A randomised comparison of two faecal immunochemical tests in population-based colorectal cancer screening.

OBJECTIVE: Colorectal cancer screening programmes are implemented worldwide; many are based on faecal immunochemical testing (FIT). The aim of this study was to evaluate two frequently used FITs on participation, usability, positivity rate and diagnostic yield in population-based FIT screening. DESIGN: Comparison of two FITs was performed in a fourth round population-based FIT-screening cohort. Randomly selected individuals aged 50-74 were invited for FIT screening and were randomly allocated to receive an OC -Sensor (Eiken, Japan) or faecal occult blood (FOB)-Gold (Sentinel, Italy) test (March-December 2014). A cut-off of 10 µg haemoglobin (Hb)/g faeces (ie, 50 ng Hb/mL buffer for OC-Sensor and 59 ng Hb for FOB-Gold) was used for both FITs. RESULTS: In total, 19 291 eligible invitees were included (median age 61, IQR 57-67; 48% males): 9669 invitees received OC-Sensor and 9622 FOB-Gold; both tests were returned by 63% of invitees (p=0.96). Tests were non-analysable in 0.7% of participants using OC-Sensor vs 2.0% using FOB-Gold (p<0.001). Positivity rate was 7.9% for OC-Sensor, and 6.5% for FOB-Gold (p=0.002). There was no significant difference in diagnostic yield of advanced neoplasia (1.4% for OC-Sensor vs 1.2% for FOB-Gold; p=0.15) or positive predictive value (PPV; 31% vs 32%; p=0.80). When comparing both tests at the same positivity rate instead of cut-off, they yielded similar PPV and detection rates. CONCLUSIONS: The OC-Sensor and FOB-Gold were equally acceptable to a screening population. However, FOB-Gold was prone to more non-analysable tests. Comparison between FIT brands is usually done at the same Hb stool concentration. Our findings imply that for a fair comparison on diagnostic yield between FIT's positivity rate rather than Hb concentration should be used. TRIAL REGISTRATION NUMBER: NTR5385; Results.

Evaluation of the colorectal cancer screening Programme in the Basque Country (Spain) and its effectiveness based on the Miscan-colon model.

The population-based Basque Colorectal Cancer (CRC) Screening Programme started in 2009 with a biennial immunochemical quantitative test (FIT) biennial and colonoscopy under sedation in positive cases. The population target of 586,700 residents was from 50 to 69 years old and the total coverage was reached at the beginning of 2014. The aim of our study was to determine possible scenarios in terms of incidence, mortality and reduction of Life-years-Lost (L-y-L) in the medium and long term of CRC. METHODS: Invitations were sent out by the Programme from 2009 to 2014, with combined organizational strategies. Simulation was done by MISCAN-colon (Microsimulation Screening Analysis) over 30 years comparing the results of screening vs no-screening, taking the population-based Cancer Registry into account. Lifetime population and real data from the Programme were used from 2008 to 2012. The model was run differentially for men and women. RESULTS: 924,416 invitations were sent out from 2009 to 2014. The average participation rate was 68.4%, CRC detection rate was 3.4% and the Advanced Adenoma detection rate was 24.0‰, with differences observed in sex and age. Future scenarios showed a higher decrease of incidence (17.2% vs 14.7%), mortality (28.1% vs 22.4%) and L-y-L (22.6% vs 18.4%) in men than women in 2030. CONCLUSIONS: The Basque Country CRC Programme results are aligned to its strategy and comparable to other programmes. MISCAN model was found to be a useful tool to predict the benefits of the programme in the future. The effectiveness of the Programme has not been formally established as case control studies are required to determine long term benefits from the screening strategy.

Comparing trends in esophageal adenocarcinoma incidence and lifestyle factors between the United States, Spain, and the Netherlands.

OBJECTIVES: The incidence of esophageal adenocarcinoma (EAC) in the western world has been rapidly increasing. The trends in obesity and other lifestyle-associated factors have been hypothesized to be important drivers of this increase. We tested this hypothesis by comparing changes in these factors with changes in EAC incidence over time between three western countries. METHODS: Data on EAC incidence trends were abstracted from the SEER-9 registry (1975-2009) for the United States, from multiple cancer registries (1980-2004) in Spain, and from Eindhoven Cancer Registry in the Netherlands (1974-2010). In addition, we collected trend data on obesity, smoking, and alcohol consumption. The trend data were analyzed using log-linear regression. RESULTS: In 1980, the EAC incidence was similar among the three countries ((0.46-0.63) per 100,000). EAC incidence increased in all, with the largest increase observed in the Netherlands, followed by the United States and Spain (estimated annual percentage of change=9.7%, 7.4%, 4.3%, respectively). However, this pattern was not observed in lifestyle factors associated with EAC. With regards to obesity, the United States clearly has had the highest prevalence rates both in the past and in the present. For alcohol, the highest consumption rates are seen in Spain. Smoking showed a reverse trend compared with EAC among all three countries in the last 20 years. CONCLUSIONS: International trends in EAC incidence do not match corresponding trends in lifestyle-associated factors including obesity. Our findings suggest that factors other than obesity must be the important drivers for the increase in EAC incidence.

