FIT-based Colorectal Cancer Screening Research Articles

Detection of colorectal cancer and advanced neoplasia during first surveillance interval after detection of adenomas in fecal immunochemical test cancer screening: a nationwide study.

Adenoma surveillance guidelines are based on non-fecal immunochemical test (FIT)-based screening settings. However, colorectal cancer (CRC) risk may be different in FIT-positive screening populations. We evaluated the CRC and advanced adenoma risk within the recommended surveillance periods in the Danish FIT-based CRC screening program for participants with intermediate or high risk adenomas according to 2010 European guidelines. Furthermore, we estimated CRC risk for those who were not recommended surveillance according to European Society of Gastrointestinal Endoscopy (ESGE) 2020 guidelines. Using nationwide health registries, we identified 17 936 FIT-screening participants from 2014-2017 with adenomas undergoing surveillance (high risk 1 year, intermediate risk 3 years). Participants with a follow-up examination were included (N = 10 068). Relative risk (RR) of CRC and advance adenoma was compared between intermediate and high risk groups and between intermediates who were recommended surveillance (S) or no surveillance (NS) according to 2020 ESGE guidelines. During surveillance, CRC occurred in 0.59% of the high risk group and 1.11% of the intermediate risk group (RR 0.53 [95%CI 0.34-0.84]). The high risk group had a 24% increased risk of advanced adenoma. CRC occurred in 1.69% of the intermediateNS group and 0.87% of the intermediateS group (RR 1.94 [95%CI 1.18-3.21]), and RR for advanced adenoma was 1.19 (95%CI 1.03-1.37). CRC detection was lower among participants rated at higher risk at initial CRC screening. Findings at first screen-derived colonoscopy might not be as good a predictor of CRC risk in a FIT-positive screening population.

Modelling the impact of bias in fecal immunochemical testing on long-term outcomes of colorectal cancer screening

BackgroundAs the impact of unmanaged bias (i.e. systematic source of inaccuracy) in fecal immunochemical test (FIT) analytical performance on long-term colorectal cancer (CRC) outcomes is unknown, we assessed the impact bias in FIT performance in an ongoing FIT-based CRC screening program. MethodsThis study consisted of two parts: cross-sectional observational data analysis to estimate change in short-term outcomes and microsimulation modelling to estimate change in long-term outcomes assuming different levels of bias by assuming 15 % lower up to 15 % higher Hemoglobin detected in the stool compared to observed. Two scenarios were considered: bias occurring 1) one-time only, due to the occasional bias associated with the FIT kits used in 2020 and 2) consistently due to a constant bias associated with the FIT kits used from 2020 onwards. ResultsWith a hypothetical bias of −15 % to +15 %, we observed a positivity rate ranging from 6.7 % to 7.8 %, and a detection rate for CRC between 0.65 % and 0.68 %. Single biases in FIT performance resulted in less than 0.1 % change in long-term CRC screening outcomes, while consistent biases resulted in a much larger change (up to 1.4 % in CRC cases and CRC-related deaths and up to 2.07 % in total costs). Detecting lower Hemoglobin concentrations resulted in a relatively larger change on long-term CRC outcomes in comparison to positive bias. ConclusionsBecause of the substantial impact of consistent FIT bias, it is important to set evidence-based acceptance criteria of bias on long-term CRC screening outcomes and in particular, the introduction of an asymmetrical or upward shifted tolerance interval for FIT bias.

Comparing a fecal immunochemical test and circulating tumor DNA blood test for colorectal cancer screening adherence.

