National Colorectal Cancer Screening Program Research Articles

Screening kolorektálního karcinomu v České republice – minulost, současnost a budoucnost

The National Colorectal Cancer Screening Program has been conducted in the Czech Republic since 2000 and serves as an example of interdisciplinary collaboration. Specialists from gastroenterology, general practice, gynecology, and clinical biochemistry are involved in the program. It is based on two primary methods: the screening fecal immunochemical test for occult bleeding (iFOBT, FIT) and preventive colonoscopy (FOBT-positive colonoscopy and screening colonoscopy). The program‘s effectiveness is evidenced by the high number of detected colorectal precancerous and malignant lesions. Between 2006 and 2023, a total of 531,362 preventive colonoscopies were performed, diagnosing 202,575 patients with adenomas (38.1%) and 14,473 patients with cancers (2.7%). Program quality is monitored by indicators focused on both organization (target population coverage) and screening methods. Coverage with screening tests in a 2-year interval has consistently ranged around 30%, except between 2020 and 2021 during the COVID-19 pandemic (27%), reaching 30.0% in 2023. Non-screening tests also affect epidemiological indicators, with total coverage by all relevant methods in a 2-year interval in 2023 amounting to 37.5%. Colonoscopies are evaluated using six parameters (number of examinations, bowel preparation quality, total colonoscopies, and adenoma detection rate in total, in both women and men). In 2023, 72% of screening colonoscopy centers met all of these indicators. FOBT analyzers now must have the regular external quality assessment (EQA), which should help stabilize test positivity, standing at 9.1% in 2023. Thanks to the National Colorectal Cancer Screening Program, favorable epidemiological trends have been observed, with a 32.3% decrease in incidence and a 47.8% decrease in mortality between 2000 and 2022. The future of the program lies in its further optimization, with a goal of both increasing coverage of the target population by examination and quality improvement, ensuring the program’s feasibility and efficiency. Key words: colorectal cancer – adenoma – screening – colonoscopy – fecal immunochemical test – quality indicators

Association between Endoscopist Volume and Interval Cancers after Colonoscopy: Results from the National Colorectal Cancer Screening Program in Korea.

The rate of interval colorectal cancer (iCRC) is now accepted as a key performance indicator of organized colorectal cancer (CRC) screening programs. We aimed to examine the association between endoscopist volumes and the rate of iCRC among individuals with a positive fecal immunochemical test (FIT) within a nationwide population-based CRC screening program. Individuals aged ≥ 50 years who underwent colonoscopy after a positive FIT from January 1, 2019 until December 31, 2020 in the Korean National Cancer Screening Program (KNCSP) were enrolled. We converted the data into per-endoscopist screening results, calculated the iCRC rates per endoscopist, and compared them to the previous year's annual volume that was divided into five groups (V1, 1-9; V2, 10-29; V3, 30-59; V4, 60-119; V5, ≥ 120). A total of 10,412 endoscopists performed 216,907 colonoscopies. Overall, the average rate of iCRC per endoscopist was 8.46 per 1,000 examinations. Compared with the group with the highest volume (V5 group), the rate of iCRC was 2.21 times higher in the V1 group. Similar trends were observed in the other groups (V2: relative risks [RR], 2.15; 95% confidence interval [CI], 1.57 to 2.94; V3: RR, 1.56; 95% CI, 1.15 to 2.13; V4: RR, 1.18; 95% CI, 0.83 to 1.67). The findings emphasize that endoscopists with lower procedure volumes have higher risks of interval cancer being missed or undetected. To maximize the preventative impact of colonoscopy for CRC, this issue should be addressed by monitoring endoscopist volumes and variations in performances.

Development of an algorithm combining blood-based biomarkers, fecal immunochemical test, and age for population-based colorectal cancer screening

