Publications by authors named "Iris Lansdorp-Vogelaar"

154 Publications

Identifying Key Factors For The Effectiveness Of Pancreatic Cancer Screening: A Model-based Analysis.

Int J Cancer 2021 Feb 28. Epub 2021 Feb 28.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Pancreatic cancer (PC) survival is poor, as detection usually occurs late, when treatment options are limited. Screening of high-risk individuals may enable early detection and a more favorable prognosis. Knowledge gaps prohibit establishing the effectiveness of screening. We developed a microsimulation screening analysis (MISCAN) model to analyze the impact of relevant uncertainties on the effect of PC screening in high-risk individuals. The model simulates two base cases: one in which lesions always progress to PC and one in which indolent and faster progressive lesions co-exist. For each base case, the effect of annual and 5-yearly screening with endoscopic ultrasonography / magnetic resonance imaging was evaluated. The impact of variance in PC risk, screening test characteristics, and surgery-related mortality was evaluated using sensitivity analyses. Screening resulted in a reduction of PC mortality by at least 16% in all simulated scenarios. This reduction depended strongly on the natural disease course (annual screening: -57% for 'Progressive-only' vs -41% for 'Indolent Included'). The number of screen and surveillance tests needed to prevent one cancer death was impacted most by PC risk. A 10% increase in test sensitivity reduced mortality by 1.9% at most. Test specificity is important for the number of surveillance tests. In conclusion, screening reduces PC mortality in all modeled scenarios. The natural disease course and PC risk strongly determines the effectiveness of screening. Test sensitivity seems of lesser influence than specificity. Future research should gain more insight in PC pathobiology to establish the true value of PC screening in high-risk individuals. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/ijc.33540DOI Listing
February 2021

Disability-Adjusted Life Years Averted Versus Quality-Adjusted Life Years Gained: A Model Analysis for Breast Cancer Screening.

Value Health 2021 Mar 25;24(3):353-360. Epub 2021 Jan 25.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Objectives: To quantify the impact of mammography-based screening on the quality of life, disability-adjusted life years (DALYs) averted or quality-adjusted life years (QALYs) gained can be used. We aimed to assess whether the use of DALYs averted or QALYs gained will lead to different cost-effective screening strategies.

Methods: Using the microsimulation model MISCAN, we simulated different breast cancer screening strategies varying in starting age (starting at 45, 47, and 50 years), stopping age (stopping at 69, 72, and 74 years), and frequency (annual [A], biennial [B], combination of both [A + B], and triennial [T]). In total, we defined 24 different breast cancer screening strategies, including no screening as a reference strategy. We calculated incremental cost-effectiveness ratios (ICERs) and compared which strategies were on the efficiency frontiers for DALYs and QALYs.

Results: Breast cancer screening averted between 46.00 and 105.58 DALYs and gained between 28.69 and 64.50 QALYs per 1000 women. For DALYs there were 5 strategies on the efficiency frontier (T50-69, T50-74, T45-74, B45-74, and A45-74). The same strategies plus one (B45-72) were on the efficiency frontier for QALYs.

Conclusions: Using DALYs averted instead of QALYs gained to assess the effects on quality of life from breast cancer screening in the Dutch population yields differences in ICERs, but almost the same strategies were on the efficiency frontiers. Whether the choice in outcome measure leads to a difference in optimal policy depends on the cost-effectiveness threshold.
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http://dx.doi.org/10.1016/j.jval.2020.10.018DOI Listing
March 2021

Development and Validation of Three Regional Microsimulation Models for Predicting Colorectal Cancer Screening Benefits in Europe.

MDM Policy Pract 2021 Jan-Jun;6(1):2381468320984974. Epub 2021 Jan 29.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Validated microsimulation models have been shown to be useful tools in providing support for colorectal cancer (CRC) screening decisions. Aiming to assist European countries in reducing CRC mortality, we developed and validated three regional models for evaluating CRC screening in Europe. Microsimulation Screening Analysis-Colon (MISCAN-Colon) model versions for Italy, Slovenia, and Finland were quantified using data from different national institutions. These models were validated against the best available evidence for the effectiveness of screening from their region (when available): the Screening for COlon REctum (SCORE) trial and the Florentine fecal immunochemical test (FIT) screening study for Italy; the Norwegian Colorectal Cancer Prevention (NORCCAP) trial and the guaiac fecal occult blood test (gFOBT) Finnish population-based study for Finland. When published evidence was not available (Slovenia), the model was validated using cancer registry data. Our three models reproduced age-specific CRC incidence rates and stage distributions in the prescreening period. Moreover, the Italian and Finnish models replicated CRC mortality reductions (reasonably) well against the best available evidence. CRC mortality reductions were predicted slightly larger than those observed (except for the Florentine FIT study), but consistently within the corresponding 95% confidence intervals. Our findings corroborate the MISCAN-Colon reliability in supporting decision making on CRC screening. Furthermore, our study provides the model structure for an additional tool (EU-TOPIA CRC evaluation tool: http://miscan.eu-topia.org) that aims to help policymakers and researchers monitoring or improving CRC screening in Europe.
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http://dx.doi.org/10.1177/2381468320984974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863172PMC
January 2021

The impact of information about different absolute benefits and harms on intention to participate in colorectal cancer screening: A think-aloud study and online randomised experiment.

