies for each modality. Among the strategies highlighted in the 2016 USPSTF recommendation, lowering the age to begin screening from 50 to 45 years was estimated to result in 22 to 27 additional LYG, 161 to 784 additional colonoscopies, and 0.1 to 2 additional complications per 1000 persons (ranges are across screening strategies, based on mean estimates across models). Assuming full adherence, screening outcomes and efficient strategies were similar by sex and race and across 3 scenarios for population risk of colorectal cancer.Conclusions and Relevance: This microsimulation modeling analysis suggests that screening for colorectal cancer with stool tests, endoscopic tests, or computed tomography colonography starting at age 45 years provides an efficient balance of colonoscopy burden and life-years gained. [ABSTRACT FROM AUTHOR]

Summary: Background: Participation in the colorectal cancer screening programme in France has been well below the 45% considered acceptable by European guidelines, potentially attributable to the need to collect the faecal immunochemical test (FIT) at the general practitioner. Aim: To estimate the potential benefits and costs of including the FIT in the invitation letter. Methods: A well‐established microsimulation model was used to simulate the French population 35 years and older in 2018. We estimated quality‐adjusted life‐years (QALY) gained, costs and cost‐effectiveness of the current screening programme, and compared it to a variation of the programme where the FIT was mailed to participants and adherence was assumed to increase to 45%. We also estimated the threshold increase in participation needed to make this intervention cost‐effective. Results: Under the current programme, 53.8 colorectal cancer (CRC) cases and 25.2 CRC deaths per 1000 individuals are expected to occur over a lifetime. If sending out the FIT increases screening participation to 45%, this intervention would result in 6% fewer CRC deaths and 3% fewer CRC cases, resulting in an estimated cost‐effectiveness ratio of €2149 per QALY gained. Sending out the FIT would only need to increase participation by 0.7% point for this intervention to be considered cost‐effective. Conclusion: Including the FIT in the invitation letter is likely a very cost‐effective intervention to increase participation in CRC screening. These results for France are also informative for many other countries around the world where FIT needs to be collected at pharmacies or general practitioners. [ABSTRACT FROM AUTHOR]

Background: There is considerable heterogeneity in individuals' risk of disease and thus the absolute benefits and harms of population-wide screening programmes. Using colorectal cancer (CRC) screening as an exemplar, we explored how people make decisions about screening when presented with information about absolute benefits and harms, and how those preferences vary with baseline risk, between screening tests and between individuals. Method: We conducted two linked studies with members of the public: a think-aloud study exploring decision making in-depth and an online randomised experiment quantifying preferences. In both, participants completed a web-based survey including information about three screening tests (colonoscopy, sigmoidoscopy, and faecal immunochemical testing) and then up to nine scenarios comparing screening to no screening for three levels of baseline risk (1%, 3% and 5% over 15 years) and the three screening tests. Participants reported, after each scenario, whether they would opt for screening (yes/no). Results: Of the 20 participants in the think-aloud study 13 did not consider absolute benefits or harms when making decisions concerning CRC screening. In the online experiment (n = 978), 60% expressed intention to attend at 1% risk of CRC, 70% at 3% and 77% at 5%, with no differences between screening tests. At an individual level, 535 (54.7%) would attend at all three risk levels and 178 (18.2%) at none. The 27% whose intention varied by baseline risk were more likely to be younger, without a family history of CRC, and without a prior history of screening. Conclusions: Most people in our population were not influenced by the range of absolute benefits and harms associated with CRC screening presented. For an appreciable minority, however, magnitude of benefit was important. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) screening with colonoscopy and the fecal immunochemical test (FIT) is underused. Innovative tests could increase screening acceptance. This study determined which of the available alternatives is most promising from a cost-effectiveness perspective.Methods: The previously validated Microsimulation Screening Analysis-Colon model was used to evaluate the cost-effectiveness of screening with capsule endoscopy every 5 or 10 years, computed tomographic colonography every 5 years, the multi-target stool DNA test every 1 or 3 years, and the methylated SEPT9 DNA plasma assay (mSEPT9) every 1 or 2 years. We also compared these strategies with annual FIT screening and colonoscopy screening every 10 years. Quality-adjusted life-years gained (QALYG), number of colonoscopies, and incremental cost-effectiveness ratios were projected. We assumed a willingness-to-pay threshold of $100 000 per QALYG.Results: Among the alternative tests, computed tomographic colonography every 5 years, annual mSEPT9, and annual multi-target stool DNA screening had incremental cost-effectiveness ratios of $1092, $63 253, and $214 974 per QALYG, respectively. Other screening strategies were more costly and less effective than (a combination of) these 3. Under the assumption of perfect adherence, annual mSEPT9 screening resulted in more QALYG, CRC cases averted, and CRC deaths averted than annual FIT screening but led to a high rate of colonoscopy referral (51% after 3 years, 69% after 5 years). The alternative tests were not cost-effective compared with FIT and colonoscopy.Conclusions: This study suggests that for individuals not willing to participate in FIT or colonoscopy screening, mSEPT9 is the test of choice if the high colonoscopy referral rate is acceptable to them. [ABSTRACT FROM AUTHOR]