Implementation of screening modalities have reduced the burden of colorectal cancer (CRC), but high false positive rates pose a major problem for colonoscopy capacity. We aimed to create a tailored screening algorithm that expands the fecal immunochemical test (FIT) with a blood specimen and current age to improve selection of individuals for diagnostic colonoscopy. In this prospective multi-center study, eight blood-based biomarkers (CEA, Ferritin, hsCRP, HE4, Cyfra21-1, Hepsin, IL-8 and OPG) were investigated in 1,977 FIT positive individuals from the Danish national CRC screening program undergoing follow-up colonoscopy. Specimens were analyzed on ARCHITECT i2000®, ARCHITECT c8000® or Luminex xMAP® machines. FIT analyses and blood-based biomarker data were combined with clinical data (i.e., age and colonoscopy findings) in a cross-validated logistic regression model (algorithm) benchmarked against a model solely using the FIT result (FIT model) applying different cutoffs for FIT positivity. The cohort included individuals with CRC (n = 240), adenomas (n = 938) or no neoplastic lesions (n = 799). The cross-validated algorithm combining the eight biomarkers, quantitative FIT result and age performed superior to the FIT model in discriminating CRC versus non-CRC individuals (AUC 0.77 versus 0.67, p < 0.001). When discriminating individuals with either CRC or high- or medium-risk adenomas versus low-risk adenomas or clean colorectum, the AUCs were 0.68 versus 0.64 for the algorithm and FIT model, respectively. The algorithm presented here can improve patient allocation to colonoscopy, reducing colonoscopy burden without compromising cancer and adenomas detection rates or vice versa.

Screening, awareness and challenges for colorectal cancer treatment in Saudi Arabia: an update

Colorectal cancer (CRC) is the second most common cancer in the world. In Saudi Arabia, CRC is the most common cancer in males and the third most common in females, and its incidence rate is rising as the country continues to develop. However, the country does not have a national CRC screening program for CRC. This review aims to review recent studies that have attempted to address and rectify this issue and discern the most notable and prevalent barriers. Despite these efforts, guidelines are still lacking. Two prospective studies have been conducted in recent years, one of which was a national pilot screening program conducted by the Ministry of Health (MOH). While both had a similar number of participants, the colonoscopy rate for patients with a positive fecal immunochemical test (FIT) in the MOH program was only 20% compared to 75.8% in the Al-Kharj program. Awareness of the Saudi population regarding CRC and its screening appears to be insufficient. The most common barriers to patients' willingness to undergo screening were embarrassment, fear, and pain. Barriers to physicians are mostly related to factors outside their hands, such as lack of equipment and time. We conclude that efforts should be made to establish a national screening program and improve awareness of the population and physicians.

Abstract 6079: Comparison of FIT and cell-free DNA analyses for detection of individuals with colorectal cancer in population based screening

Abstract Background The fecal immunochemical test (FIT) is widely used in population based colorectal cancer (CRC) screening programs. Recently, circulating cell-free DNA (cfDNA) analyses have emerged as a new avenue for early cancer detection. The performance of cfDNA methods in comparison with FIT is currently unknown. The present study compared pre-operative cfDNA analyses to FIT for detection of patients with CRC who participated in a population-based screening program. Methods In the Dutch national CRC screening program, individuals aged 55-75 years are biennially invited to perform a single FIT. The database of the Dutch CRC screening program was queried to identify individuals with FIT data who also participated in two cfDNA studies, PLCRC-MEDOCC and PLCRC-PROVENC3 (AACR abstract C. Rubio Alarcón). Sensitivities with 95% confidence intervals (CI) for detecting individuals with CRC were determined for FIT, tumor-informed cfDNA analyses, as well as both tests combined. For FIT, sensitivities were determined at 20 µg and 47 µg hemoglobin (Hb)/g feces positivity cut-offs as these represent the most commonly used international and Dutch cut-offs, respectively. Liquid biopsy analyses were performed using next generation sequencing of cfDNA. Tumor-specific alterations were identified through parallel next generation sequence analysis of resected tumor tissues. Results The query identified 120 individuals with stage I (n=3, 2.5%), stage II (n= 57, 47.5%) and stage III (n=60, 50.0%) CRC who had participated in the Dutch CRC screening program and either PLCRC-MEDOCC or PLCRC-PROVENC3. All FIT samples were collected at a median time of 38 days before diagnosis (IQR 27-112 days). FIT sensitivity for detection of individuals with CRC was 83.3% (100/120 CRCs, 95% CI 75.4-89.5%) at a 20 µg Hb/g feces cut-off and 80.0% (96/120, 95% CI 71.7-86.7%) at a 47 µg Hb/g feces cut-off. Tumor-informed cfDNA analyses detected 75.8% (91/120, 95% CI 67.2-83.2%) of individuals with CRC in this population. The combination of cfDNA analyses and and FIT (20 µg Hb/g feces cut-off) identified almost all individuals with CRCs (119/120, sensitivity 99.2%, 95% CI 97.0-100%). The individual who was missed had a cancer that was a T3N0 microsatellite stable moderately differentiated adenocarcinoma in the ascending colon. Discussion While both FIT and cfDNA analyses identified most CRC cases (75-83%) in this series, both tests also demonstrated a substantial level of complementarity, indicating that in principle combining FIT with cell-free DNA testing would allow to increase sensitivity of CRC screening. Since the cell-free DNA tests used here are tumor-informed, which in real life screening practice is not feasible, it remains to be determined to what extent this result can be reached using non-tumor-informed approaches. Citation Format: Pieter Henk Abraham Wisse, Carmen Rubio-Alarcon, Suzanna J. Schraa, Adria C. Mosquera, Mark Sausen, Remond J. Fijneman, Geraldine R. Vink, Meike de Wit, Jillian Phallen, Victor E. Velculescu, Beatriz Carvalho, Gerrit A. Meijer. Comparison of FIT and cell-free DNA analyses for detection of individuals with colorectal cancer in population based screening [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6079.

