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Objectives: To facilitate informed decision making on participating in colorectal cancer (CRC) screening, we assessed the benefit-harm balance of CRC screening for a wide range of subgroups over different time horizons., Methods: The study combined incidence proportions of benefits and harms of (not) participating in CRC screening estimated by the Adenoma and Serrated pathway to CAncer microsimulation model, a preference eliciting survey, and benefit-harm balance modeling combining all outcomes to determine the net health benefit of CRC screening over 10, 20, and 30 years. Probability of net health benefit was estimated for 210 different subgroups based on age, sex, previous participation in CRC screening, and lifestyle., Results: CRC screening was net beneficial in 183 of 210 subgroups over 30 years (median probability [MP] of 0.79, interquartile range [IQR] of 0.69-0.85) across subgroups. Net health benefit was greater for men (MP 0.82; IQR 0.69-0.89) than women (MP 0.76; IQR 0.67-0.83) and for those without history of participation in previous screenings (MP 0.84; IQR 0.80-0.89) compared with those with (MP 0.69; IQR 0.59-0.75). Net health benefit decreased with increasing age, from MP of 0.84 (IQR 0.80-0.86) at age 55 to 0.61 (IQR 0.56-0.71) at age 75. Shorter time horizons led to lower benefit, with MP of 0.70 (IQR 0.62-0.80) over 20 years and 0.54 (IQR 0.48-0.67) over 10 years., Conclusions: Our benefit-harm analysis provides information about net health benefit of screening participation, based on important characteristics and preferences of individuals, which could assist screening invitees in making informed decisions on screening participation., Competing Interests: Author Disclosures Links to the individual disclosure forms provided by the authors are available here., (Copyright © 2024. Published by Elsevier Inc.)

Longitudinal adherence to colorectal cancer (CRC) screening is reported using different summarizing measures, which hampers international comparison. We provide evidence to guide recommendations on which longitudinal adherence measure to report. Using adherence data over four stool-based CRC screening rounds in three countries, we calculated six summarizing adherence measures; adherence over all rounds, adherence per round, rescreening, full programme adherence (yes/no), regularity (never/inconsistent/consistent screenees) and number of times participated. For each measure, we calculated the accuracy in capturing the observed adherence patterns. Using the ASCCA model, we predicted screening effectiveness when using summarizing measures as model input versus the observed adherence patterns. Adherence over all rounds in the Italian, Spanish and Dutch cohorts was 64.9%, 42.8% and 61.5%, respectively, and the proportion of consistent screenees was 50.9%, 26.3% and 45.7%. Number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as simulating the observed adherence patterns of Italy, Spain and the Netherlands (mortality reductions: 24.4%, 16.9% and 23.5%). Adherence over all rounds and adherence per round were least accurate. Screening effectiveness was overestimated when using adherence over all rounds (mortality reductions: 26.8%, 19.4% and 25.7%) and adherence per round (mortality reductions: 26.8%, 19.5% and 25.9%). To conclude, number of times participated and regularity were most accurate and resulted in similar model-predicted screening effectiveness as using the observed adherence patterns. However they require longitudinal data. To facilitate international comparison of CRC screening programme performance, consensus on an accurate adherence measure to report should be reached., Competing Interests: Declaration of Competing Interest Beatriz Carvalho is inventor on several biomarker patents pending. GA Meijer is co-founder and board member (CSO) of CRCbioscreen BV, he has a research collaboration with CZ Health Insurances (cash matching to ZonMW grant) and he has research collaborations with Exact Sciences, Sysmex, Sentinel Ch. SpA, Personal Genome Diagnostics (PGDX), DELFI and Hartwig Medical Foundation; these companies provide materials, equipment and/or sample/genomic analyses. Evelien Dekker has endoscopic equipment on loan of FujiFilm and Olympus, received a research grant from FujiFilm, and received honorarium for consultancy from FujiFilm, Olympus, GI Supply, CPP-FAP, PAION and Ambu, and speakers' fees from Olympus, GI Supply, Norgine, IPSEN, PAION and FujiFilm., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Colorectal cancer screening programmes worldwide have been disrupted during the COVID-19 pandemic. We aimed to estimate the impact of hypothetical disruptions to organised faecal immunochemical test-based colorectal cancer screening programmes on short-term and long-term colorectal cancer incidence and mortality in three countries using microsimulation modelling., Methods: In this modelling study, we used four country-specific colorectal cancer microsimulation models-Policy1-Bowel (Australia), OncoSim (Canada), and ASCCA and MISCAN-Colon (the Netherlands)-to