Microsimulation models are often used to predict long-term outcomes and guide policy decisions regarding cancer screening. The United Kingdom Flexible Sigmoidoscopy Screening (UKFSS) Trial examines a one-time intervention of flexible sigmoidoscopy that was implemented before a colorectal cancer (CRC) screening program was established. Long-term study outcomes, now a full 17 y following randomization, have been published. We use the outcomes from this trial to validate 3 microsimulation models for CRC to long-term study outcomes. We find that 2 of 3 models accurately predict the relative effect of screening (the hazard ratios) on CRC-specific incidence 17 y after screening. We find that all 3 models yield predictions of the relative effect of screening on CRC incidence and mortality (i.e., the hazard ratios) that are reasonably close to the UKFSS results. Two of the 3 models accurately predict the relative reduction in CRC incidence 17 y after screening. One model accurately predicted the absolute incidence and mortality rates in the screened group. The models differ in their estimates related to adenoma detection at screening. Although high-quality screening results help to inform models, trials are expensive, last many years, and can be complicated by ethical issues and technological changes across the duration of the trial. Thus, well-calibrated and validated models are necessary to predict outcomes for which data are not available. The results from this validation demonstrate the utility of models in predicting long-term outcomes and in collaborative modeling to account for uncertainty. [ABSTRACT FROM AUTHOR]

The Dutch colorectal cancer (CRC) screening program started in 2014, inviting the target population biennially to perform a fecal immunochemical test (FIT). We obtained prospectively collected data from the national screening information‐system to present the results of the second round (2016) and evaluate the impact of increasing the FIT cut‐off halfway through the first round from 15 to 47 μg Hb/g feces on outcomes in the second round. Second round screening was done with a 47 μg Hb/g feces FIT cut‐off. Participants were classified based on first round participation status as either FIT (15,47) or FIT (47,47) participants, and previous nonparticipants. In total, 348,891 (75.9%) out of 459,740 invitees participated in the second round. Participation rates were 93.4% among previous participants and 21.0% among previous non‐participants. FIT(47,47) participants had a significantly higher detection rate of AN (15.3 vs. 10.4 per 1,000 participants) compared to FIT(15,47) participants in the second round, while their cumulative detection rate of AN over two rounds was significantly lower (45.6 vs. 52.6 per 1,000 participants). Our results showed that participation in the Dutch CRC screening program was consistently high and that second round detection rates depended on the first round FIT cut‐off. The cumulative detection over two rounds was higher among FIT(15,47) participants. These findings suggest that a substantial part of, but not all the missed findings in the first round due to the increased FIT cut‐off were detected in the subsequent round. What's new? In 2014, the Netherlands implemented colorectal cancer (CRC) screening based on non‐invasive fecal immunochemical testing (FIT), which offers a practical approach for population‐based CRC detection. In the Dutch program's first round, to match local resources, FIT cut‐off was increased, resulting in reduced positivity rates and reduced colonoscopy referrals, at the cost of missing advanced neoplasias. The current study shows that many of these missed advanced neoplasias were detected in subsequent screening, suggesting that increased FIT cut‐off had marginal impact on screening outcome. The findings could benefit other CRC screening programs in establishing effective FIT cut‐offs. [ABSTRACT FROM AUTHOR]

