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 ( BMJ 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.

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 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 mg Hb/g feces) and high (47 mg 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 low cutoff 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%.

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.

Background: Microsimulation models are increasingly being used to inform colorectal cancer (CRC) screening recommendations. MISCAN-Colon is an example of such a model, used to inform the Dutch CRC screening program and United States Preventive Services Task Force guidelines. Assessing the validity of these models is essential to provide transparency regarding their performance. In this study we tested the external and predictive validity of MISCAN-Colon. Methods: We validated MISCAN-Colon using the Norwegian Colorectal Cancer Prevention (NORCCAP) trial, a randomized controlled trial that examined the effectiveness of once-only flexible sigmoidoscopy (FS) screening. We simulated the study population and design of the NORCCAP trial in MISCAN-Colon and compared 10- to 12-year model predicted hazard ratios (HRs) for overall and distal CRC incidence and mortality to those observed. In addition, we compared the numbers of screen-detected neoplasia. Finally, we predicted the trial’s future results to allow for the assessment of predictive validity. Results: MISCAN-Colon predicted a HR for overall CRC incidence (0.85), for distal CRC incidence (0.82), for overall CRC mortality (0.68) and for distal CRC mortality (0.62). These were within the limits of the 95% confidence intervals of the NORCCAP trial results. Similar results were observed for the number of screen-detected cancers. The model significantly underestimated the number of screen-detected adenomas. Model-predicted HRs for CRC incidence and mortality up to 15- to 17-years follow-up were 0.84 and 0.72, respectively. Conclusion: Although the underestimation of screen-detected adenomas requires further investigation, MISCAN-Colon is able to make a valid replication of the CRC incidence and mortality reduction of an FS screening trial, which suggests that it can be considered a useful tool to support decision making on CRC screening.

Background. 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. Methods. 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. Results. 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. Conclusions. 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.