estimate the potential impact of COVID-19-related disruptions to screening on colorectal cancer incidence and mortality in Australia, Canada, and the Netherlands annually for the period 2020-24 and cumulatively for the period 2020-50. Modelled scenarios varied by duration of disruption (3, 6, and 12 months), decreases in screening participation after the period of disruption (0%, 25%, or 50% reduction), and catch-up screening strategies (within 6 months after the disruption period or all screening delayed by 6 months)., Findings: Without catch-up screening, our analysis predicted that colorectal cancer deaths among individuals aged 50 years and older, a 3-month disruption would result in 414-902 additional new colorectal cancer diagnoses (relative increase 0·1-0·2%) and 324-440 additional deaths (relative increase 0·2-0·3%) in the Netherlands, 1672 additional diagnoses (relative increase 0·3%) and 979 additional deaths (relative increase 0·5%) in Australia, and 1671 additional diagnoses (relative increase 0·2%) and 799 additional deaths (relative increase 0·3%) in Canada between 2020 and 2050, compared with undisrupted screening. A 6-month disruption would result in 803-1803 additional diagnoses (relative increase 0·2-0·4%) and 678-881 additional deaths (relative increase 0·4-0·6%) in the Netherlands, 3552 additional diagnoses (relative increase 0·6%) and 1961 additional deaths (relative increase 1·0%) in Australia, and 2844 additional diagnoses (relative increase 0·3%) and 1319 additional deaths (relative increase 0·4%) in Canada between 2020 and 2050, compared with undisrupted screening. A 12-month disruption would result in 1619-3615 additional diagnoses (relative increase 0·4-0·9%) and 1360-1762 additional deaths (relative increase 0·8-1·2%) in the Netherlands, 7140 additional diagnoses (relative increase 1·2%) and 3968 additional deaths (relative increase 2·0%) in Australia, and 5212 additional diagnoses (relative increase 0·6%) and 2366 additional deaths (relative increase 0·8%) in Canada between 2020 and 2050, compared with undisrupted screening. Providing immediate catch-up screening could minimise the impact of the disruption, restricting the relative increase in colorectal cancer incidence and deaths between 2020 and 2050 to less than 0·1% in all countries. A post-disruption decrease in participation could increase colorectal cancer incidence by 0·2-0·9% and deaths by 0·6-1·6% between 2020 and 2050, compared with undisrupted screening., Interpretation: Although the projected effect of short-term disruption to colorectal cancer screening is modest, such disruption will have a marked impact on colorectal cancer incidence and deaths between 2020 and 2050 attributable to missed screening. Thus, it is crucial that, if disrupted, screening programmes ensure participation rates return to previously observed rates and provide catch-up screening wherever possible, since this could mitigate the impact on colorectal cancer deaths., Funding: Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: Metamodeling can address computational challenges within decision-analytic modeling studies evaluating many strategies. This article illustrates the value of metamodeling for evaluating colorectal cancer screening strategies while accounting for colonoscopy capacity constraints., Methods: In a traditional approach, the best screening strategy was identified from a limited subset of strategies evaluated with the validated Adenoma and Serrated pathway to Colorectal CAncer model. In a metamodeling approach, metamodels were fitted to this limited subset to evaluate all potentially plausible strategies and determine the best overall screening strategy. Approaches were compared based on the best screening strategy in life-years gained compared with no screening. Metamodel runtime and accuracy was assessed., Results: The metamodeling approach evaluated >40 000 strategies in <1 minute with high accuracy after 1 adaptive sampling step (mean absolute error: 0.0002 life-years) using 300 samples in total (generation time: 8 days). Findings indicated that health outcomes could be improved without requiring additional colonoscopy capacity. Obtaining similar insights using the traditional approach could require at least 1000 samples (generation time: 28 days). Suggested benefits from screening at ages <40 years require adequate validation of the underlying Adenoma and Serrated pathway to Colorectal CAncer model before making policy recommendations., Conclusions: Metamodeling allows rapid assessment of a vast set of strategies, which may lead to identification of more favorable strategies compared to a traditional approach. Nevertheless, metamodel validation and identifying extrapolation beyond the support of the original decision-analytic model are critical to the interpretation of results. The screening strategies identified with metamodeling support ongoing discussions on decreasing the starting age of colorectal cancer screening., (Copyright © 2020 ISPOR–The Professional Society for Health Economics and Outcomes Research. Published by Elsevier Inc. All rights reserved.)

