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
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
Jonge, L. de; Schootbrugge-Vandermeer, H.J. van de; Breekveldt, E.C.H.; Spaander, M.C.W.; Vuuren, H.J. van; Kemenade, F.J. van; ... ; Lansdorp-Vogelaar, I. 2022
Objective: The COVID-19 pandemic forced colorectal cancer (CRC) screening programs to downscale their colonoscopy capacity. In this study, we assessed strategies to deal with temporary restricted... Show moreObjective: The COVID-19 pandemic forced colorectal cancer (CRC) screening programs to downscale their colonoscopy capacity. In this study, we assessed strategies to deal with temporary restricted colonoscopy capacity in a FIT-based CRC screening program while aiming to retain the maximum possible preventive effect of the screening program. Design: We simulated the Dutch national CRC screening program inviting individuals between ages 55 and 75 for biennial FIT using the MISCAN-Colon model including the 3-month disruption in the first half of 2020 due to the COVID-19 pandemic. For the second half of 2020 and 2021, we simulated three different strategies for the total target population: 1) increasing the FIT cut-off, 2) skipping one screening for specific screening ages, and 3) extending the screening interval. We estimated the impact on required colonoscopy capacity in 2020-2021 and life years (LYs) lost in the long-term. Results: Increasing the FIT cut-off, skipping screening ages and extending the screening interval resulted in a maximum reduction of 25,100 (-17.0%), 16,100(-10.9%) and 19,000 (-12.9%) colonoscopies, respectively. Modelling an increased FIT cut-off, the number of LYs lost ranged between 1,400 and 4,400. Skipping just a single screening age resulted in approximately 2,700 LYs lost and this was doubled in case of skipping two screening ages. Extending the screening interval up to 34 months had the smallest impact on LYs lost (up to 1,100 LYs lost). Conclusion: This modelling study shows that to anticipate on restricted colonoscopy capacity, temporarily extending the screening interval retains the maximum possible preventive effect of the CRC screening program. 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
Kortlever, T.L.; Jonge, L. de; Wisse, P.H.A.; Seriese, I.; Otto-Terlouw, P.; Leerdam, M.E. van; ... ; Lansdorp-Vogelaar, I. 2021
The COVID-19 pandemic has affected many healthcare services worldwide. Like many other nations, the Netherlands experienced large numbers of individuals affected by COVID-19 in 2020, leading to... Show moreThe COVID-19 pandemic has affected many healthcare services worldwide. Like many other nations, the Netherlands experienced large numbers of individuals affected by COVID-19 in 2020, leading to increased demands on hospitals and intensive care units. The Dutch Ministry of Health decided to suspend the Dutch biennial fecal immunochemical test (FIT) based colorectal cancer (CRC) screening program from March 16, 2020. FIT invitations were resumed on June 3. In this study, we describe the short-term effects of this suspension on a myriad of relevant screening outcomes. As a result of the suspension, a quarter of the individuals due for screening between March and November 2020 had not received their invitation for FIT screening by November 30, 2020. Furthermore, 57.8% of those who received a consecutive FIT between the restart and November 30, 2020, received it outside the upper limit of the standard screening interval (26 months). Median time between positive FIT and colonoscopy did not change as a result of the pandemic. Participation rates of FIT screening and follow-up colonoscopy in the months just before and during the suspension were significantly lower than expected, but returned to normal levels after the suspension. Based on the anticipated 2020 cohort size, we estimate that the number of individuals with advanced neoplasia currently detected up until November 2020 was 31.2% lower compared to what would have been expected without a pandemic. Future studies should monitor the impact on long-term screening outcomes as a result of the pandemic. Show less