The prognostic value of tumor budding in a thoroughly characterized stage II colon cancer population in the context of a national screening program

Tumor budding as a prognostic marker in colorectal cancer has not previously been investigated in a cohort of screened stage II colon cancer patients. We assessed the prognostic significance of tumor budding in a thoroughly characterized stage II colon cancer population comprising surgically resected patients in the Region of Southern Denmark from 2014 to 2016. Tumors were re-staged according to the 8th edition of UICC TNM Classification, undergoing detailed histopathological evaluation and tumor budding assessment following guidelines from the International Tumor Budding Consensus Conference. Prognostic evaluation utilized Kaplan-Meier curves, log-rank tests, and Cox proportional hazard models for time to recurrence (TTR), recurrence-free survival (RFS), and overall survival (OS).Out of 497 patients, 20% were diagnosed through the national colorectal cancer screening program. High-grade tumor budding (Bd3) was found in 19% of tumors and was associated with glandular subtype, perineural invasion, mismatch repair proficient tumors, and tumor recurrence (p < 0.001, p < 0.001, p = 0.045, and p = 0.007 respectively). In multivariable Cox regression, high-grade budding was a significant prognostic factor for TTR compared to low-grade (Bd3 HR 2.617; p = 0.007). An association between tumor budding groups and RFS was observed, and the difference was significant in univariable analysis for high-grade compared to low-grade tumor budding (Bd3 HR 1.461; p = 0.041). No significant differences were observed between tumor budding groups and OS.High-grade tumor budding is a predictor of recurrence in a screened population of patients with stage II colon cancer and should be considered a high-risk factor in a shared decision-making process when stratifying patients to adjuvant chemotherapy.

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.

Differences between men and women with respect to colorectal cancer mortality despite screening colonoscopy

Background and study aimsWomen aged 55 to 59 years have a similar prevalence rate and number needed to screen for colorectal adenomas as men at a ten years younger age.The aim of this study was to determine sex specific differences in colorectal cancer mortality and estimate the association with adenomas at screening colonoscopy. MethodsThis retrospective study analyzed 323,139 individuals who underwent colonoscopy within a national colorectal cancer screening program in Austria between 01/2007 and 12/2020. ResultsMedian age was (60 years [IQR 54-67]) and sex distribution in all age groups was nearly identical. Men had significantly higher odds to have an adenoma or serrated polyp, low risk polyps, high-risk polyps, or colorectal cancer detected at colonoscopy than women (OR 1.83 [1.80-1.86], OR 1.46 [1.44-1.49], OR 1.74 [1.69-1.80], and OR 1.87 [1.70-2.05] respectively). Strikingly, male sex, when compared to female sex, was associated with an almost 2-fold (HR 1.67 [1.05-2.67]) increased risk to die from colorectal cancer when an adenoma or serrated polyp, and a 4-fold (HR 4.14 [2.72-6.3]) increased risk when a high-risk polyp was found at the screening colonoscopy. The cumulative incidence for death of colorectal cancer for 60-year-old individuals was 8.5-fold higher in men as compared to women. Markedly, this gender gap narrowed with increasing age while the difference in deaths of other causes remained similar in all age groups. ConclusionOur findings strengthen the necessity of sex specific screening recommendations.Importantly, further prospective studies should focus on sex difference in tumor biology to propose personalized surveillance guidelines.