Background: Faecal occult blood testing is widely used in colorectal cancer screening. However, there is little empirical long-term evidence on the accumulation of false-positive test results over several screening rounds. We aimed to systematically explore and quantify the cumulative false-positive rate for various scenarios of colorectal cancer screening., Methods: Using a Markov analysis, we estimated the lifetime cumulative number of false-positive test results (cumFP) per 100 000 50-year-old persons. We varied the screening interval and the specificity of a single screening test and the starting age of screening., Results: For a test with a specificity of 98% used from 50 to 74 years, the cumFP at age 74 was 26 260 (1-year interval), 15 102 (2-year interval), and 10 819 (3-year interval), respectively. For a test with a specificity of, respectively, 95 and 92% used at a 2-year interval, the cumFP at age 74 was 2.2 times and 3.0 times higher as compared to a test with a specificity of 98%. The cumFP at age 74 was 18% lower for screening persons aged 54-74 years vs. 50-74 years., Conclusion: Our findings quantitatively illustrate the large variation of the cumFP in colorectal cancer screening between screening strategies, which is relevant to informed decision making and adequate resource planning.

The Australian National Bowel Cancer Screening Program (NBCSP) will fully roll-out 2-yearly screening using the immunochemical Faecal Occult Blood Testing (iFOBT) in people aged 50 to 74 years by 2020. In this study, we aimed to estimate the comparative health benefits, harms, and cost-effectiveness of screening with iFOBT, versus other potential alternative or adjunctive technologies. A comprehensive validated microsimulation model, Policy1-Bowel, was used to simulate a total of 13 screening approaches involving use of iFOBT, colonoscopy, sigmoidoscopy, computed tomographic colonography (CTC), faecal DNA (fDNA) and plasma DNA (pDNA), in people aged 50 to 74 years. All strategies were evaluated in three scenarios: (i) perfect adherence, (ii) high (but imperfect) adherence, and (iii) low adherence. When assuming perfect adherence, the most effective strategies involved using iFOBT (annually, or biennially with/without adjunct sigmoidoscopy either at 50, or at 54, 64 and 74 years for individuals with negative iFOBT), or colonoscopy (10-yearly, or once-off at 50 years combined with biennial iFOBT). Colorectal cancer incidence (mortality) reductions for these strategies were 51-67(74-80)% in comparison with no screening; 2-yearly iFOBT screening (i.e. the NBCSP) would be associated with reductions of 51(74)%. Only 2-yearly iFOBT screening was found to be cost-effective in all scenarios in context of an indicative willingness-to-pay threshold of A$50,000/life-year saved (LYS); this strategy was associated with an incremental cost-effectiveness ratio of A$2,984/LYS-A$5,981/LYS (depending on adherence). The fully rolled-out NBCSP is highly cost-effective, and is also one of the most effective approaches for bowel cancer screening in Australia., (© 2018 UICC.)

