Objective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design:... Show moreObjective: To assess the impact of delayed invitation on screen-detected and interval colorectal cancers (CRC) within a faecal immunochemical testing (FIT)-based CRC screening programme. Design: All individuals that participated in 2017 and 2018 with a negative FIT and were eligible for CRC screening in 2019 and 2020 were included using individual-level data. Multivariable logistic regression analyses were used to assess the association between either the different time periods (ie, 'before', 'during' and 'after' the first COVID-19 wave) or the invitation interval on screen-detected and interval CRCs. Results: Positive predictive value for advanced neoplasia (AN) was slightly lower during (OR=0.83) and after (OR=0.92) the first COVID-19 wave, but no significant difference was observed for the different invitation intervals. Out of all individuals that previously tested negative, 84 (0.004%) had an interval CRC beyond the 24 months since their last invitation. The time period of invitation as well as the extended invitation interval was not associated with detection rates for AN and interval CRC rate. Conclusion: The impact of the first COVID-19 wave on screening yield was modest. A very small proportion of the FIT negatives had an interval CRC possibly due to an extended interval, which potentially could have been prevented if they had received the invitation earlier. Nonetheless, no increase in interval CRC rate was observed, indicating that an extended invitation interval up to 30 months had no negative impact on the performance of the CRC screening programme and a modest extension of the invitation interval seems an appropriate intervention. Show less
Breekveldt, E.C.H.; Toes-Zoutendijk, E.; Jonge, L. de; Spaander, M.C.W.; Dekker, E.; Kemenade, F.J. van; ... ; Lansdorp-Vogelaar, I. 2023
Background In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is... Show moreBackground In 2014, the national population-based colorectal cancer (CRC) screening program was implemented in the Netherlands. Biennial fecal immunochemical testing (FIT) for hemoglobin (Hb) is used at a cut-off of 47 mu g Hb per gram feces. The CRC screening program successfully started, with high participation rates and yield of screening. Now that the program has reached a steady state, there is potential to further optimize the program. Previous studies showed that prior fecal Hb (f-Hb) concentrations just below the FIT cut-off are associated with a higher risk for detection of advanced neoplasia (AN) at subsequent screening rounds. We aim to achieve a better balance between the harms and benefits of CRC screening by offering participants tailored invitation intervals based on prior f-Hb concentrations after negative FIT. Methods This mixed-methods study will be performed within the Dutch national CRC screening program and will consist of: (1) a randomized controlled trial (RCT), (2) focus group studies, and (3) decision modelling. The primary outcome is the yield of AN per screened individual in personalized screening vs. uniform screening. Secondary outcomes are perspectives on, acceptability of and adherence to personalized screening, as well as long-term outcomes of personalized vs. uniform screening. The RCT will include 20,000 participants of the Dutch CRC screening program; 10,000 in the intervention and 10,000 in the control arm. The intervention arm will receive a personalized screening interval based on the prior f-Hb concentration (1, 2 or 3 years). The control arm will receive a screening interval according to current practice (2 years). The focus group studies are designed to understand individuals' perspectives on and acceptability of personalized CRC screening. Results of the RCT will be incorporated into the MISCAN-Colon model to determine long-term benefits, harms, and costs of personalized vs. uniform CRC screening. Discussion The aim of this study is to evaluate the yield, feasibility, acceptability and (cost-) effectiveness of personalized CRC screening through tailored invitation intervals based on prior f-Hb concentrations. This knowledge may be of guidance for health policy makers and may provide evidence for implementing personalized CRC screening in The Netherlands and/or other countries using FIT as screening modality. Show less