Objective: This study compared the participation in four faecal immunochemical testing-based screening programmes for colorectal cancer in Flanders, France, Basque country and the Netherlands, to identify factors to further optimize faecal immunochemical testing programmes. Method: Background information and data on performance indicators were collected and compared for the four programmes. Results: Invitation method, reminders, funding, faecal immunochemical testing cut-off and follow-up after positive faecal immunochemical testing differed in the four programmes. In France, only an invitation letter is sent by mail, while the sample kit must be collected from the general practitioner. In the other programmes, an invitation letter including the sample kit is sent by mail. Participation rates vary substantially according to the method of invitation, with the highest participation rates in the Netherlands (73.0%) and Basque country (72.4%), followed by Flanders (54.5%) and France (28.6%). Basque country (92.8%) and France (88.4%), the two programmes with most active involvement of general practitioners in referral for colonoscopy, had the highest participation rates for colonoscopy. Conclusions: Large differences in screening participation observed between programmes according to the invitation method used suggest that changes to the design of the programme, such as including the sample kit with the invitation, or active involvement of GPs, might increase participation. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors (CCS) are at increased risk of developing colorectal cancer (CRC) compared to the general population, especially those previously exposed to abdominal or pelvic radiation therapy (APRT). However, the benefits and costs of CRC screening in CCS are unclear. In this study, we evaluated the cost-effectiveness of early-initiated colonoscopy screening in CCS.Methods: We adjusted a previously validated model of CRC screening in the US population (MISCAN-Colon) to reflect CRC and other-cause mortality risk in CCS. We evaluated 91 colonoscopy screening strategies varying in screening interval, age to start, and age to stop screening for all CCS combined and for those treated with or without APRT. Primary outcomes were CRC deaths averted (compared to no screening) and incremental cost-effectiveness ratios (ICERs). A willingness-to-pay threshold of $100 000 per life-years gained (LYG) was used to determine the optimal screening strategy.Results: Compared to no screening, the US Preventive Services Task Force's average risk screening schedule prevented up to 73.2% of CRC deaths in CCS. The optimal strategy of screening every 10 years from age 40 to 60 years averted 79.2% of deaths, with ICER of $67 000/LYG. Among CCS treated with APRT, colonoscopy every 10 years from age 35 to 65 years was optimal (CRC deaths averted: 82.3%; ICER: $92 000/LYG), whereas among those not previously treated with APRT, screening from age 45 to 55 years every 10 years was optimal (CRC deaths averted: 72.7%; ICER: $57 000/LYG).Conclusions: Early initiation of colonoscopy screening for CCS is cost-effective, especially among those treated with APRT. [ABSTRACT FROM AUTHOR]

Background: In 2014, the Centers for Medicare and Medicaid Services (CMS) began covering a multitarget stool DNA (mtSDNA) test for colorectal cancer (CRC) screening of Medicare beneficiaries. In this study, we evaluated whether mtSDNA testing is a cost-effective alternative to other CRC screening strategies reimbursed by CMS, and if not, under what conditions it could be. Methods: We use three independently-developed microsimulation models to simulate a cohort of previously unscreened US 65-year-olds who are screened with triennial mtSDNA testing, or one of six other reimbursed screening strategies. Main outcome measures are discounted life-years gained (LYG) and lifetime costs (CMS perspective), threshold reimbursement rates, and threshold adherence rates. Outcomes are expressed as the median and range across models. Results: Compared to no screening, triennial mtSDNA screening resulted in 82 (range: 79–88) LYG per 1,000 simulated individuals. This was more than for five-yearly sigmoidoscopy (80 (range: 71–89) LYG), but fewer than for every other simulated strategy. At its 2017 reimbursement rate of $512, mtSDNA was the most costly strategy, and even if adherence were 30% higher than with other strategies, it would not be a cost-effective alternative. At a substantially reduced reimbursement rate ($6–18), two models found that triennial mtSDNA testing was an efficient and potentially cost-effective screening option. Conclusions: Compared to no screening, triennial mtSDNA screening reduces CRC incidence and mortality at acceptable costs. However, compared to nearly all other CRC screening strategies reimbursed by CMS it is less effective and considerably more costly, making it an inefficient screening option. [ABSTRACT FROM AUTHOR]