Colorectal cancer (CRC) screening programs are most effective at reducing disease incidence and mortality through sustained screening participation. A novel blood test modality is being explored for CRC screening, but it is unclear whether it will provide sustained screening participation. This study aimed to investigate whether a circulating tumor DNA (ctDNA) blood test improved CRC screening re-participation when compared with a fecal immunochemical test (FIT) and to define the predictors of sustained CRC screening in an Australian population. South Australians who initially participated in CRC screening using a ctDNA blood test (n=36) or FIT (n=547) were offered the same CRC screening test approximately 2years later through an extended phase of a randomized controlled trial. Surveys collected demographic, psychosocial, and clinical information. Predictors of CRC screening re-participation were explored using chi-square, Wilcoxon tests, and logistic regression. Participants offered a second ctDNA blood test were equally likely to re-participate in CRC screening as those who completed a FIT in the first round and who were offered the same test (61% vs 66% re-participation respectively, P=0.6). CRC fatalism, health activation, and self-efficacy were associated with repeated screening participation. Test awareness was predictive of repeated FIT-based CRC screening. Targeted interventions to improve CRC screening awareness and increase patient health activation may improve CRC screening adherence. A ctDNA blood test may be a suitable CRC screening option to maintain CRC screening adherence in people who do not participate in screening with FIT.

Feasibility and Colonoscopy Yield Using the Fecal Immunochemical Test (FIT)-Based Colorectal Cancer Screening in a Latin America Country

Background and aimsOrganized colorectal cancer (CRC) is not widely practiced in Latin America and the results of regional studies may help overcome barriers for implementation of national screening programs. We aimed to describe the implementation and findings of a fecal immunochemical test (FIT)-based program in Brazil. MethodsIn a prospective population-based study, asymptomatic individuals (50 to 75 years-old) from Sao Paulo city were invited to undergo FIT for CRC screening. Participants with positive FIT (>10 μg Hb/g feces) were referred for colonoscopy. Subjects were classified into groups according to the presence of CRC, precursor lesions, and other benign findings, possibly related to bleeding. ResultsOf a total of 9,881 subjects, 7.8% had positive FIT and colonoscopy compliance was 68.9% (n=535). Boston scale was considered adequate in 99% and cecal intubation rate was 99.4%. CRC was diagnosed in 5.9% of the cases, adenoma in 63.2%, advanced adenoma (AA) in 31.4%, and advanced neoplasia (AN) in 33.0%. Age was positively associated with CRC (p=0.03). Higher FIT concentrations were associated with increased detection of CRC (p<0.008), AA (p<0.001), and AN (p<0.001). ConclusionImplementation of a FIT-based CRC screening program was feasible in a low-resource setting, and there was a high yield for neoplasia in individuals with a positive FIT. This approach could be used as a model to plan and disseminate organized CRC screening more broadly in Brazil and Latin America.

Post-colonoscopy colorectal cancers in a national fecal immunochemical test-based colorectal cancer screening program.

Post-colonoscopy colorectal cancers (PCCRCs) decrease the effect of colorectal cancer (CRC) screening programs. To enable PCCRC incidence reduction in the long-term, we classified PCCRCs diagnosed after colonoscopies performed in a fecal immunochemical test (FIT)-based screening program. PCCRCs diagnosed after colonoscopies performed between 2014-2016 for a positive FIT in the Dutch CRC screening program were included. PCCRCs were categorized according to the World Endoscopy Organization consensus statement into (a) interval PCCRC (diagnosed before the recommended surveillance); (b) non-interval type A (diagnosed at the recommended surveillance interval); (c) non-interval type B (diagnosed after the recommended surveillance interval); or (d) non-interval type C (diagnosed after the intended recommended surveillance interval, with surveillance not implemented owing to co-morbidity). The most probable etiology was determined by root-cause analysis. Tumor stage distributions were compared between categories. 116362 colonoscopies were performed after a positive FIT with 9978 screen-detected CRCs. During follow-up, 432 PCCRCs were diagnosed. The 3-year PCCRC rate was 2.7%. PCCRCs were categorized as interval (53.5%), non-interval type A (14.6%), non-interval type B (30.6%), and non-interval type C (1.4%). The most common etiology for interval PCCRCs was possible missed lesion with adequate examination (73.6%); they were more often diagnosed at an advanced stage (stage III/IV; 53.2%) compared with non-interval type A (15.9%; P<0.001) and non-interval type B (40.9%; P=0.03) PCCRCs. The 3-year PCCRC rate was low in this FIT-based CRC screening program. Approximately half of PCCRCs were interval PCCRCs. These were mostly caused by missed lesions and were diagnosed at a more advanced stage. This emphasizes the importance of high quality colonoscopy with optimal polyp detection.