Background: The fecal immunochemical test (FIT) for detecting hemoglobin is used widely for noninvasive colorectal cancer (CRC) screening, but its sensitivity leaves room for improvement., Objective: To identify novel protein biomarkers in stool that outperform or complement hemoglobin in detecting CRC and advanced adenomas., Design: Case-control study., Setting: Colonoscopy-controlled referral population from several centers., Participants: 315 stool samples from one series of 12 patients with CRC and 10 persons without colorectal neoplasia (control samples) and a second series of 81 patients with CRC, 40 with advanced adenomas, and 43 with nonadvanced adenomas, as well as 129 persons without colorectal neoplasia (control samples); 72 FIT samples from a third independent series of 14 patients with CRC, 16 with advanced adenomas, and 18 with nonadvanced adenomas, as well as 24 persons without colorectal neoplasia (control samples)., Measurements: Stool samples were analyzed by mass spectrometry. Classification and regression tree (CART) analysis and logistic regression analyses were performed to identify protein combinations that differentiated CRC or advanced adenoma from control samples. Antibody-based assays for 4 selected proteins were done on FIT samples., Results: In total, 834 human proteins were identified, 29 of which were statistically significantly enriched in CRC versus control stool samples in both series. Combinations of 4 proteins reached sensitivities of 80% and 45% for detecting CRC and advanced adenomas, respectively, at 95% specificity, which was higher than that of hemoglobin alone (P < 0.001 and P = 0.003, respectively). Selected proteins could be measured in small sample volumes used in FIT-based screening programs and discriminated between CRC and control samples (P < 0.001)., Limitation: Lack of availability of antibodies prohibited validation of the top protein combinations in FIT samples., Conclusion: Mass spectrometry of stool samples identified novel candidate protein biomarkers for CRC screening. Several protein combinations outperformed hemoglobin in discriminating CRC or advanced adenoma from control samples. Proof of concept that such proteins can be detected with antibody-based assays in small sample volumes indicates the potential of these biomarkers to be applied in population screening., Primary Funding Source: Center for Translational Molecular Medicine, International Translational Cancer Research Dream Team, Stand Up to Cancer (American Association for Cancer Research and the Dutch Cancer Society), Dutch Digestive Foundation, and VU University Medical Center.

Background: Population-based screening to prevent colorectal cancer (CRC) death is effective, but the effectiveness of postpolypectomy surveillance is unclear., Objective: To evaluate the additional benefit in terms of cost-effectiveness of colonoscopy surveillance in a screening setting., Design: Microsimulation using the ASCCA (Adenoma and Serrated pathway to Colorectal CAncer) model., Data Sources: Dutch CRC screening program and published literature., Target Population: Asymptomatic persons aged 55 to 75 years without a prior CRC diagnosis., Time Horizon: Lifetime., Perspective: Health care payer., Intervention: Fecal immunochemical test (FIT) screening with colonoscopy surveillance performed according to the Dutch guideline was simulated. The comparator was no screening or surveillance. FIT screening without colonoscopy surveillance and the effect of extending surveillance intervals were also evaluated., Outcome Measures: CRC burden, colonoscopy demand, life-years, and costs., Results of Base-Case Analysis: FIT screening without surveillance reduced CRC mortality by 50.4% compared with no screening or surveillance. Adding surveillance to FIT screening reduced mortality by an additional 1.7% to 52.1% but increased lifetime colonoscopy demand by 62% (from 335 to 543 colonoscopies per 1000 persons) at an additional cost of €68 000, for an increase of 0.9 life-year. Extending the surveillance intervals to 5 years reduced CRC mortality by 51.8% and increased colonoscopy demand by 42.7% compared with FIT screening without surveillance. In an incremental analysis, incremental cost-effectiveness ratios (ICERs) for screening plus surveillance exceeded the Dutch willingness-to-pay threshold of €36 602 per life-year gained., Results of Sensitivity Analysis: When using a parameter set representing low colorectal lesion prevalence or when colonoscopy costs were halved or colorectal lesion incidence was doubled, screening plus surveillance became cost-effective compared with screening without surveillance., Limitation: Limited data on FIT performance and background CRC risk in the surveillance population., Conclusion: Adding surveillance to FIT screening is not cost-effective based on the Dutch ICER threshold and substantially increases colonoscopy demand. Extending surveillance intervals to 5 years would decrease colonoscopy demand without substantial loss of effectiveness., Primary Funding Source: Alpe d'HuZes, Dutch Cancer Society, and Stand Up To Cancer.