Previous studies on the cost-effectiveness of personalized colorectal cancer (CRC) screening were based on hypothetical performance of CRC risk prediction and did not consider the association with competing causes of death. In this study, we estimated the cost-effectiveness of risk-stratified screening using real-world data for CRC risk and competing causes of death. Risk predictions for CRC and competing causes of death from a large community-based cohort were used to stratify individuals into risk groups. A microsimulation model was used to optimize colonoscopy screening for each risk group by varying the start age (40–60 years), end age (70–85 years), and screening interval (5–15 years). The outcomes included personalized screening ages and intervals and cost-effectiveness compared with uniform colonoscopy screening (ages 45–75, every 10 years). Key assumptions were varied in sensitivity analyses. Risk-stratified screening resulted in substantially different screening recommendations, ranging from a one-time colonoscopy at age 60 for low-risk individuals to a colonoscopy every 5 years from ages 40 to 85 for high-risk individuals. Nevertheless, on a population level, risk-stratified screening would increase net quality-adjusted life years gained (QALYG) by only 0.7% at equal costs to uniform screening or reduce average costs by 1.2% for equal QALYG. The benefit of risk-stratified screening improved when it was assumed to increase participation or costs less per genetic test. Personalized screening for CRC, accounting for competing causes of death risk, could result in highly tailored individual screening programs. However, average improvements across the population in QALYG and cost-effectiveness compared with uniform screening are small. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Individuals with Lynch syndrome (LS) are at increased risk of LS‐related cancers including colorectal cancer (CRC). CRC tumor screening for mismatch repair (MMR) deficiency is recommended in Australia to identify LS, although its cost‐effectiveness has not been assessed. We aim to determine the cost‐effectiveness of screening individuals with CRC for LS at different age‐at‐diagnosis thresholds. Methods: We developed a decision analysis model to estimate yield and costs of LS screening. Age‐specific probabilities of LS diagnosis were based on Australian data. Two CRC tumor screening pathways were assessed (MMR immunohistochemistry followed by MLH1 methylation (MLH1‐Pathway) or BRAF V600E testing (BRAF‐Pathway) if MLH1 expression was lost) for four age‐at‐diagnosis thresholds—screening < 50, screening < 60, screening < 70, and universal screening. Results: Per 1000 CRC cases, screening < 50 identified 5.2 LS cases and cost $A7041 per case detected in the MLH1‐Pathway. Screening < 60 increased detection by 1.5 cases for an incremental cost of $A25 177 per additional case detected. Screening < 70 detected 1.6 additional cases at an incremental cost of $A40 278 per additional case detected. Compared with screening < 70, universal screening detected no additional LS cases but cost $A158 724 extra. The BRAF‐Pathway identified the same number of LS cases for higher costs. Conclusions: The MLH1‐Pathway is more cost‐effective than BRAF‐Pathway for all age‐at‐diagnosis thresholds. MMR immunohistochemistry tumor screening in individuals diagnosed with CRC aged < 70 years resulted in higher LS case detection at a reasonable cost. Further research into the yield of LS screening in CRC patients ≥ 70 years is needed to determine if universal screening is justified. [ABSTRACT FROM AUTHOR]

High participation rates are essential for a screening programme to be beneficial. To reach non-participants in a targeted manner, insight in characteristics of non-participants is needed. We investigated demographic differences between participants and non-participants in the Dutch faecal immunochemical test-based colorectal cancer (CRC) screening programme. In this population-based cohort study, we included all invitees for CRC screening in 2018 and 2019. Participation status, birth year, and sex were extracted from the Dutch national screening information system and linked to demographic characteristics from Statistics Netherlands, including migration background, level of education, socioeconomic category, household composition, and household income. A multivariable logistic regression was used to assess the association between demographic factors and participation. A total of 4,383,861 individuals were invited for CRC screening in 2018 and 2019, of which 3,170,349 (72.3%) participated. Individuals were less likely to participate when they were single and/or living with others (single with other residents versus couple: odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.31–0.38), had a migration background (e.g. Moroccan migrant versus Dutch background: OR 0.43, 95% CI: 0.42–0.44), or had a low income (lowest versus highest quintile: OR 0.45, 95% CI: 0.44–0.45). Although to a lesser extent, non-participation was also significantly associated with being male, being younger, receiving social welfare benefits and having a low level of education. We found that individuals who were single and/or living with others, immigrants from Morocco or individuals with low income were the least likely to participate in the Dutch CRC screening programme. Targeted interventions are needed to minimise inequities in CRC screening. • Characteristics of non-participants in colorectal cancer screening were assessed. • Singles, migrants, those who had low income and males participated less. • Also cohabitation with people other than a partner decreased participation. • First generation migrants show lower participation than second generation migrants. • Targeted interventions are needed to minimise inequities in screening. [ABSTRACT FROM AUTHOR]