PLoS One 2021 16;16(2):e0246991. Epub 2021 Feb 16.

The Primary Care Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0246991PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886213PMC
February 2021

Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study.

BMC Gastroenterol 2021 Feb 12;21(1):67. Epub 2021 Feb 12.

Department of Gastroenterology and Hepatology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.

Background: Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions.

Methods: This prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power.

Discussion: TC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy.

Trial Registration: Clinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/show/NCT04180033 .
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http://dx.doi.org/10.1186/s12876-021-01639-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7881638PMC
February 2021

Impact of the COVID-19 pandemic on faecal immunochemical test-based colorectal cancer screening programmes in Australia, Canada, and the Netherlands: a comparative modelling study.

Lancet Gastroenterol Hepatol 2021 Feb 3. Epub 2021 Feb 3.

Department of Public Health, Erasmus University Medical Center, Rotterdam, Netherlands.

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.
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http://dx.doi.org/10.1016/S2468-1253(21)00003-0DOI Listing
February 2021

Modeling costs and benefits of the organized colorectal cancer screening programme and its potential future improvements in Hungary.

J Med Screen 2020 Nov 5:969141320968598. Epub 2020 Nov 5.

Department of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1177/0969141320968598DOI Listing
November 2020

Validation of Colorectal Cancer Models on Long-term Outcomes from a Randomized Controlled Trial.

Med Decis Making 2020 11 20;40(8):1034-1040. Epub 2020 Oct 20.

RAND Corporation, Santa Monica, CA, USA.

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.
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http://dx.doi.org/10.1177/0272989X20961095DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665984PMC
November 2020

Interpretation and adherence to the updated risk-stratified guideline for colonoscopy surveillance after polypectomy - a nationwide survey.

Endosc Int Open 2020 Oct 22;8(10):E1405-E1413. Epub 2020 Sep 22.

Department of Public Health, Erasmus Medical Centre, Rotterdam, The Netherlands.

Low adherence to the Dutch guideline for colonoscopy surveillance after polypectomy led to release of a new guideline in 2013. This new guideline was risk-stratified at a more detailed level than the previous one to achieve more efficient use of colonoscopy resources. This study assessed the feasibility of the risk-stratified guideline by evaluating correct interpretation of and adherence to this guideline. Based on semi-structured interviews with 10 gastroenterologists, we developed an online survey to evaluate gastroenterologists' recommendations for surveillance in 15 example cases of patients with polyps. If recommended intervals differed from the new guideline, respondents were asked to indicate their motives for doing so. Ninety-one of 592 (15.4 %) invited gastroenterologists responded to at least one case, of whom 84 (14.2 %) completed the survey. Gastroenterologists gave a correct recommendation in a median of 10 of 15 cases and adherence per case ranged from 14 % to 95 % (median case 76 %). The two cases that addressed management of serrated polyps were least often answered correctly (14 % and 28 % correct answers). Discrepancies were mainly due to misinterpretation of the guideline with respect to serrated polyps (48 %) or misreading of the questions (30 %). Median adherence to the updated colonoscopy surveillance guideline of 76 % seems reasonable, and is higher than adherence to the previous guideline (range: 22 %-80 %, median 59 %). This shows that detailed (more complex) risk stratification for designation of a surveillance interval is feasible. Adherence could potentially be improved by clarifying correct interpretation of serrated polyps.
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http://dx.doi.org/10.1055/a-1190-3656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7508656PMC
October 2020

Colorectal Cancer Screening in the Novel Coronavirus Disease-2019 Era.

Gastroenterology 2020 Dec 20;159(6):1998-2003. Epub 2020 Sep 20.

Department of Public Health, Erasmus MC, University Medical Center, Rotterdam, the Netherlands.

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http://dx.doi.org/10.1053/j.gastro.2020.09.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7502254PMC
December 2020

Colonoscopy-Related Mortality in a Fecal Immunochemical Test-Based Colorectal Cancer Screening Program.

Clin Gastroenterol Hepatol 2020 Aug 7. Epub 2020 Aug 7.

Department of Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, the Netherlands.

Background & Aims: Many countries have introduced colorectal cancer (CRC) screening programs with fecal immunochemical tests (FITs), and follow-up colonoscopies for individuals with a positive FIT result. In order to make an informed decision to participate, individuals must be informed about the benefits and harms of FIT-based screening and subsequent colonoscopy. Colonoscopy-related fatal complications in FIT-based screening are understudied. We aimed to estimate the colonoscopy-related mortality in a national FIT-based CRC screening program.

Methods: Colonoscopy-related mortality within 30 days after colonoscopy was assessed by analysis of data from national endoscopy complication databases in the Netherlands, determining the excess 30-day rate of death in FIT-positive individuals undergoing colonoscopy vs FIT-negative individuals (based on data from the national screening database), and determining the rate of likely colonoscopy-related deaths based on registered causes of death by the Statistics Netherlands.