Background: Advanced serrated polyps (ASPs) have a comparable risk to advanced adenomas for progression to colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on... Show moreBackground: Advanced serrated polyps (ASPs) have a comparable risk to advanced adenomas for progression to colorectal cancer (CRC). The yield of most CRC screening programs, however, is based on advanced adenomas and CRC only. We assessed the ASP detection rate, and positive predictive value (PPV) including ASPs in a fecal immunochemical test (FIT)-based screening program. Methods: We analyzed the findings of follow-up colonosco pies of FIT-positive screenees in the Dutch CRC screening program from 2014 until 2020. Data were retrieved from the national screening and pathology database. An ASP was defined as any serrated polyp of z 10 mm, sessile serrated lesion with dysplasia, or traditional serrated adenoma. The ASP detection rate was defined as the proportion of colonoscopies with >= 1 ASP. PPV was originally defined as the proportion of individuals with a CRC or advanced adenoma. The updated PPV definition included CRCs, advanced adenomas, and/or ASPs. Results: 322 882 colonoscopies were included in the analyses. The overall detection rate of ASPs was 5.9%. ASPs were detected more often in women than men (6.3% vs. 5.6%; P < 0.001). ASP detection rates in individuals aged 55-59, 60-64, 65-69, and 70+ were 5.2%, 6.1 %, 6.1 %, and 5.9%, respectively (P < 0.001). The PPV for CRCs and advanced adenomas was 41.1 % and increased to 43.8% when including ASPs. The PPV increase was larger in women than in men (3.2 vs. 2.4 percentage points). Conclusions: 5.9% of FIT-positive screenees had ASPs, but half of these were detected in combination with a CRC or advanced adenoma. Therefore, including ASPs results in a small increase in the yield of FIT-based screening. Show less
Breekveldt, E.C.H.; Toes-Zoutendijk, E.; Schootbrugge-vandermeer, H.J. van de; Jonge, L. de; Kooyker, A.I.; Spaander, M.C.W.; ... ; Lansdorp-Vogelaar, I. 2022
The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of... Show moreThe interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT-based CRC screening program in the Netherlands, using data from individuals who participated in FIT-screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT-negative participants (< 47 mu g Hb/g feces [mu g/g]), FIT-sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f-Hb). FIT-sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f-Hb affects probability of detecting interval CRC, adjusted for sex- and age-differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT-sensitivity based on the detection method was 84.4% (95%CI 83.8-85.0) in the first and 73.5% (95% CI 71.8-75.2) in the second screening round. The proportional incidence method resulted in a FIT-sensitivity of 76.4% (95%CI 73.3-79.6) in the first and 79.1% (95%CI 73.7-85.3) in the second screening round. After one negative FIT, participants with f-Hb just below the cut-off (> 40-46.9 mu g/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0-20.4) than had participants with unmeasurable f-Hb (0-2.6 mu g/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8-17.6) for participants with f-Hb just below the cut-off compared with participants with unmeasurable f-Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT-sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk-stratified CRC screening based on prior f-Hb. Show less
Breekveldt, E.C.H.; Toes-Zoutendijk, E.; Schootbrugge-vandermeer, H.J. van de; Jonge, L. de; Kooyker, A.I.; Spaander, M.C.W.; ... ; Lansdorp-Vogelaar, I. 2022
The interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of... Show moreThe interval colorectal cancer (CRC) rate after negative fecal immunochemical testing (FIT) is an important quality indicator of CRC screening programs. We analyzed the outcomes of two rounds of the FIT-based CRC screening program in the Netherlands, using data from individuals who participated in FIT-screening from 2014 to 2017. Data of individuals with one prior negative FIT (first round) or two prior negative FITs (first and second round) were included. Outcomes included the incidence of interval CRC in FIT-negative participants (<47 μg Hb/g feces [μg/g]), FIT-sensitivity, and the probability of detecting an interval CRC by fecal hemoglobin concentration (f-Hb). FIT-sensitivity was estimated using the detection method and the proportional incidence method (based on expected CRC incidence). Logistic regression analysis was performed to estimate whether f-Hb affects probability of detecting interval CRC, adjusted for sex- and age-differences. Incidence of interval CRC was 10.4 per 10 000 participants after the first and 9.6 after the second screening round. FIT-sensitivity based on the detection method was 84.4% (95%CI 83.8-85.0) in the first and 73.5% (95% CI 71.8-75.2) in the second screening round. The proportional incidence method resulted in a FIT-sensitivity of 76.4% (95%CI 