Low Colorectal Cancer Risk After Resection of High-Risk Pedunculated Polyps

IntroductionPost-Faecal Immunochemical Test (FIT) colonoscopy represents a setting with an enriched prevalence of advanced adenomas. Due to an expected higher risk of Colorectal Cancer (CRC), post-polypectomy surveillance is recommended, generating a substantially increased load on endoscopy services. The aim of our study was to investigate post-polypectomy CRC risk in a screening population of FIT+ subjects after resection of low- (LRA) or high-risk adenomas (HRA). MethodsWe retrieved data from a cohort of patients undergoing post-polypectomy surveillance within a FIT-based CRC screening program in Italy between 2002 and 2017 and followed-up to December 2021. Main outcomes were post-polypectomy CRC incidence and mortality risks according to type of adenoma (LRA/HRA) removed at colonoscopy as well as morphology, size, dysplasia and location of the index lesion. We adopted as comparators FIT+/colonoscopy negative and FIT negative patients. The absolute risk was calculated as the number of incident CRCs per 100,000 person-years of follow-up. We used Cox multivariable regression models to identify associations between CRC risks and patient- and polyp-related variables. ResultsOverall, we included 87,248 post-FIT+ colonoscopies (133 endoscopists). Of these, 42,899 (49.2%) were negative, 21,650 (24.8%) had a LRA and 22,709 (26.0%) a HRA. After a median follow-up of 7.25 years, a total of 635 CRCs were observed. For patients with LRAs, CRC incidence (Hazard Ratio [HR] 1.18, 95% Confidence Interval [CI] 0.92-1.53) was not increased compared to the FIT+/colonoscopy negative group, while for HRAs a significant increase in CRC incidence (HR 1.53, 95% CI 1.14-2.04) was found. The presence of one or more risk factors among proximal location, non-pedunculated morphology and high-grade dysplasia explained most of this excess CRC risk in the HRA group (HR 1.85, 95% CI 1.36-2.52). Patients with only distal pedunculated polyps without HGD, representing 39.2% of HRA, did not have increased risk compared to the FIT-negative group (HR 0.87, 95% CI 0.59 - 1.28). ConclusionsCRC incidence is significantly higher in patients with high-risk adenomas diagnosed at colonoscopy. However, such excess risk does not appear to apply to patients with only distal pedunculated polyps without HGD, an observation that could potentially reducethe burden of surveillance in FIT programs.

Examining the Sustainability of Core Capacity and Evidence-Based Interventions for FIT-Based CRC Screening: California Colorectal Cancer Control Program.

We examined the extent to which funded satellite clinics could sustain the California Colon Cancer Control Program (C4P) strategies implemented in health systems to increase uptake of the fecal immunochemical test (FIT) or immunochemical fecal occult blood test (iFOBT) for colorectal cancer (CRC) screening in the absence of future C4P funds. Seven health systems consisting of 38 satellite clinics participated in C4P to examine the sustainability of the program in the absence future Centers for Disease Control and Prevention (CDC) funding. Quantitative and qualitative methods with a close and open-ended survey approach, and a prospective cohort design were used to examine the sustainability of the C4P in health systems. A total of 61% of satellite clinics could not sustain funding stability. Only 26% could sustain funding stability. About, 71%, 26%, and 21% of the satellite clinics could sustain the small media platform, patient navigation services, and community health workers (CHWs), respectively. All the satellite clinics sustained the provider reminder system and professional development. Roughly, 71% and 42% of funded satellite clinics could not sustain the patient navigators and CHWs, respectively. The satellite clinics that could sustain funding stability, sustained patient navigation services and CHWs. Health systems that could not sustain funding stability, could not sustain patient navigation services and CHWs. Qualitatively, the need to support uninsured priority populations, health educators, patient navigators, care coordination activities, outreach services, and provision of enhanced services emerged. The need to support enhanced quality measures, expansion of funding, Medi-Cal Public Hospital Redesign and Incentive coverage, health plan, community linkages, resource sharing, and best practices specifically on CRC screening emerged. Themes such as automated reminder, limited personalized care delivery and capacity, transportation barriers, staff salary, expansion of care through patient navigation, and culturally appropriate media campaign also emerged. Overall, to address sustainability barriers, funding stability should be maintained in the health systems.