Results: Between October 2013 and December 2017, 172,797 participants underwent colonoscopy after a positive result from a FIT in the Dutch national CRC screening program; 13,848 participants received a diagnosis of CRC. The reported fatal complication rate was 0.23 per 10,000 FIT-positive participants (or 1 per 43,199; 95% CI, 0.090 - 0.60) undergoing colonoscopy, whereas this was 0.91 per 10,000 FIT-positive participants (or 1 per 10,961; 95% CI, 0.44 - 1.38) according to the excess death rate. Likely colonoscopy-related causes of death were reported in 0.86 per 10,000 FIT-positive participants (or 1 per 11,236; 95% CI, 0.48 - 1.63) who underwent colonoscopy, of which 50% considered cardiovascular events.

Conclusions: Colonoscopy-related mortality within the Dutch FIT-based CRC screening program was estimated to range from 0.23 to 0.91 per 10,000 FIT-positive participants undergoing colonoscopy. These findings indicate underreporting of fatal complications in registries and a noteworthy incidence of fatal cardiovascular adverse events that requires further investigation. Nevertheless, the harm of FIT-based CRC screening is vastly outweighed by the benefits.
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http://dx.doi.org/10.1016/j.cgh.2020.07.066DOI Listing
August 2020

Comparing the Cost-Effectiveness of Innovative Colorectal Cancer Screening Tests.

J Natl Cancer Inst 2021 Feb;113(2):154-161

Department of Public Health, Erasmus University Medical Center, Rotterdam, the Netherlands.

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.
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http://dx.doi.org/10.1093/jnci/djaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7850547PMC
February 2021

The Impact of the Policy-Practice Gap on Costs and Benefits of Barrett's Esophagus Management.

Am J Gastroenterol 2020 07;115(7):1026-1035

Department of Public Health, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Introduction: Clinical guidelines recommend surveillance of patients with Barrett's esophagus (BE). However, the surveillance intervals in practice are shorter than policy recommendations. We aimed to determine how this policy-practice gap affects the costs and benefits of BE surveillance.

Methods: We used the Netherlands as an exemplary Western country and simulated a cohort of 60-year-old patients with BE using the Microsimulation Screening Analysis model-esophageal adenocarcinoma (EAC) microsimulation model. We evaluated surveillance according to the Dutch guideline and more intensive surveillance of patients without dysplastic BE and low-grade dysplasia. For each strategy, we computed the quality-adjusted life years (QALYs) gained and costs compared with no surveillance. We also performed a budget impact analysis to estimate the increased costs of BE management in the Netherlands for 2017.

Results: Compared with no surveillance, the Dutch guideline incurred an additional &OV0556;5.0 ($5.7) million per 1,000 patients with BE for surveillance and treatment, whereas 57 esophageal adenocarcinoma (EAC) cases (>T1a) were prevented. With intensive and very intensive surveillance strategies for both nondysplastic BE and low-grade dysplasia, the net costs increased by another &OV0556;2.5-5.6 ($2.8-6.5) million while preventing 10-19 more EAC cases and gaining 33-60 more QALYs. On a population level, this amounted to &OV0556;21-47 ($24-54) million (+32%-70%) higher healthcare costs in 2017.

Discussion: The policy-practice gap in BE surveillance intervals results in 50%-114% higher net costs for BE management for only 10%-18% increase in QALYs gained, depending on actual intensity of surveillance. Incentives to eliminate this policy-practice gap should be developed to reduce the burden of BE management on patients and healthcare resources.
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http://dx.doi.org/10.14309/ajg.0000000000000578DOI Listing
July 2020

Calculation of Stop Ages for Colorectal Cancer Screening Based on Comorbidities and Screening History.

Clin Gastroenterol Hepatol 2021 Mar 23;19(3):547-555. Epub 2020 May 23.

Department of Public Health, Erasmus Medical Center, University Medical Center Rotterdam, Rotterdam, The Netherlands.

Background & Aims: Routine screening for colorectal cancer typically is recommended until age 74 years. Although it has been proposed that a screening stop age could be determined based on sex and comorbidity, less is known about the impact of screening history. We investigated the effects of screening history on the selection of an optimal age to stop screening.

Methods: We used the Microsimulation Screening Analysis-Colon model to estimate the harms and benefits of screening with biennial fecal immunochemical tests by sex, comorbidity status, and screening history. The optimal screening stop age was determined based on the incremental number needed for 1 additional life-year per 1000 screened individuals compared with the threshold provided by stopping screening at 76 years in the average-health population with a perfect screening history (attended all required screening, diagnostic, and follow-up tests) to biennial fecal immunochemical testing from age 50 years.

Results: For persons age 76 years, 157 women and 108 men with a perfect screening history would need to be screened to gain 1 life-year per 1000 screened individuals. Previously unscreened women with no comorbid conditions and no history of screening could undergo an initial screening through 90 years, whereas unscreened men could undergo initial screening through 88 years, before this balance is reached. As screening adherence improved or as comorbidities increased, the optimal age to stop screening decreased to a point that, regardless of sex, individuals with severe comorbidities and a perfect screening history should stop screening at age 66 years or younger.

Conclusions: Based on the harm-benefit balance, the optimal stop age for colorectal cancer screening ranges from 66 years for unhealthy individuals with a perfect screening history to 90 years for healthy individuals without prior screening. These findings can be used to assist patients and clinicians in making decisions about screening participation.
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http://dx.doi.org/10.1016/j.cgh.2020.05.038DOI Listing
March 2021

Prevalence and Clinical Features of Sessile Serrated Polyps: A Systematic Review.