73.3-79.6) in the first and 79.1% (95%CI 73.7-85.3) in the second screening round. After one negative FIT, participants with f-Hb just below the cut-off (>40-46.9 μg/g) had a higher probability of detecting an interval CRC (OR 16.9; 95%CI: 14.0-20.4) than had participants with unmeasurable f-Hb (0-2.6 μg/g). After two screening rounds, the odds ratio for interval CRC was 12.0 (95%CI: 7.8-17.6) for participants with f-Hb just below the cut-off compared with participants with unmeasurable f-Hb. After both screening rounds, the Dutch CRC screening program had a low incidence of interval CRC and an associated high FIT-sensitivity. Our findings suggest there is a potential for further optimizing CRC screening programs with the use of risk-stratified CRC screening based on prior f-Hb. Show less
Meester, R.G.S.; Schootbrugge-vandermeer, H.J. van de; Breekveldt, E.C.H.; Jonge, L. de; Toes-Zoutendijk, E.; Kooyker, A.; ... ; Dutch colorectal canc screening working group 2022
Objectives: To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC).... Show moreObjectives: To examine the prognostic potential of repeated faecal haemoglobin (F-Hb) concentration measurements in faecal immunochemical test (FIT)-based screening for colorectal cancer (CRC). Design: Prognostic model. Setting: Dutch biennial FIT-based screening programme during 2014-2018. Participants: 265 881 participants completing three rounds of FIT, with negative test results (F-Hb <47 mu g Hb/g faeces) in rounds 1 and 2. Interventions: Colonoscopy follow-up in participants with a positive FIT (F-Hb >= 47 mu g Hb/g faeces). Main outcomes: We evaluated prognostic models for detecting advanced neoplasia (AN) and CRC in round 3, with as predictors, participant age, sex, F-Hb in rounds 1 and 2, and categories/combinations/non-linear transformations of F-Hb. Primary evaluation criteria included: risk prediction accuracy (calibration), discrimination of participants with versus without AN or CRC (optimism-adjusted C-statistics, range 0.5-1.0), the degree of risk stratification and C-statistics in external validation. Results: Among study participants, 8806 (3.3%) had a positive FIT result, 3254 (1.2%) had AN detected and 557 (0.2%) had cancer. F-Hb concentrations in rounds 1 and 2 were the strongest outcome predictors, with adjusted ORs of up to 9.4 (95% CI 7.5 to 11.7) for the highest F-Hb category. Risk predictions matched the observed risk for most participants (calibration intercept -0.008 to -0.099; slope 0.982-0.998), and discriminated participants with versus without AN or CRC with C-statistics of 0.78 (95% CI 0.77 to 0.79) and 0.73 (95% CI 0.71 to 0.75), respectively. The predicted risk ranged from 0.4% to 36.7% for AN and from 0.0% to 5.5% for CRC across participants. In external validation, the model retained similar discrimination accuracy for AN (C-statistic 0.77, 95% CI 0.66 to 0.87) and CRC (C-statistic 0.78, 95% CI 0.66 to 0.91). Conclusion: Participants at lower versus higher risk of future AN or CRC can be accurately identified based on their age, sex and particularly, prior F-Hb concentrations. Risk stratification should be considered based on this information. Show less
Background In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a... Show moreBackground In 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 mu g haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme.Methods We did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010-19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014-18 in patients aged 55-75 years.Findings Between Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214.3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259.2 per 100 000 population in 2015, and subsequently decreased to 181.5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117.0 per 100 000 population in 2013 and increased to 122.8 per 100 000 population in 2015; this rate then decreased to 94.7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87.5 deaths per 100 000 population in 2010 to 64.8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48.6% vs 35.2%) and to be detected at an early stage (I or II; 66. 7% vs 46.2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this fmding persisted when stage I CRCs were analysed separately.Interpretation After introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. Copyright (C) 2021 Elsevier Ltd. All rights reserved. Show less