A digital intake tool to avert outpatient visits in a FIT-based colorectal cancer screening population: study protocol of a multicentre, prospective non-randomized trial - the DIT-trial

BackgroundCurrently all participants of the Dutch colorectal cancer (CRC) screening program with a positive faecal immunochemical test (FIT) are seen at the outpatient clinic to assess their health status, receive information on colonoscopy and CRC risk, and provide informed consent. However, for many patients this information could probably also safely be exchanged in an online setting, in order to reduce the burden for patients, healthcare system, and environment. In this study we will evaluate if a face-to-face pre-colonoscopy consultation can be replaced by a Digital Intake Tool (DIT) in a CRC screening population.MethodsThis is a prospective multicentre single-arm, non-randomized study with a non-inferiority design. The DIT will triage a total of 1000 participants and inform them about CRC risk, colonoscopy, sedation, and provide bowel preparation instructions. Participants identified as high-risk (i.e., red-triaged) will be contacted by phone or scheduled for an appointment at the outpatient clinic. The primary outcome measure will be adequate bowel preparation rate, defined as the proportion of participants with a Boston Bowel Preparation (BBPS) score ≥ 6. To compare our primary outcome, we will use colonoscopy data from 1000 FIT positive participants who visited the outpatient clinic for pre-colonoscopy consultation. Secondary outcomes will include participation rate, colonoscopy adherence rate, patient experience in terms of satisfaction and anxiety, knowledge transfer, number of outpatient visits that can be averted by the DIT, and cost-effectiveness of the tool. Ethical approval was obtained from the Medical Ethical Committee of the Erasmus Medical Center (MEC-2021-0098).DiscussionThis study aims to assess if a face-to-face pre-colonoscopy consultation can be replaced by an eHealth assessment and education tool in a FIT-based CRC screening program. In case favourable results are established, the intervention evaluated in this study could significantly impact CRC screening programs, benefiting both patients and healthcare systems on a (inter)national scale. Additionally, it would enable more personalized care as the DIT can be easily customized and made feasible in other languages, thereby enhancing healthcare accessibility.Trial registrationDutch Trial Register: NL9315, date of registration: March 8th, 2021.

Bleeding and Perforation Complications after Follow-Up Colonoscopies in Faecal Immunochemical Test-Based Colorectal Cancer Screening: Insights from a Retrospective Case–Control Study