Background: No assessment of the National Bowel Screening Program (NBCSP) in Australia, which considers all downstream benefits, costs, and harms, has been done. We aimed to use a comprehensive natural history model and the most recent information about cancer treatment costs to estimate long-term benefits, costs, and harms of the NBCSP (2 yearly immunochemical faecal occult blood testing screening at age 50-74 years) and evaluate the incremental effect of improved screening participation under different scenarios., Methods: In this modelling study, a microsimulation model, Policy1-Bowel, which simulates the development of colorectal cancer via both the conventional adenoma-carcinoma and serrated pathways was used to simulate the NBCSP in 2006-40, taking into account the gradual rollout of NBCSP in 2006-20. The base-case scenario assumed 40% screening participation (currently observed behaviour) and two alternative scenarios assuming 50% and 60% participation by 2020 were modelled. Aggregate year-by-year screening, diagnosis, treatment and surveillance-related costs, resource utilisation (number of screening tests and colonoscopies), and health outcomes (incident colorectal cancer cases and colorectal cancer deaths) were estimated, as was the cost-effectiveness of the NBCSP., Findings: With current levels of participation (40%), the NBCSP is expected to prevent 92 200 cancer cases and 59 000 deaths over the period 2015-40; an additional 24 300 and 37 300 cases and 16 800 and 24 800 deaths would be prevented if participation was increased to 50% and 60%, respectively. In 2020, an estimated 101 000 programme-related colonoscopies will be done, associated with about 270 adverse events; an additional 32 500 and 49 800 colonoscopies and 88 and 134 adverse events would occur if participation was increased to 50% and 60%, respectively. The overall number needed to screen (NNS) is 647-788 per death prevented, with 52-59 colonoscopies per death prevented. The programme is cost-effective due to the cancer treatment costs averted (cost-effectiveness ratio compared with no screening at current participation, AUS$3014 [95% uncertainty interval 1807-5583] per life-year saved) in the cost-effectiveness analysis. In the budget impact analysis, reduced annual expenditure on colorectal cancer control is expected by 2030, with expenditure reduced by a cumulative AUS$1·7 billion, AUS$2·0 billion, and AUS$2·1 billion (2015 prices) between 2030 and 2040, at participation rates of 40%, 50%, and 60%, respectively., Interpretation: The NBCSP has potential to save 83 800 lives over the period 2015-40 if coverage rates can be increased to 60%. By contrast, the associated harms, although an important consideration, are at a smaller magnitude at the population level. The programme is highly cost-effective and within a decade of full roll-out, there will be reduced annual health systems expenditure on colorectal cancer control due to the impact of screening., Funding: Australia Postgraduate Award PhD Scholarship, Translational Cancer Research Network Top-up scholarship (supported by Cancer Institute NSW) and Cancer Council NSW., (Copyright © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: As in many other European countries, a nationwide screening program for colorectal cancer (CRC) has recently been introduced in the Netherlands. As a side effect, such a screening program will inherently yield an increase in the demand for surveillance after removal of polyps/adenomas or CRC. Although these patients are at increased risk of metachronous colorectal neoplasia, solid evidence on CRC-related mortality reduction as a result of colonoscopy-based surveillance programs is lacking. Furthermore, colonoscopy-based surveillance leads to high patient burden, high logistic demands and high costs. Therefore, new surveillance strategies are needed. The aim of the present study, named Molecular stool testing for Colorectal CAncer Surveillance (MOCCAS), is to determine the performance characteristics of two established non-invasive tests, i.e., the multitarget stool DNA test Cologuard® and the faecal immunochemical test (FIT) in the detection of CRC and advanced adenomas as an alternative for colonoscopy surveillance., Methods: In this observational cross-sectional cohort study, subjects aged 50 to 75 years will be approached to collect (whole-) stool samples for molecular testing and a FIT prior to their scheduled surveillance colonoscopy. The results of the tests will allow calculation of test sensitivities and specificities in the context of surveillance. This will provide the required input for the Dutch ASCCA model (Adenoma and Serrated pathway to Colorectal CAncer) to simulate surveillance strategies differing in frequency and duration. The model will allow predictions of lifetime health effects and costs. Multiple centres in the Netherlands will participate in the study that aims to include 4,000 individuals., Discussion: The outcome of this study will inform on the (cost-) effectiveness of stool based molecular testing as an alternative for colonoscopy in the rapidly expanding surveillance population., Trial Registration: ClinicalTrials.gov ( https://clinicaltrials.gov/ ): NCT02715141 . Retrospectively registered 17 February 2016.