Gastroenterology 2020 Jul 18;159(1):105-118.e25. Epub 2020 Mar 18.

Department of Medicine, Stanford University, Stanford, California.

Background & Aims: Sessile serrated polyps (SSPs) could account for a substantial proportion of colorectal cancers. We aimed to increase clarity on SSP prevalence and clinical features.

Methods: We performed a systematic review of MEDLINE, Web of Science, Embase, and Cochrane databases for original studies published in English since 2000. We included studies of different populations (United States general or similar), interventions (colonoscopy, autopsy), comparisons (world regions, alternative polyp definitions, adenoma), outcomes (prevalence, clinical features), and study designs (cross-sectional). Random-effects regression was used for meta-analysis where possible.

Results: We identified 74 relevant colonoscopy studies. SSP prevalence varied by world region, from 2.6% in Asia (95% confidence interval [CI], 0-5.9) to 10.5% in Australia (95% CI, 2.8-18.2). Prevalence values did not differ significantly between the United States and Europe (P = .51); the pooled prevalence was 4.6% (95% CI, 3.4-5.8), and SSPs accounted for 9.4% of polyps with malignant potential (95% CI, 6.6-12.3). The mean prevalence was higher when assessed through high-performance examinations (9.1%; 95% CI, 4.0-14.2; P = .04) and with an alternative definition of clinically relevant serrated polyps (12.3%; 95% CI, 9.3-15.4; P < .001). Increases in prevalence with age were not statistically significant, and prevalence did not differ significantly by sex. Compared with adenomas, a higher proportion of SSPs were solitary (69.0%; 95% CI, 45.9-92.1; P = .08), with diameters of 10 mm or more (19.3%; 95% CI, 12.4-26.2; P = .13) and were proximal (71.5%; 95% CI, 63.5-79.5; P = .008). The mean ages for detection of SSP without dysplasia, with any or low-grade dysplasia, and with high-grade dysplasia were 60.8 years, 65.6 years, and 70.2 years, respectively. The range for proportions of SSPs with dysplasia was 3.7%-42.9% across studies, possibly reflecting different study populations.

Conclusions: In a systematic review, we found that SSPs are relatively uncommon compared with adenoma. More research is needed on appropriate diagnostic criteria, variations in detection, and long-term risk.
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http://dx.doi.org/10.1053/j.gastro.2020.03.025DOI Listing
July 2020

Intensity of Surveillance for Patients With Colorectal Adenomas.

Ann Intern Med 2020 03;172(6):442

Stanford University, Stanford, California (U.L.).

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http://dx.doi.org/10.7326/L19-0829DOI Listing
March 2020

Cost-Effectiveness of Risk-Stratified Colorectal Cancer Screening Based on Polygenic Risk: Current Status and Future Potential.

JNCI Cancer Spectr 2020 Feb 14;4(1):pkz086. Epub 2019 Oct 14.

See the Notes section for the full list of authors' affiliations.

Background: Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be.

Methods: The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years).

Results: With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation.

Conclusions: Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening.
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http://dx.doi.org/10.1093/jncics/pkz086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6988584PMC
February 2020

Diagnostic Accuracy of Stool Tests for Colorectal Cancer Surveillance in Hodgkin Lymphoma Survivors.

J Clin Med 2020 Jan 10;9(1). Epub 2020 Jan 10.

Department of Gastroenterology, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.

Background: Hodgkin lymphoma (HL) survivors have an increased colorectal cancer (CRC) risk. Diagnostic accuracy of quantitative fecal immunochemical testing (FIT, OC Sensor) and/or a multi-target stool DNA test (mt-sDNA, Cologuard) for advanced neoplasia (AN) was evaluated.

Methods: 101 HL survivors underwent a surveillance colonoscopy and were asked to perform two stool tests (FIT and mt-sDNA). Advanced adenoma (AA), advanced serrated lesion (ASL), and AN (AA, ASL, CRC) were evaluated. Sensitivity, specificity, and area under the curve (AUC) for AN were calculated for different FIT cut-offs and mt-sDNA with colonoscopy as reference.

Results: FIT and mt-sDNA were analyzed in 73 (72%) and 82 (81%) participants, respectively. AN was detected in 19 (26%) and 22 (27%), respectively. AN sensitivities for FIT cut-off of 10 ug Hb/g feces (FIT10) and mt-sDNA were 37% (95% confidence interval (CI): 16-62) and 68% (95% CI: 45-86), with corresponding specificities of 91% (95% CI: 80-97) and 70% (95% CI: 57-86), respectively. AUC for FIT was 0.68 (95% CI: 0.54-0.82) and for mt-sDNA 0.76 (95% CI: 0.63-0.89).

Conclusions: In HL survivors, mt-sDNA showed highest sensitivity but with relatively low specificity for AN. Cost-effectiveness analyses is necessary to determine the optimal surveillance strategy.
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http://dx.doi.org/10.3390/jcm9010190DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7019558PMC
January 2020

Impact of colorectal cancer screening on cancer-specific mortality in Europe: A systematic review.

Eur J Cancer 2020 03 10;127:224-235. Epub 2020 Jan 10.

Erasmus MC, University Medical Center Rotterdam, Department of Public Health, Rotterdam, the Netherlands.