Monitoring complications of colonoscopies after a positive faecal immunochemical test (FIT-colonoscopies) is crucial in FIT-based colorectal cancer (CRC) screening. We investigated the occurrence of bleeding and perforation post FIT-colonoscopies (2013–2019) in Flanders and the contributing factors. A retrospective case–control study was conducted, including bleeding/perforation cases within 14 days after index colonoscopy, and controls without such events. Bleeding rates dropped from 0.9–1.1% (pre-2017) to 0.3% (2017–2018) and further to 0.05% (2019), while perforation rates remained at 0.05–0.11% (2014–2019). Male gender, polypectomy, general anaesthesia, and recent antiplatelet/antithrombotic drug use increased bleeding odds. Incomplete colonoscopy, polypectomy, general anaesthesia, and recent antiplatelet/antithrombotic drug use raised perforation odds. The endoscopists (n = 16) with highest bleeding rates (top 5%) performed only 6% of total FIT-colonoscopies, yet their patients experienced 45.5% of bleeding events. Similarly, for the top 5% of perforation rates, endoscopists conducting only 4.5% of total FIT-colonoscopy had 49.0% of perforation events occur in their patients. This study sheds light on FIT-colonoscopy-related complications in Flanders, their rates and risk factors. These findings can be incorporated into CRC screening materials and guide interventions to mitigate complications. A central colonoscopy register is currently lacking in Belgium, highlighting the need for its establishment to facilitate recurrent monitoring and evaluation.

Abstract C122: Patient perspectives on factors influencing repeat colorectal cancer screening in a Federally Qualified Health Center

Abstract Background. The life-saving benefits of colorectal cancer (CRC) screening can be maximized only if screening is completed at recommended intervals. The fecal immunochemical test (FIT), an inexpensive stool-based test recommended yearly, is the primary screening modality in many Federally Qualified Health Centers (FQHCs) and remains underutilized. To inform system interventions, we sought to identify patient perspectives on factors that influence the likelihood of repeated FIT screening over time in a large FQHC. Methods. Between September 2022 and March 2023, we conducted semi-structured interviews with patients who were due for FIT screening and completed at least one prior FIT test at a large FQHC that serves a primarily Latino population in Los Angeles County. Our interview guide explored patients’ perceived barriers and facilitators to repeat FIT over time and experiences with FIT clinic processes of care. Audio-recorded interviews were conducted in patients’ preferred language (English or Spanish), transcribed, and translated. Transcripts were coded using ATLAS.ti, and themes were summarized. Results. Among 17 interview participants, the majority were female (82%), Latino (94%), and Spanish-speaking (88%). The median age was 57 years (range 52-70), and 41% had an 8th grade education or less. Interviews revealed that patient, family, and provider/system factors influenced receipt of sequential rounds of annual FIT CRC screening. At the patient level, perceived importance of disease prevention and early detection on the part of patients facilitated proactive engagement in regular screening. Additionally, many patients thought the process of FIT completion and return was easy, although some patients did express low confidence in stool sample collection and time and work constraints impeding in-person FIT return. Another recurrent theme was motivation from family, both direct support (assistance with FIT completion and transportation to clinic) and indirect motivation (an intrinsic desire to stay healthy for family). At the provider/system level, language discordance hindered communication with providers, and in-language FIT instructions and availability of bilingual staff to translate were identified as facilitators. Patient suggestions to improve FIT completion included client text and letter reminders when due for CRC screening; print education that underscores the purpose of screening; and appointment consolidation for cancer and other preventive care screenings. Conclusion. Interventions to improve regular FIT-based CRC screening may benefit from emphasizing the importance of early detection; improving patient knowledge and confidence in how to perform stool sample collection; family support; and language-concordant staff and resources for multi-lingual and medically underserved populations. Citation Format: Narissa J. Nonzee, Beth A. Glenn, Debra Rosen, Genesis Sandoval, Diana Trujillo, Folasade P. May, Alison K. Herrmann, Christine Park, Alicia Lwin, Joanna Quintanilla, Jessica Tuan, Lauren Cai, Roshan Bastani. Patient perspectives on factors influencing repeat colorectal cancer screening in a Federally Qualified Health Center [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr C122.