Evaluation of the effectiveness of colorectal cancer screening intervention.

The effectiveness of the Colorectal Cancer (CRC) screening program is assessed based on the reduction in CRC mortality and incidence rates over time. To accurately estimate the long-term impact, it is advisable to monitor additional indicators such as age and stage-specific incidence rates. Our objective is to evaluate the effectiveness of the National CRC Screening Program in Turkey and analyze its influence on disease stage at diagnosis and survival rates. The National CRC Screening Program was considered an intervention and the distribution of local, regional, and distant diseases, and survival estimates were assessed before and after the intervention to evaluate the effectiveness of the intervention. 518 patients were included in the study. At the time of diagnosis, localized, regional, and distant disease in pre-intervention were 31.3%, 42.9%, 25.8%, while post-intervention were 42.8%, 33.3%, 23.9%, respectively (p = 0.020). The relative effectiveness of the intervention in males, females, and 50-70 ages were calculated as 1.2[95% CI 0.95-1.73], 1.5[95% CI 1.04-2.18], and 1.6[95% CI 1.21-2.28] in localized disease, 0.8[95% CI 0.67-1.18], 0.6[95% CI 0.43-0.90], and 0.6[95% CI 0.46-0.81] in regional diseases, 0.8[95% CI 0.57-1.20], 1.1[95% CI 0.66-1.84], and 1.0[95% CI 0.70-1.57] in distant disease, respectively. A noticeable shift in the disease stage at the time of diagnosis was observed; however, this shift varied among gender and age groups. To effectively evaluate the impact of a cancer screening program on reducing the incidence and mortality rates of the disease, it is essential to monitor and analyze these indicators alongside 5-10-year survival estimates and stage changes at the time of diagnosis.

The Effectiveness of the National Colorectal Cancer Screening Program in Korea

The Effectiveness of the National Colorectal Cancer Screening Program in Korea

Temporal trends in age- and stage-specific incidence of colorectal adenocarcinomas in Germany

BackgroundA national colorectal cancer (CRC) screening programme was launched in 2002 in Germany. A comprehensive evaluation of the programme effectiveness using real-world data is still lacking. In addition, there are regional reports on increasing colorectal cancer incidence in younger populations. Therefore, we aimed to describe and compare the overall, age- and stage-specific incidence trends for colorectal, colon and rectal cancer.MethodsWe used data from seven population-based cancer registries in Germany. We report absolute and relative changes in incidence rates between the early screening phase (2003–2005) and the most recent time period available (2015–2017), as well as annual percent changes. We analysed incidences according to tumour site (colorectum, colon, and rectum) and to six age groups (young adults: 15–34, 35–39, 40–49, screening-entitled/older adults: 50–54, 55–69 and 70 + years old).ResultsIn our sample of 271,011 colorectal adenocarcinomas, about two-thirds were located in the colon and 95% of them occurred in the age group 50+ (50–54: 5%, 55–69: 32.8%, 70+: 57.2%). For the time period 2003–2005 the age-specific incidence rates of individuals in the age group 55–69 were about 76/100,00 for colon and 54/100,000 for rectal cancer (age group 70 + colon: 179/100,000; rectum: 84/100,000). The incidence rates in young adults were less than 13% of that of individuals in the age group 55–69 (< 5% of individuals aged 70+; <33% of individuals aged 50–54).Over time, incidence decreased in individuals at the age of 55+, for all subsites considered as well as for early and late stage cancers (with few exceptions), while incidence of young adult CRC (both early and late stage) increased steepest in the youngest age groups. For late stage rectal cancer, a shift was observed in all age groups from UICC stage IV to stage III being the most frequent stage.ConclusionsSix years after the introduction of the national colonoscopy screening program, late stage CRC incidence began to decline substantially in the screening-eligible age groups (55-69, 70+). It is likely that this decline and the increase in early stage CRC observed in younger age groups can be attributed to the program. Long lasting public awareness campaigns for CRC screening might have led to opportunistic screening in younger adults. Whether these benefits outweigh the possible harm of screening in younger age groups remains unclear.