Background: Populations differ with respect to their cancer risk and screening preferences, which may influence the performance of colorectal cancer (CRC) screening programs. This review aims to systematically compare the mortality effect of CRC screening across European regions.

Methods: Six databases including Embase, Medline, Web of Science, PubMed publisher, Google Scholar and Cochrane Library were searched for relevant studies published before March 2018. Bibliographic searches were conducted to select studies assessing the effect of various screening tests (guaiac fecal occult blood test [gFOBT]; flexible sigmoidoscopy [FS]; fecal immunochemical test [FIT] and colonoscopy) on CRC mortality in Europe (PROSPERO protocol: CRD42016042433). Abstract reviewing, data extraction and risk of bias assessment were conducted independently by two reviewers.

Results: A total of 18 studies were included; of which, 11 were related to gFOBT, 4 to FS, 2 to FIT and 1 to colonoscopy; 8 were randomised clinical trials, and 10, observational studies, and an approximately equal number of studies represented Northern, Western and Southern European regions. Among individuals invited to screening, CRC mortality reductions varied from 8% to 16% for gFOBT and from 21% to 30% for FS. When studies with a high risk of bias were considered, ranges were more extensive. The estimated effectiveness of gFOBT and FS screening appeared similar across different European regions.

Conclusions: CRC mortality impact of inviting individuals with similar adopted screening strategies (gFOBT or FS) may be consistent across several European settings.
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http://dx.doi.org/10.1016/j.ejca.2019.12.014DOI Listing
March 2020

Cumulative Burden of Colorectal Cancer-Associated Genetic Variants Is More Strongly Associated With Early-Onset vs Late-Onset Cancer.

Authors:
Alexi N Archambault Yu-Ru Su Jihyoun Jeon Minta Thomas Yi Lin David V Conti Aung Ko Win Lori C Sakoda Iris Lansdorp-Vogelaar Elisabeth F P Peterse Ann G Zauber David Duggan Andreana N Holowatyj Jeroen R Huyghe Hermann Brenner Michelle Cotterchio Stéphane Bézieau Stephanie L Schmit Christopher K Edlund Melissa C Southey Robert J MacInnis Peter T Campbell Jenny Chang-Claude Martha L Slattery Andrew T Chan Amit D Joshi Mingyang Song Yin Cao Michael O Woods Emily White Stephanie J Weinstein Cornelia M Ulrich Michael Hoffmeister Stephanie A Bien Tabitha A Harrison Jochen Hampe Christopher I Li Clemens Schafmayer Kenneth Offit Paul D Pharoah Victor Moreno Annika Lindblom Alicja Wolk Anna H Wu Li Li Marc J Gunter Andrea Gsur Temitope O Keku Rachel Pearlman D Timothy Bishop Sergi Castellví-Bel Leticia Moreira Pavel Vodicka Ellen Kampman Graham G Giles Demetrius Albanes John A Baron Sonja I Berndt Stefanie Brezina Stephan Buch Daniel D Buchanan Antonia Trichopoulou Gianluca Severi María-Dolores Chirlaque Maria-José Sánchez Domenico Palli Tilman Kühn Neil Murphy Amanda J Cross Andrea N Burnett-Hartman Stephen J Chanock Albert de la Chapelle Douglas F Easton Faye Elliott Dallas R English Edith J M Feskens Liesel M FitzGerald Phyllis J Goodman John L Hopper Thomas J Hudson David J Hunter Eric J Jacobs Corinne E Joshu Sébastien Küry Sanford D Markowitz Roger L Milne Elizabeth A Platz Gad Rennert Hedy S Rennert Fredrick R Schumacher Robert S Sandler Daniela Seminara Catherine M Tangen Stephen N Thibodeau Amanda E Toland Franzel J B van Duijnhoven Kala Visvanathan Ludmila Vodickova John D Potter Satu Männistö Korbinian Weigl Jane Figueiredo Vicente Martín Susanna C Larsson Patrick S Parfrey Wen-Yi Huang Heinz-Josef Lenz Jose E Castelao Manuela Gago-Dominguez Victor Muñoz-Garzón Christoph Mancao Christopher A Haiman Lynne R Wilkens Erin Siegel Elizabeth Barry Ban Younghusband Bethany Van Guelpen Sophia Harlid Anne Zeleniuch-Jacquotte Peter S Liang Mengmeng Du Graham Casey Noralane M Lindor Loic Le Marchand Steven J Gallinger Mark A Jenkins Polly A Newcomb Stephen B Gruber Robert E Schoen Heather Hampel Douglas A Corley Li Hsu Ulrike Peters Richard B Hayes

Gastroenterology 2020 04 19;158(5):1274-1286.e12. Epub 2019 Dec 19.

Division of Epidemiology, Department of Population Health, New York University School of Medicine, New York, New York. Electronic address:

Background & Aims: Early-onset colorectal cancer (CRC, in persons younger than 50 years old) is increasing in incidence; yet, in the absence of a family history of CRC, this population lacks harmonized recommendations for prevention. We aimed to determine whether a polygenic risk score (PRS) developed from 95 CRC-associated common genetic risk variants was associated with risk for early-onset CRC.