Value of fecal immunochemical test in colorectal cancer screening

Screening and early diagnosis and treatment have been proven effective in reducing the incidence and mortality of colorectal cancer. Colonoscopy combined with pathological examination is the gold standard for colorectal cancer screening. However, due to the invasiveness, high cost and the need for professional endoscopists of colonoscopy, it is not feasible to directly use this method for mass population screening. Fecal immunochemical test (FIT) is one of the screening techniques recommended by authoritative international guidelines for colorectal cancer screening, and has been widely used in population-based colorectal cancer screening programs in countries around the world. This paper elaborates on the value of FIT in colorectal cancer screening from different aspects, such as the technical principles, the screening efficiency, the screening strategies, and the population effects and benefits. Additionally, it describes the current situation of colorectal cancer screening in China and summarizes the challenges faced in colorectal cancer screening in order to optimize the FIT-based colorectal cancer screening strategies in the population and provide theoretical reference for effective colorectal cancer screening.

The impact on clinical outcomes and healthcare resources from discontinuing colonoscopy surveillance subsequent to low-risk adenoma removal: A simulation study using the OncoSim-Colorectal model.

To estimate the impact on clinical outcomes and healthcare resource use from recommending that patients with 1-2 low-risk adenomas (LRAs) return to routine fecal immunochemical test (FIT) screening instead of surveillance colonoscopy, from a Canadian provincial healthcare system perspective. The OncoSim-Colorectal microsimulation model simulated average-risk individuals eligible for FIT-based colorectal cancer (CRC) screening in Alberta, Canada. We simulated two surveillance strategies that applied to individuals with 1-2 LRAs (<10 mm) removed as part of the average risk CRC screening program: (a) Surveillance colonoscopy (status quo) and (b) return to FIT screening (new strategy); both at 5 years after polypectomy. A 75 ng/mL FIT positivity threshold was used in the base case. The simulations projected average annual CRC outcomes and healthcare resource use from 2023 to 2042. We conducted alternative scenarios and sensitivity analyses on key variables. Returning to FIT screening (versus surveillance colonoscopy) after polypectomy was projected to have minimal impact on long-term CRC incidence and deaths (not statistically significant). There was a projected decrease of one (4%) major bleeding event and seven (5%) perforation events per year. There was a projected increase of 4800 (1.5%) FIT screens, decrease of 3900 (5.1%) colonoscopies, and a decrease of $3.4 million (1.2%) in total healthcare costs per year, on average. The annual colonoscopies averted and healthcare cost savings increased over time. Results were similar in the alternative scenarios and sensitivity analyses. Returning to FIT screening would have similar clinical outcomes as surveillance colonoscopy but could reduce colonoscopy demand and healthcare costs.

Effect of a FIT-Based Colorectal Cancer Screening Program on Mortality Estimated by the Regression Discontinuity Design.

The fecal immunochemical test (FIT) has been implemented in colorectal cancer (CRC) screening programs, but effect evaluations are lacking. We evaluated the effect of a positive FIT on all-cause and CRC mortality using the regression discontinuity design. The Danish CRC screening program invites all residents 50-74 years old, using a 20-μg hemoglobin/g feces cutoff for colonoscopy referral. In this cohort study, we followed all first-time screening participants from 2014-2019 until 2020. We estimated the local effect of screening results, of just above the cutoff vs. just below, as hazard ratios (HRs) between models fitted at each side of the cutoff. We conducted the analysis within a narrow hemoglobin range (≥17 and <23, n= 16,428) and a wider range (≥14 and <26, n= 35,353). Those screened just above the cutoff had lower all-cause mortality compared with below (HR= 0.87, 95% confidence interval: 0.69; 1.10), estimated from the narrow range. The CRC mortality analysis had few outcomes. In the wider range, those with a FIT just above the cutoff had a lower hazard of CRC mortality compared with just below the cutoff (HR= 0.49, 95% confidence interval: 0.17; 1.41). A FIT result just above the cutoff, leading to referral to colonoscopy, pointed towards reduced all-cause and CRC mortality compared with just below the cutoff.