Výsledky z evaluace screeningu kolorektálního karcinomu v České republice

Introduction: Colorectal cancer screening, which was introduced in the Czech Republic in 2000, plays an important role in reducing the population burden. It is necessary to continuously evaluate the organised population-based program and introduce necessary adjustments to ensure its high effectiveness, which in the long term leads to a reduction in the incidence and mortality of the disease. The aim of this article is to summarise and discuss the key results of the evaluation of the National Colorectal Cancer Screening Program based on available national data. Material and methods: The evaluation used the registries of the National Health Information System, the Registry of Preventive Colonoscopies, and data on population demographics managed by the Czech Statistical Office. The analysis was carried out on available data up to 2021. Basic indicators were calculated in accordance with international recommendations, which were adapted for the Czech environment. Results: A number of performance indicators for colorectal screening demonstrate the negative impact of the COVID-19 pandemic in 2020 and 2021. Coverage of the target population by screening has stabilised at around 30% before the pandemic. Considering a three-year interval, the full coverage of the target population by screening reaches around 50%. Participation rates for follow-up colonoscopy after a positive faecal occult blood test (FOBT) screening ranged between 60 and 70% over time. FOBT screening positivity increased in the recent years up to 10%, which is reflected in the increase in the average waiting time for follow-up FOBT+ colonoscopy. Despite the identified limitations of the screening program, there has been a clear long-term decline in colorectal cancer incidence and mortality. Conclusion: The comprehensive screening information system enables the evaluation of colorectal screening. The evaluated indicators show that despite the positive impact of the screening program on the population burden, it still has its opportunities for improvement, and therefore it is essential to continue its monitoring in order to improve the quality of the whole program. Keywords colonoscopy, colorectal neoplasms, mass screening, occult blood, program evaluation, performance indicators, registries

Liquid Biopsies for Colorectal Cancer and Advanced Adenoma Screening and Surveillance: What to Measure?

Colorectal cancer (CRC) colonoscopic surveillance is effective but burdensome. Circulating tumor DNA (ctDNA) analysis has emerged as a promising, minimally invasive tool for disease detection and management. Here, we assessed which ctDNA assay might be most suitable for a ctDNA-based CRC screening/surveillance blood test. In this prospective, proof-of-concept study, patients with colonoscopies for Lynch surveillance or the National Colorectal Cancer screening program were included between 7 July 2019 and 3 June 2022. Blood was drawn, and if advanced neoplasia (adenoma with villous component, high-grade dysplasia, ≥10 mm, or CRC) was detected, it was analyzed for chromosomal copy number variations, single nucleotide variants, and genome-wide methylation (MeD-seq). Outcomes were compared with corresponding patients' tissues and the MeD-seq results of healthy blood donors. Two Lynch carriers and eight screening program patients were included: five with CRC and five with advanced adenomas. cfDNA showed copy number variations and single nucleotide variants in one patient with CRC and liver metastases. Eight patients analyzed with MeD-seq showed clustering of Lynch-associated and sporadic microsatellite instable lesions separate from microsatellite stable lesions, as did healthy blood donors. In conclusion, whereas copy number changes and single nucleotide variants were only detected in one patient, cfDNA methylation profiles could discriminate all microsatellite instable advanced neoplasia, rendering this tool particularly promising for LS surveillance. Larger studies are warranted to validate these findings.

Less Invasive Primary Treatment for Colorectal Cancer After Implementation of National Screening: A Nationwide Cohort Study.