Methods: We studied risk for CRC associated with a weighted PRS in 12,197 participants younger than 50 years old vs 95,865 participants 50 years or older. PRS was calculated based on single nucleotide polymorphisms associated with CRC in a large-scale genome-wide association study as of January 2019. Participants were pooled from 3 large consortia that provided clinical and genotyping data: the Colon Cancer Family Registry, the Colorectal Transdisciplinary Study, and the Genetics and Epidemiology of Colorectal Cancer Consortium and were all of genetically defined European descent. Findings were replicated in an independent cohort of 72,573 participants.

Results: Overall associations with CRC per standard deviation of PRS were significant for early-onset cancer, and were stronger compared with late-onset cancer (P for interaction = .01); when we compared the highest PRS quartile with the lowest, risk increased 3.7-fold for early-onset CRC (95% CI 3.28-4.24) vs 2.9-fold for late-onset CRC (95% CI 2.80-3.04). This association was strongest for participants without a first-degree family history of CRC (P for interaction = 5.61 × 10). When we compared the highest with the lowest quartiles in this group, risk increased 4.3-fold for early-onset CRC (95% CI 3.61-5.01) vs 2.9-fold for late-onset CRC (95% CI 2.70-3.00). Sensitivity analyses were consistent with these findings.

Conclusions: In an analysis of associations with CRC per standard deviation of PRS, we found the cumulative burden of CRC-associated common genetic variants to associate with early-onset cancer, and to be more strongly associated with early-onset than late-onset cancer, particularly in the absence of CRC family history. Analyses of PRS, along with environmental and lifestyle risk factors, might identify younger individuals who would benefit from preventive measures.
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http://dx.doi.org/10.1053/j.gastro.2019.12.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103489PMC
April 2020

The second round of the Dutch colorectal cancer screening program: Impact of an increased fecal immunochemical test cut-off level on yield of screening.

Int J Cancer 2020 Aug 9;147(4):1098-1106. Epub 2020 Jan 9.

Department of Public Health, Erasmus University Medical Center, Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.1002/ijc.32839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383838PMC
August 2020

Optimizing Management of Patients With Barrett's Esophagus and Low-Grade or No Dysplasia Based on Comparative Modeling.

Clin Gastroenterol Hepatol 2020 Aug 6;18(9):1961-1969. Epub 2019 Dec 6.

Division of Gastroenterology, Department of Medicine, University of Washington, Seattle, Washington.

Background & Aims: Endoscopic treatment is recommended for patients with Barrett's esophagus (BE) with high-grade dysplasia, yet clinical management recommendations are inconsistent for patients with BE without dysplasia (NDBE) or with low-grade dysplasia (LGD). We used a comparative modeling analysis to identify optimal management strategies for these patients.

Methods: We used 3 independent population-based models to simulate cohorts of 60-year-old individuals with BE in the United States. We followed up each cohort until death without surveillance and treatment (natural disease progression), compared with 78 different strategies of management for patients with NDBE or LGD. We determined the optimal strategy using cost-effectiveness analyses, at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY).

Results: In the 3 models, the average cumulative incidence of esophageal adenocarcinoma was 111 cases, with costs totaling $5.7 million per 1000 men with BE. Surveillance and treatment of men with BE prevented 23% to 75% of cases of esophageal adenocarcinoma, but increased costs to $6.2 to $17.3 million per 1000 men with BE. The optimal strategy was surveillance every 3 years for men with NDBE and treatment of LGD after confirmation by repeat endoscopy (incremental cost-effectiveness ratio, $53,044/QALY). The average results for women were consistent with the results for men for LGD management, but the optimal surveillance interval for women with NDBE was 5 years (incremental cost-effectiveness ratio, $36,045/QALY).

Conclusions: Based on analyses from 3 population-based models, the optimal management strategy for patient with BE and LGD is endoscopic eradication, but only after LGD is confirmed by a repeat endoscopy. The optimal strategy for patients with NDBE is endoscopic surveillance, using a 3-year interval for men and a 5-year interval for women.
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http://dx.doi.org/10.1016/j.cgh.2019.11.058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447845PMC
August 2020

Using Patient Preferences to Determine Noninferiority Margins in Trials.

JAMA 2019 12;322(21):2137-2138

Department of Public Health, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

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http://dx.doi.org/10.1001/jama.2019.16336DOI Listing
December 2019

Cost-Effectiveness of Personalized Screening for Colorectal Cancer Based on Polygenic Risk and Family History.

Cancer Epidemiol Biomarkers Prev 2020 01 20;29(1):10-21. Epub 2019 Nov 20.

Erasmus MC, University Medical Center Rotterdam, Department of Public Health, Rotterdam, the Netherlands.

Background: There is growing evidence for personalizing colorectal cancer screening based on risk factors. We compared the cost-effectiveness of personalized colorectal cancer screening based on polygenic risk and family history to uniform screening.

Methods: Using the MISCAN-Colon model, we simulated a cohort of 100 million 40-year-olds, offering them uniform or personalized screening. Individuals were categorized based on polygenic risk and family history of colorectal cancer. We varied screening strategies by start age, interval and test and estimated costs, and quality-adjusted life years (QALY). In our analysis, we (i) assessed the cost-effectiveness of uniform screening; (ii) developed personalized screening scenarios based on optimal screening strategies by risk group; and (iii) compared the cost-effectiveness of both.