Background: We aimed to predict the long-term colorectal cancer incidence, mortality, and colonoscopy demand of the recently implemented Dutch colorectal cancer screening program., Methods: The Adenoma and Serrated pathway to Colorectal Cancer model was set up to simulate the Dutch screening program consisting of biennial fecal immunochemical testing combined with the new Dutch surveillance guidelines, between 2014 and 2044. The impact of screening and surveillance was evaluated under three sets of natural history assumptions differing in the contribution of the serrated pathway to colorectal cancer incidence. In sensitivity analyses, other assumptions concerning the serrated pathway were varied. Model-predicted outcomes were yearly colorectal cancer incidence, mortality, and colonoscopy demand per year., Results: Assuming an aging population, colorectal cancer incidence under 30 years of screening is predicted to decrease by 35% and 31% for a contribution of 0% and 30% of the serrated pathway to colorectal cancer, respectively. For colorectal cancer mortality, reductions are 47% and 45%. In 2044, 110,000 colonoscopies will be required annually assuming no contribution of the serrated pathway (27 per 1,000 individuals in the screening age range). Including the serrated pathway influences predicted screening effectiveness if serrated lesions are neither detected nor treated at colonoscopy, and/or if colorectal cancers arising from serrated lesions have substantially lower survival rates than those arising from adenomas., Conclusions: The Dutch screening program will markedly decrease colorectal cancer incidence and mortality but considerable colonoscopy resources will be required., Impact: Predictions of long-term screening effectiveness are preferably based on both pathways to colorectal cancer to transparently describe the impact of uncertainties regarding the serrated pathway on long-term predictions., (©2015 American Association for Cancer Research.)

Background: Faecal immunochemical tests (FITs) are commonly used in colorectal cancer (CRC) screening. Diagnostic accuracy of FIT differs between males and females. This so far unexplained difference could result in a dissimilarity in screening outcome between both sexes. The aim of this study is to compare sensitivity and specificity of a FIT between males and females, and study potential explanatory variables., Methods: In this cross-sectional study, data were prospectively collected. 3,022 subjects performed a FIT prior to complete colonoscopy. Sensitivity, specificity, and ROC curves were compared for both sexes. Potential explanatory variables of the relation between sensitivity and sex were explored., Results: At all cut-off values, FIT sensitivity for CRC was higher (range 13-23%) and specificity was lower (range 2-4%) in males compared to females. At 75 ng/ml, sensitivity for CRC was 93% in males compared to 71% in females (p = 0.03), and specificity was 90% in males compared to 93% in females (p = <0.05). For advanced adenomas, males had a slightly higher sensitivity and lower specificity (not significant). At 75 ng/ml, sensitivity for advanced adenomas was 33% in males compared to 29% in females (p = 0.46), and specificity was 93% in males compared to 95% in females (p = 0.22). ROC curves were similar for both sexes, and equal combinations of sensitivity and specificity could be achieved by adjusting the cut-off values. For CRC, the difference in sensitivity could not be explained by age or location of the tumour., Conclusions: FIT has a higher sensitivity and a lower specificity for CRC in males than in females. Equal test characteristics can be achieved by allowing separate cut-off values for both sexes. Location and age do not explain the observed differences in sensitivity.