The effect of organized colorectal cancer (CRC) screening on type of primary treatment remains sparsely investigated. This study evaluated the difference in primary treatment strategy between patients diagnosed with screen-detected (SD-CRC) and non-screen-detected colorectal cancer (NSD-CRC) in a national CRC screening program. This was a retrospective national register-based cohort study. Data on patients aged between 50 and 75years and diagnosed with SD-CRC or NSD-CRC were retrieved from the national colorectal cancer screening database and the Danish Colorectal Cancer Group database. Outcomes related to surgical invasiveness were compared between the two cohorts. Differences were expressed as relative risks using log-binomial generalized linear regression models. UICC stage IV specific outcomes were analyzed using the same method. All analyses were adjusted for sex, age, type of cancer (colonic/rectal), and Charlson comorbidity index. The study included 4707 patients with SD-CRC and 7328 with NSD-CRC. Therapeutic flexible endoscopy (SD-CRC: n = 636 vs. NSD-CRC: n = 334, RR: 2.50, P < 0.001), (robotic-assisted) laparoscopic resection ((n = 616 vs. n = 773, RR: 1.27, P < 0.001), n = 2759 vs. n = 3471, RR: 1.11, P < 0.001), and radical resection (n = 3890 vs. n = 4834, RR: 1.02, P = 0.002) were significantly more frequent in the SD-CRC group. The rates of emergency priority (n = 32 vs. n = 562, RR: 0.09, P < 0.001), open surgery (n = 391 vs. n = 1410, RR: 0.53, P < 0.001), supplementary organ resection (n = 259 vs. n = 860, RR: 0.56, P < 0.001), and stoma formation (n = 526 vs. n = 1040, RR: 0.89, P = 0.007) were significantly lower in the SD-CRC group. The rate of patients undergoing surgery with UICC stage IV disease was significantly higher in the SD-CRC group (SD-CRC: n = 262, NSD-CRC: n = 994, RR: 1.43, P < 0.001). SD-CRC remained associated with less invasive primary surgical treatment following adjustment for potential healthy user bias. UICC stage IV disease may be less advanced in patients with SD-CRC.

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

Optimizing Screening for Colorectal Cancer: An Algorithm Combining Fecal Immunochemical Test, Blood-Based Cancer-Associated Proteins and Demographics to Reduce Colonoscopy Burden

BackgroundFecal Immunochemical Test (FIT) is widely used in population-based screening for colorectal cancer (CRC). This had led to major challenges regarding colonoscopy capacity. Methods to maintain high sensitivity without compromising the colonoscopy capacity are needed. This study investigates an algorithm that combines FIT result, blood-based biomarkers associated with CRC, and individual demographics, to triage subjects sent for colonoscopy among a FIT positive (FIT+) screening population and thereby reduce the colonoscopy burden. Materials and methodsFrom the Danish National Colorectal Cancer Screening Program, 4048 FIT+ (≥100 ng/mL Hemoglobin) subjects were included and analyzed for a panel of 9 cancer-associated biomarkers using the ARCHITECT i2000. Two algorithms were developed: 1) a predefined algorithm based on clinically available biomarkers: FIT, age, CEA, hsCRP and Ferritin; and 2) an exploratory algorithm adding additional biomarkers: TIMP-1, Pepsinogen-2, HE4, CyFra21-1, Galectin-3, B2M and sex to the predefined algorithm. The diagnostic performances for discriminating subjects with or without CRC in the 2 models were benchmarked against the FIT alone using logistic regression modeling. ResultsThe discrimination of CRC showed an area under the curve (AUC) of 73.7 (70.5-76.9) for the predefined model, 75.3 (72.1-78.4) for the exploratory model, and 68.9 (65.5-72.2) for FIT alone. Both models performed significantly better (P < .001) than the FIT model. The models were benchmarked vs. FIT at cutoffs of 100, 200, 300, 400, and 500 ng/mL Hemoglobin using corresponding numbers of true positives and false positives. All performance metrics were improved at all cutoffs. ConclusionA screening algorithm including a combination of FIT result, blood-based biomarkers and demographics outperforms FIT in discriminating subjects with or without CRC in a screening population with FIT results above 100 ng/mL Hemoglobin.

Subsequent participation in organized FIT based screening following screen-derived colonoscopy – A Danish nationwide cohort study

IntroductionIn the Danish National Colorectal Cancer (CRC) screening program, participants with screen-detected low-risk adenomas are invited to a new faecal immunochemical test (FIT) screening after two years. However, participation rate in next FIT screening is unknown. We aimed to investigate this subsequent participation rate within the Danish CRC screening program. MethodsThis nationwide register-based study included participants aged 50–72 years registered with FIT screening in the Danish CRC screening program between January 1, 2016, and June 30, 2017. Participants were included if their index FIT was negative or if it was positive and the subsequent colonoscopy detected low-risk adenomas. Invitees were categorized as subsequent participants if they returned a FIT within 135 days following the invitation to screening. We estimated the relative risk for participation depending on screening outcome, age, and sex. Result415,107 with a negative result and 5,550 with low-risk adenomas were included. 86.0% (85.9;86.1) of the invitees with a negative result participated in the subsequent screening, while 71.8% (70.6;73.0) of the invitees with low-risk adenomas participated subsequently. The risk of participation in the subsequent screening was significantly lower among all age groups of men and women with low-risk adenomas compared to similar groups with negative results. ConclusionInvitees with low-risk adenomas detected at their initial colonoscopy are less likely to participate in the subsequent screening than invitees with negative results. This association was found in all age groups and for both sexes. Further studies are necessary to assess whether non-attendance is more pronounced in specific subgroups.