BackgroundIn 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a... Show moreBackgroundIn 2014, a population-based colorectal cancer (CRC) screening programme was stepwise implemented in the Netherlands comprising faecal immunochemical testing once every 2 years, with a cutoff value for positivity of 47 μg haemoglobin per g faeces. We aimed to assess CRC incidence, mortality, tumour characteristics, and treatment before and after introduction of this screening programme.MethodsWe did a retrospective, observational, population-based study in the Netherlands and gathered CRC incidence data from the Netherlands Cancer Registry from Jan 1, 2010, to Dec 31, 2019, in people aged 55 years or older. Patients with a CRC diagnosis between Jan 1, 2014, and Dec 31, 2018, in the Netherlands Cancer Registry were linked with the nationwide registry of histopathology and cytopathology (PALGA) to identify mode of detection (ie, screening-detected vs clinically detected). We calculated age-standardised CRC incidence rates and used data from Statistics Netherlands to calculate CRC-related mortality in 2010–19. We compared localisation, stage distribution, and treatment of screening-detected CRCs with clinically detected CRCs diagnosed in 2014–18 in patients aged 55–75 years.FindingsBetween Jan 1, 2010, and Dec 31, 2019, 125 215 CRCs were diagnosed in individuals aged 55 years or older and were included in the analyses for CRC incidence. Before the introduction of the screening programme, the age-standardised CRC incidence rate was 214·3 per 100 000 population in 2013 in people aged 55 years or older. After the introduction of the screening programme, this rate initially increased to 259·2 per 100 000 population in 2015, and subsequently decreased to 181·5 per 100 000 population in 2019. Age-standardised incidence rates for advanced CRCs (stage III and IV) were 117·0 per 100 000 population in 2013 and increased to 122·8 per 100 000 population in 2015; this rate then decreased to 94·7 per 100 000 population in 2018. Age-standardised CRC mortality decreased from 87·5 deaths per 100 000 population in 2010 to 64·8 per 100 000 population in 2019. Compared with clinically detected CRCs, screening-detected CRCs were more likely to be located in the left side of the colon (48·6% vs 35·2%) and to be detected at an early stage (I or II; 66·7% vs 46·2%). Screening-detected CRCs were more likely to be treated by local excision compared with clinically detected CRCs, and this finding persisted when stage I CRCs were analysed separately.InterpretationAfter introduction of this national screening programme, a decrease in overall and advanced-stage CRC incidence was observed. In view of this observation, together with the observed shift to detection at earlier stages and more screening-detected CRCs being treated by local excision, we might cautiously conclude that, in the long-term, faecal immunochemical testing-based screening could ultimately lead to a decrease in CRC-related morbidity and mortality. Show less
BACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and... Show moreBACKGROUND & AIMS: We evaluated the incidence of interval cancers between the first and second rounds of colorectal cancer (CRC) screening with the FOB-Gold fecal immunochemical test (FIT), and the effects of different cutoff values and patient sex and age.METHODS: We collected data from participants in a population-based CRC screening program in the Netherlands who had a negative result from a first-round of FIT screening. We calculated the cumulative incidence of interval cancer after a negative result from a FIT and the sensitivity of the FIT for detection of CRC at a low (15 mu g Hb/g feces) and high (47 mu g Hb/g feces) cutoff value.RESULTS: Among the 485,112 participants with a negative result from a FIT, 544 interval cancers were detected; 126 were in the 111,800 participants with negative results from a FIT with the lowcutoff value and 418 were in the 373,312 FIT participants with negative results from a FIT with the high cutoff value. The mean age of participants tested with the low cutoff value was 72.0 years and the mean age of participants tested the high cutoff value was 66.7 years. The age-adjusted 2-year cumulative incidence of interval cancer after a negative result from a FIT were 9.5 per 10,000 persons at the low cutoff value vs 13.8 per 10,000 persons at the high cutoff value (P < .005). The age-adjusted sensitivity of the FIT for CRC were 90.5% for the low cutoff value vs 82.9% for the high cutoff (P < .0001). The FIT identified men with CRC with 87.4% sensitivity and women with CRC with 82.6% sensitivity (P < .001).CONCLUSIONS: In an analysis of data from a FIT population-based screening program in the Netherlands, we found that incidence of interval CRC after a negative result from a FIT to be low. Although the sensitivity of detection of CRC decreased with a higher FIT cutoff value, it remained above 80%. Show less