Results: At a willingness-to-pay threshold of $50,000/QALY, the optimal uniform screening scenario was annual fecal immunochemical testing (FIT) from ages 50 to 74 years, whereas for personalized screening the optimal screening scenario consisted of annual and biennial FIT screening except for those at highest risk who were offered 5-yearly colonoscopy from age 50 years. Although these scenarios gained the same number of QALYs (17,887), personalized screening was not cost-effective, costing an additional $428,953 due to costs associated with determining risk (assumed to be $240 per person). Personalized screening was cost-effective when these costs were less than ∼$48.

Conclusions: Uniform colorectal cancer screening currently appears more cost-effective than personalized screening based on polygenic risk and family history. However, cost-effectiveness is highly dependent on the cost of determining risk.

Impact: Personalized screening could become increasingly viable as costs for determining risk decrease.
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http://dx.doi.org/10.1158/1055-9965.EPI-18-1123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7159991PMC
January 2020

Participation in faecal immunochemical testing-based colorectal cancer screening programmes in the northwest of Europe.

J Med Screen 2020 06 23;27(2):68-76. Epub 2019 Oct 23.

Gastroenterology, Netherlands Cancer Institute - Antoni van Leeuwenhoek, Amsterdam, The Netherlands.

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.
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http://dx.doi.org/10.1177/0969141319879712DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7222964PMC
June 2020

Cost-effectiveness of Active Identification and Subsequent Colonoscopy Surveillance of Lynch Syndrome Cases.

Clin Gastroenterol Hepatol 2020 Nov 17;18(12):2760-2767.e12. Epub 2019 Oct 17.

Department of Surgery, LiKaShing Knowledge Institute, St Michael's Hospital, Toronto, Canada.

Background & Aims: The province of Ontario, Canada is considering immunohistochemical followed by cascade analyses of all patients who received a diagnosis of colorectal cancer (CRC) at an age younger than 70 years to identify individuals with Lynch syndrome. We evaluated the costs and benefits of testing for Lynch syndrome and determined the optimal surveillance interval for first-degree relatives (FDRs) found to have Lynch syndrome.

Methods: We developed a patient flow diagram to determine costs and yield of immunohistochemical testing for Lynch syndrome in CRC cases and, for those found to have Lynch syndrome, their FDRs, accounting for realistic uptake. Subsequently, we used the MISCAN-colon model to compare costs and benefits of annual, biennial, and triennial surveillance in FDRs identified with Lynch syndrome vs colonoscopy screening every 10 years (usual care for individuals without a diagnosis of Lynch syndrome).

Results: Testing 1000 CRC cases was estimated to identify 20 CRC index cases and 29 FDRs with Lynch syndrome at a cost of $310,274. Despite the high cost of Lynch syndrome tests, offering the FDRs with Lynch syndrome biennial colonoscopy surveillance was cost-effective at $8785 per life-year gained compared with usual care because of a substantial increase in life-years gained (+122%) and cost savings in CRC care. Triennial surveillance was more costly and less effective, and annual surveillance showed limited additional benefit compared with biennial surveillance.

Conclusions: Immunohistochemical testing for Lynch syndrome in persons younger than 70 years who received a diagnosis of CRC and then testing FDRs of those found to have Lynch syndrome provide a good balance between costs and long-term benefits. Colonoscopy surveillance every 2 years is the optimal surveillance interval for patients with Lynch syndrome.
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http://dx.doi.org/10.1016/j.cgh.2019.10.021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7162709PMC
November 2020

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a clinical practice guideline.

BMJ 2019 Oct 2;367:l5515. Epub 2019 Oct 2.

Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, Canada.

Clinical Question: Recent 15-year updates of sigmoidoscopy screening trials provide new evidence on the effectiveness of colorectal cancer screening. Prompted by the new evidence, we asked: "Does colorectal cancer screening make an important difference to health outcomes in individuals initiating screening at age 50 to 79? And which screening option is best?"

Current Practice: Numerous guidelines recommend screening, but vary on recommended test, age and screening frequency. This guideline looks at the evidence and makes recommendations on screening for four screening options: faecal immunochemical test (FIT) every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy.

Recommendations: These recommendations apply to adults aged 50-79 years with no prior screening, no symptoms of colorectal cancer, and a life expectancy of at least 15 years. For individuals with an estimated 15-year colorectal cancer risk below 3%, we suggest no screening (weak recommendation). For individuals with an estimated 15-year risk above 3%, we suggest screening with one of the four screening options: FIT every year, FIT every two years, a single sigmoidoscopy, or a single colonoscopy (weak recommendation). With our guidance we publish the linked research, a graphic of the absolute harms and benefits, a clear description of how we reached our value judgments, and linked decision aids.

How This Guideline Was Created: A guideline panel including patients, clinicians, content experts and methodologists produced these recommendations using GRADE and in adherence with standards for trustworthy guidelines. A linked systematic review of colorectal cancer screening trials and microsimulation modelling were performed to inform the panel of 15-year screening benefits and harms. The panel also reviewed each screening option's practical issues and burdens. Based on their own experience, the panel estimated the magnitude of benefit typical members of the population would value to opt for screening and used the benefit thresholds to inform their recommendations.