Screening or symptoms? Colorectal cancer diagnosis in Uruguay.

71 Background: Colorectal cancer (CRC) remains a major health burden worldwide. Screening is employed due to its proven efficacy in reducing CRC incidence and mortality. In Uruguay, there is a longstanding National CRC screening program using fecal occult blood test (FOBT) as the preferred method. It is to be expected that patients with screen-detected CRC have better prognosis than those with symptoms due to earlier diagnosis and other favorable tumor/host characteristics. Beyond the well described earlier stage at diagnosis, other aspects have not been widely studied and data is sparse. An increasing proportion of CRC patients are diagnosed by screening rather than symptoms. Aim: We sought to establish and evaluate the correlation between clinicopathological features and TNM stage at diagnosis and diagnostic modality. Methods: A retrospective review of all newly diagnosed CRC patients from January 2008 to December 2021 was conducted by the authors. A total of 934 patients aged 50-80 years at diagnosis were included. Clinical, histological, diagnostic and treatment data was collected and findings were stratified and correlated according to screening detection vs symptomatic patients. Results: On one hand, 15% of patients had a positive FOBT leading up to their diagnosis. FOBT detected tumors presented a less advanced locoregional T-N staging (p = 0.001). Tumors were preferentially located in the proximal colon (33.1 vs 19.9%); p&lt;0.001. Stage I CRC was more frequently detected in subjects with positive FOBT (14.2%) than in individuals with symptoms (5.9%); p = 0.002. Conversely, detection rates for stage IV CRC were 17.7% and 26.7% respectively; p = 0.002. A higher percentage of stage III screened patients underwent adjuvant chemotherapy when compared to their symptomatic counterparts (97.7 vs. 85.0 %, p = 0.016). On the other hand, 793 patients (85 %) were diagnosed after onset of signs or symptoms. There was a preponderance of advanced-stage disease (stages III–IV 36-27% respectively). The most common symptoms reported were change in bowel habits (52%), abdominal pain (47 %) and bleeding (45%). The most common overall sign was anemia. One hundred eighty-two patients (22.5%) required an emergency surgery mainly for obstructive colon cancer. Conclusions: Despite equal access to colorectal cancer screening, in Uruguay diagnosis after development of symptomatic cancer remains more common. FOBT detected cancers presented less advanced clinicopathological characteristics and differing management that potentially could be driving a more favorable outcome. Mode of detection is therefore an important indicator that should be taken into account when defining risk assessment in treatment decisions. These findings also support the need for continued improvement and recruitment of patients into screening programs. It must be the focus for future initiatives.

The impact of diabetes on cancer detection during the prevalence round of a national screening program for colorectal cancer.

Diabetes is associated with a higher risk of colorectal cancer (CRC) and inferior survival after CRC. Screening may enable the early detection of CRC. We aimed to assess the impact of diabetes on cancer detection and disease stage during the prevalence round of a national CRC screening program. We performed a register-based cohort study based on the randomized procedure for inviting Danish residents aged 50-74 years to the prevalence round of national CRC screening program in 2014-2017. By comparing the random half of the population who had been invited by 1 May 2016 with the not yet invited half, the effect of screening was assessed by the detection of CRC and disease stage among individuals with and without diabetes. Further, the impact of diabetes on the screening participation rate was calculated. By randomisation, 504,673 individuals had been invited to the CRC screening by 1 May 2016, and 549,359 individuals had not yet been invited. The diabetes prevalence was 10% in both groups. When comparing those not yet invited to those invited, the effect of screening on the number of detected cancers per 100,000 individuals was higher in those with diabetes (from 207 to 494 cancers) than in those without diabetes (from 147 to 364 cancers), and screening resulted in overall higher proportions of stage I cancer. Among those invited to screening, the participation rate was 9.1% lower (95% CI: 8.7%-9.5%) in individuals with versus without diabetes. Despite a lower participation rate, the effect of CRC screening was higher in individuals with diabetes.

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.