Risk prediction for advanced neoplasia using longitudinal adherence measures to fecal immunochemical test-based colorectal cancer screening programs

BackgroundPatterns of longitudinal adherence may predict advanced neoplasia (AN) detection in subsequent rounds of colorectal cancer (CRC) screening. However, after more than five rounds, it is important to obtain a simplified measure. The aim was to determine the best simplified measure of longitudinal adherence to predict AN detection in CRC screening. MethodsIndividuals with four invitations from a Dutch Fecal immunochemical testing (FIT-)based pilot study and two Italian FIT-based CRC screening programs were included. We calculated AN detection in the fourth round, stratified by prior adherence. Five simplified measures were compared to full information (permutations) using chi-squared goodness-of-fit: adherence previous invitation, consistency, frequency, frequency + adherence previous invitation, and proportion of invitations covered. ResultsAN detection in the fourth round was highly dependent on prior adherence behavior. For inconsistent adherence, detection in the fourth round was strongly dependent on frequency and time since last participation. The performance of the simplified measures to capture this variation differed considerably. ‘Adherence previous invitation’ scored worst in predicting AN detection. ‘Frequency+adherence previous invitation’ had lowest chi-squared goodness-of-fit. DiscussionThe simplified measure ‘frequency+adherence previous invitation’ is the best measure to reflect patterns of longitudinal adherence and could be used to emphasize to individuals the importance of CRC screening.

Personalized colorectal cancer screening: study protocol of a mixed-methods study on the effectiveness of tailored intervals based on prior f-Hb concentration in a fit-based colorectal cancer screening program (PERFECT-FIT)

BackgroundIn 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 µg 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.MethodsThis 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.DiscussionThe 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.Trial registration: ClinicalTrials.gov, NCT05423886, June 21, 2022, https://clinicaltrials.gov/ct2/show/NCT05423886

The effect of antithrombotic treatment on the fecal immunochemical test for colorectal cancer screening: a nationwide cross-sectional study.

BACKGROUND : Screening for colorectal cancer (CRC) using the fecal immunochemical test (FIT) has been widely adopted. The use of antithrombotic treatment is increasing in the Western world. This study aimed to assess the effects of antithrombotic treatment on the FIT-based Danish national screening program for CRC. METHODS : This was a cross-sectional study of all individuals returning a FIT from 2014 until 2016. The effect of antithrombotic treatment on FIT positivity and the positive predictive value (PPV) were assessed using proportions and multivariable Poisson regression. RESULTS : Of 884 036 invited individuals, we identified 551 570 participants. A positive FIT was observed in 9052 of 77 007 individuals (11.8 %) receiving antithrombotic treatment compared with 28 387 of 474 587 individuals (6.0 %) receiving no treatment. The adjusted relative risk (RR) for a positive FIT was 1.59 (95 %CI 1.56-1.63) for any treatment. Nonvitamin K oral anticoagulants (NOACs) were associated with the largest increase in FIT positivity (adjusted RR 2.40, 95 %CI 2.48-2.54). The proportion of CRC detected at colonoscopy was slightly lower among patients on antithrombotic treatment (6.0 %, 95 %CI 5.5 %-6.6 %) than among treatment-naïve patients (6.4 %, 95 %CI 6.1 %-6.7 %). The PPV for CRC or high risk adenomas was decreased nearly twofold in patients treated with NOAC (adjusted RR 0.58, 95 %CI 0.51-0.66]). CONCLUSION : Antithrombotic treatment was associated with a decreased PPV in FIT-based CRC screening.