The Evidence: Overall there was substantial uncertainty (low certainty evidence) regarding the 15-year benefits, burdens and harms of screening. Best estimates suggested that all four screening options resulted in similar colorectal cancer mortality reductions. FIT every two years may have little or no effect on cancer incidence over 15 years, while FIT every year, sigmoidoscopy, and colonoscopy may reduce cancer incidence, although for FIT the incidence reduction is small compared with sigmoidoscopy and colonoscopy. Screening related serious gastrointestinal and cardiovascular adverse events are rare. The magnitude of the benefits is dependent on the individual risk, while harms and burdens are less strongly associated with cancer risk.

Understanding The Recommendation: Based on benefits, harms, and burdens of screening, the panel inferred that most informed individuals with a 15-year risk of colorectal cancer of 3% or higher are likely to choose screening, and most individuals with a risk of below 3% are likely to decline screening. Given varying values and preferences, optimal care will require shared decision making.
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http://dx.doi.org/10.1136/bmj.l5515DOI Listing
October 2019

Colorectal cancer screening with faecal immunochemical testing, sigmoidoscopy or colonoscopy: a microsimulation modelling study.

BMJ 2019 Oct 2;367:l5383. Epub 2019 Oct 2.

Erasmus MC, University Medical Center Rotterdam, Department of Public Health, Rotterdam, the Netherlands.

Objective: To estimate benefits and harms of different colorectal cancer screening strategies, stratified by (baseline) 15-year colorectal cancer risk.

Design: Microsimulation modelling study using MIcrosimulation SCreening ANalysis-Colon (MISCAN-Colon).

Setting: A parallel guideline committee ( Rapid Recommendations) defined the time frame and screening interventions, including selection of outcome measures.

Population: Norwegian men and women aged 50-79 years with varying 15-year colorectal cancer risk (1-7%).

Comparisons: Four screening strategies were compared with no screening: biennial or annual faecal immunochemical test (FIT) or single sigmoidoscopy or colonoscopy at 100% adherence.

Main Outcome Measures: Colorectal cancer mortality and incidence, burdens, and harms over 15 years of follow-up. The certainty of the evidence was assessed using the GRADE approach.

Results: Over 15 years of follow-up, screening individuals aged 50-79 at 3% risk of colorectal cancer with annual FIT or single colonoscopy reduced colorectal cancer mortality by 6 per 1000 individuals. Single sigmoidoscopy and biennial FIT reduced it by 5 per 1000 individuals. Colonoscopy, sigmoidoscopy, and annual FIT reduced colorectal cancer incidence by 10, 8, and 4 per 1000 individuals, respectively. The estimated incidence reduction for biennial FIT was 1 per 1000 individuals. Serious harms were estimated to be between 3 per 1000 (biennial FIT) and 5 per 1000 individuals (colonoscopy); harms increased with older age. The absolute benefits of screening increased with increasing colorectal cancer risk, while harms were less affected by baseline risk. Results were sensitive to the setting defined by the guideline panel. Because of uncertainty associated with modelling assumptions, we applied a GRADE rating of low certainty evidence to all estimates.

Conclusions: Over a 15 year period, all screening strategies may reduce colorectal cancer mortality to a similar extent. Colonoscopy and sigmoidoscopy may also reduce colorectal cancer incidence, while FIT shows a smaller incidence reduction. Harms are rare and of similar magnitude for all screening strategies.
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http://dx.doi.org/10.1136/bmj.l5383DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774435PMC
October 2019

A Quarter of Participants With Advanced Neoplasia Have Discordant Results From 2-Sample Fecal Immunochemical Tests for Colorectal Cancer Screening.

Clin Gastroenterol Hepatol 2020 Jul 26;18(8):1805-1811.e1. Epub 2019 Sep 26.

Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address:

Background & Aims: Some colorectal cancer (CRC) screening programs use 2-sample fecal immunochemical tests (FITs). We aimed to assess advanced neoplasia (AN) yield of 2 different FIT assays performed on the same bowel movement and have discordant results.

Methods: We conducted a large prospective comparative accuracy study within the Dutch national CRC screening program to evaluate 2 quantitative FIT assays (FOB-Gold, Sentinel, Italy and OC-Sensor, Eiken, Japan) with comparable performance characteristics. We asked 42,179 screening-naïve individuals, 55-75 years old, to perform both tests on the same bowel movement, from May 2016 through March 2017. Participants with ≥1 positive test result (≥15 μg hemoglobin/gram feces) were invited for colonoscopy examination. Detection of AN by colonoscopy was the reference standard.

Results: A total of 21,078 participants (50% participation rate) were included. FIT results were both negative for 19,032 participants (90%), both positive for 1163 participants (5.5%), and discordant for 883 participants (4.2%). AN was detected in 500 participants with 2 positive FIT results (43%) compared to 187 with discordant FIT results (21%) (p < .001). Of the 687 participants found to have AN by colonoscopy, 187 had only 1 positive FIT result (27%).

Conclusion: In a large 2-sample FIT-based CRC screening study, more than a quarter of participants in whom AN was detected by colonoscopy in the first screening round had discordant FIT results. AN was detected in one-fifth of those with FIT discordance. Participants with discordant results from 2 FITs should undergo colonoscopy. (www.trialregister.nl; no. NTR5874).
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http://dx.doi.org/10.1016/j.cgh.2019.09.024DOI Listing
July 2020