Background: A single sampled faecal immunochemical test (FIT) has moderate sensitivity for colorectal cancer and advanced adenomas. Repeated FIT sampling could improve test sensitivity. The aim of the present study is to determine whether any of three different strategies of double FIT sampling has a better combination of sensitivity and specificity than single FIT sampling., Methods: Test performance of single FIT sampling in subjects scheduled for colonoscopy was compared to double FIT sampling intra-individually. Test positivity of double FIT sampling was evaluated in three different ways: 1) "one of two FITs+" when at least one out of two measurements exceeded the cut-off value, 2) "two of two FITs+" when both measurements exceeded the cut-off value, 3) "mean of two FITs+" when the geometric mean of two FITs exceeded the cut-off value. Receiver operator curves were calculated and sensitivity of single and the three strategies of double FIT sampling were compared at a fixed level of specificity., Results: In 124 of 1096 subjects, screen relevant neoplasia (SRN) were found (i.e. early stage CRC or advanced adenomas). At any cut-off, "two of two FITs+" resulted in the lowest and "one of two FITs+" in the highest sensitivity for SRN (range 35-44% and 42%-54% respectively). ROC's of double FIT sampling were similar to single FIT sampling. At specificities of 85/90/95%, sensitivity of any double FIT sampling strategy did not differ significantly from single FIT (p-values 0.07-1)., Conclusion: At any cut off, "one of two FITs+" is the most sensitive double FIT sampling strategy. However, at a given specificity level, sensitivity of any double FIT sampling strategy for SRN is comparable to single FIT sampling at a different cut-off value. None of the double FIT strategies has a superior combination of sensitivity and specificity over single FIT., (© 2011 Oort et al; licensee BioMed Central Ltd.)

The faecal immunochemical test (FIT) is widely employed for colorectal cancer screening. However, its sensitivity for advanced precursor lesions remains suboptimal. The multitarget FIT (mtFIT), measuring haemoglobin, calprotectin, and serpin family F member 2, has demonstrated enhanced sensitivity for advanced neoplasia, especially advanced adenomas, at equal specificity to FIT. This study aimed to prospectively validate and investigate the clinical utlitity of mtFIT versus FIT in a setting of population-based colorectal cancer screening. Individuals aged 55–75 years and who were eligible for the Dutch national FIT-based colorectal cancer screening programme were invited to submit both a FIT and mtFIT sample collected from the same bowel movement. Positive FIT (47 μg/g haemoglobin cutoff) or mtFIT (based on decision-tree algorithm) led to a colonoscopy referral. The primary outcome was the relative detection rate of mtFIT versus FIT for all advanced neoplasia. Secondary outcomes were the relative detection rates of colorectal cancer, advanced adenoma, and advanced serrated polyps individually and the long-term effect of mtFIT-based versus FIT-based programmatic screening on colorectal cancer incidence, mortality, and cost, determined with microsimulation modelling. The study has been registered in ClinicalTrials.gov , NCT05314309 , and is complete. Between March 25 and Dec 7, 2022, 35 786 individuals were invited to participate in the study, of whom 15 283 (42·7%) consented, and 13 187 (86·3%) of 15 283 provided both mtFIT and FIT samples with valid results. Of the 13 187 participants, 6637 (50·3%) were male and 6550 (49·7%) were female. mtFIT showed a 9·11% (95% CI 8·62–9·61) positivity rate and 2·27% (95% CI 2·02–2·54) detection rate for advanced neoplasia, compared with a positivity rate of 4·08% (3·75–4·43) and a detection rate of 1·21% (1·03–1·41) for FIT. Detection rates of mtFIT versus FIT were 0·20% (95% CI 0·13–0·29) versus 0·17% (0·11–0·27) for colorectal cancer; 1·64% (1·43–1·87) versus 0·86% (0·72–1·04) for advanced adenoma, and 0·43% (0·33–0·56) versus 0·17% (0·11–0·26) for advanced serrated polyps. Modelling demonstrated that mtFIT-based screening could reduce colorectal cancer incidence by 21% and associated mortality by 18% compared with the current Dutch colorectal cancer screening programme, at feasible costs. Furthermore, at equal positivity rates, mtFIT outperformed FIT in terms of diagnostic yield. At an equally low positivity rate, mtFIT-based screening was predicted to further decrease colorectal cancer incidence by 5% and associated mortality by 4% compared with FIT-based screening. The higher detection rate of mtFIT for advanced adenoma compared with FIT holds the potential to translate into additional and clinically meaningful long-term colorectal cancer incidence and associated mortality reductions in programmatic colorectal cancer screening. Stand Up to Cancer, Dutch Cancer Society, Dutch Digestive Foundation, and Health~Holland. [ABSTRACT FROM AUTHOR]