Background: Northeastern states of the United States have shown more progress in reducing colorectal cancer (CRC) incidence and mortality rates than Southern states, and this has resulted in considerable disparities. This study quantified how the disparities in CRC rates between Louisiana (a Southern state) and New Jersey (a Northeastern state) would be affected if differences in risk factors, screening, and stage-specific CRC relative survival between the states were eliminated.Methods: This study used the Microsimulation Screening Analysis Colon microsimulation model to estimate age-adjusted CRC incidence and mortality rates in Louisiana from 1995 to 2009 under the assumption that 1) Louisiana had the same smoking and obesity prevalence observed in New Jersey, 2) Louisiana had the same CRC screening uptake observed in New Jersey, 3) Louisiana had the same stage-specific CRC relative survival observed in New Jersey, or 4) all the preceding were true.Results: In 2009, the observed CRC incidence and mortality rates in Louisiana were 141.4 cases and 61.9 deaths per 100,000 individuals, respectively. With the same risk factors and screening observed in New Jersey, the CRC incidence rate in Louisiana was reduced by 3.5% and 15.2%, respectively. New Jersey's risk factors, screening, and survival reduced the CRC mortality rate in Louisiana by 3.0%, 10.8%, and 17.4%, respectively. With all trends combined, the modeled rates per 100,000 individuals in Louisiana became lower than the observed rates in New Jersey for both incidence (116.4 vs 130.0) and mortality (44.7 vs 55.8).Conclusions: The disparities in CRC incidence and mortality rates between Louisiana and New Jersey could be eliminated if Louisiana could attain New Jersey's levels of risk factors, screening, and survival. Priority should be given to enabling Southern states to improve screening and survival rates. [ABSTRACT FROM AUTHOR]

Background: The ColonCancerCheck screening program for colorectal cancer (CRC) in Ontario, Canada, is considering switching from biennial guaiac fecal occult blood test (gFOBT) screening between age 50–74 years to the more sensitive, but also less specific fecal immunochemical test (FIT). The aim of this study is to estimate whether the additional benefits of FIT screening compared to gFOBT outweigh the additional costs and harms. Methods: We used microsimulation modeling to estimate quality adjusted life years (QALYs) gained and costs of gFOBT and FIT, compared to no screening, in a cohort of screening participants. We compared strategies with various age ranges, screening intervals, and cut-off levels for FIT. Cost-efficient strategies were determined for various levels of available colonoscopy capacity. Results: Compared to no screening, biennial gFOBT screening between age 50–74 years provided 20 QALYs at a cost of CAN$200,900 per 1,000 participants, and required 17 colonoscopies per 1,000 participants per year. FIT screening was more effective and less costly. For the same level of colonoscopy requirement, biennial FIT (with a high cut-off level of 200 ng Hb/ml) between age 50–74 years provided 11 extra QALYs gained while saving CAN$333,300 per 1000 participants, compared to gFOBT. Without restrictions in colonoscopy capacity, FIT (with a low cut-off level of 50 ng Hb/ml) every year between age 45–80 years was the most cost-effective strategy providing 27 extra QALYs gained per 1000 participants, while saving CAN$448,300. Interpretation: Compared to gFOBT screening, switching to FIT at a high cut-off level could increase the health benefits of a CRC screening program without considerably increasing colonoscopy demand. [ABSTRACT FROM AUTHOR]