Perceived Importance of the Benefits and Harms of Colorectal Cancer Screening: A Best-Worst Scaling Study

ObjectivesTo elicit the relative importance of the benefits and harms of colorectal cancer (CRC) screening among potential screening participants in the Dutch population. MethodsIn a consensus meeting with 11 experts, risk reduction of CRC and CRC deaths (benefits) and complications from colonoscopy, stress of receiving positive fecal immunological test (FIT) results, as well as false-positive and false-negative FIT results (harms) were selected as determinant end points to consider during decision making. We conducted an online best-worst scaling survey among adults aged 55 to 75 years from the Dutch Health Care Consumer Panel of The Netherlands Institute for Health Services Research to elicit preference values for these outcomes. The preference values were estimated using conditional logit regression. ResultsOf 265 participants, 234 (89%) had ever participated in CRC screening. Compared with the stress of receiving a positive FIT result, the outcome perceived most important was the risk of CRC death (odds ratio [OR] 4.5; 95% confidence interval [CI] 3.9-5.1), followed by risk of CRC (OR 4.1; 95% CI 3.6-4.7), a false-negative FIT result (OR 3.1; 95% CI 2.7-3.5), colonoscopy complications (OR 1.6; 95% CI 1.4-1.8), and a false-positive FIT result (OR 1.4; 95% CI 1.3-1.6). The magnitude of these differences in perceived importance varied according to age, educational level, ethnic background, and whether the individual had previously participated in CRC screening. ConclusionDutch men and women eligible for FIT-based CRC screening perceive the benefits of screening to be more important than the harms.

The multitarget fecal immunochemical test versus the fecal immunochemical test for programmatic colorectal cancer screening: a cross-sectional intervention study with paired design

BackgroundMany screening programs for colorectal cancer (CRC) use the fecal immunochemical test (FIT) to triage individuals for colonoscopy. Although these programs reduce CRC incidence and CRC-related mortality, the detection of advanced precursor lesions (advanced adenomas and advanced serrated polyps) by FIT could be improved. As an alternative for FIT, the antibody-based multitargetFIT (mtFIT) has been proposed. The mtFIT measures three protein markers: hemoglobin, calprotectin, and serpin family F member 2. In a retrospective diagnostic accuracy study in a large colonoscopy-controlled series (n = 1284), mtFIT showed increased sensitivity for advanced neoplasia (AN), at equal specificity, compared to FIT (42.9% versus 37.3%; p = 0.025). This increase was mainly due to a higher sensitivity of mtFIT for advanced adenomas (37.8% versus 28.1% for FIT; p = 0.006). The present mtFIT study aims to prospectively validate these findings in the context of the Dutch national CRC screening program.MethodThe mtFIT study is a cross-sectional intervention study with a paired design. Eligible subjects for the Dutch FIT-based national CRC screening program are invited to perform mtFIT in addition to FIT. Samples are collected at home, from the same bowel movement, and are shipped to a central laboratory by postal mail. If either one or both tests are positive, participants are referred for colonoscopy. Detailed colonoscopy and pathology data are centrally stored in a national screening database (ScreenIT; Topicus, Deventer, the Netherlands) that is managed by the screening organization, and will be retrieved for this study. We aim to determine the relative sensitivity for AN, comprising of CRC, advanced adenomas and advanced serrated polyps, of mtFIT compared to FIT at an equal positivity rate. Additionally, we will use the Adenoma and Serrated Pathway to Colorectal CAncer model to predict lifetime health effects and costs for programmatic mtFIT- versus FIT-based screening. The target sample size is 13,131 participants.DiscussionThe outcome of this study will inform on the comparative clinical utility of mtFIT versus FIT in the Dutch national CRC screening program and is an important step forward in the development of a new non-invasive stool test for CRC screening.Trial registrationClinicaltrials.gov; NCT05314309, registered April 6th 2022, first inclusions March 25th 2022 https://clinicaltrials.gov/ct2/results?cond=&term=NCT05314309&cntry=&state=&city=&dist=.

Factors associated with interval colorectal cancer after negative FIT: Results of two screening rounds in the Dutch FIT-based CRC screening program.

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 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 (>40-46.9μg/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 (0-2.6μg/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.

Modelling optimal use of temporarily restricted colonoscopy capacity in a FIT-based CRC screening program: Application during the COVID-19 pandemic.

ObjectiveThe 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.DesignWe 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.ResultsIncreasing 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).ConclusionThis 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.