European guidelines for quality assurance in colorectal cancer screening and diagnosis: overview and introduction to the full supplement publication.

Population-based screening for early detection and treatment of colorectal cancer (CRC) and precursor lesions, using evidence-based methods, can be effective in populations with a significant burden of the disease provided the services are of high quality. Multidisciplinary, evidence-based guidelines for quality assurance in CRC screening and diagnosis have been developed by experts in a project co-financed by the European Union. The 450-page guidelines were published in book format by the European Commission in 2010.  They include 10 chapters and over 250 recommendations, individually graded according to the strength of the recommendation and the supporting evidence. Adoption of the recommendations can improve and maintain the quality and effectiveness of an entire screening process, including identification and invitation of the target population, diagnosis and management of the disease and appropriate surveillance in people with detected lesions. To make the principles, recommendations and standards in the guidelines known to a wider professional and scientific community and to facilitate their use in the scientific literature, the original content is presented in journal format in an open-access Supplement of Endoscopy. The editors have prepared the present overview to inform readers of the comprehensive scope and content of the guidelines.

Colorectal cancer risk after removal of polyps in fecal immunochemical test based screening.

Background: Colonoscopy surveillance intervals are based on the predicted risk of metachronous colorectal cancer (CRC) after polyp removal. However, risk estimation per polyp subtype is difficult due to the fact that many patients have multiple polyps. To enable risk estimation per polyp subtypes we examined the metachronous CRC risk of subgroups based on presence or absence of co-occurring findings. Methods: Using high-quality screening colonoscopies performed after a positive fecal immunochemical test between 2014 and 2020 within the Dutch CRC screening program, we applied Cox regression analysis to evaluate the association between findings at baseline colonoscopy and metachronous CRCs. For our primary outcome, we appointed each patient to unique subgroups based on removed polyp subtypes that were present or absent at baseline colonoscopy and used the groups without polyps as reference. High-risk subgroups were individuals with high-risk serrated polyps, defined as serrated polyp ≥10 mm, sessile serrated lesions with dysplasia, or traditional serrated adenomas, as well as high-risk adenomas, defined as adenoma ≥10 mm or containing high-grade dysplasia. Findings: In total 253,833 colonoscopies were included. Over a median follow-up of 36 months (IQR, 21-57), we identified 504 metachronous CRCs. Hazard ratios for metachronous CRC was 1.70 (95% CI, 1.07-2.69) for individuals with high-risk serrated polyps without high-risk adenomas, 1.22 (0.96-1.55) for individuals with high-risk adenomas without high-risk serrated polyps, and 2.00 (1.19-3.39) for individuals with high-risk serrated polyps and high-risk adenomas, compared to patients without polyps. Interpretation: Accounting for co-occurring findings, we observed an increased metachronous CRC risk for individuals that had high-risk serrated polyps with the presence of high-risk adenomas, or individuals with high-risk serrated polyps without high-risk adenomas. These findings could provide more evidence to support post-polypectomy surveillance guidelines. Funding: None.

European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition--Introduction.

Multidisciplinary, evidence-based guidelines for quality assurance in colorectal cancer screening and diagnosis have been developed by experts in a project coordinated by the International Agency for Research on Cancer. The full guideline document covers the entire process of population-based screening. It consists of 10 chapters and over 250 recommendations, graded according to the strength of the recommendation and the supporting evidence. The 450-page guidelines and the extensive evidence base have been published by the European Commission. The first chapter deals with the evidence for the effectiveness of CRC screening; key operational parameters such as age-range, interval between two negative screening examinations, and some combinations of tests; and cost-effectiveness. The content of the chapter is presented here to promote international discussion and collaboration by making the principles and standards recommended in the new EU Guidelines known to a wider professional and scientific community. Following these recommendations has the potential to enhance the control of colorectal cancer through improvement in the quality and effectiveness of the screening process, including multi-disciplinary diagnosis and management of the disease.

Socio-economic inequality of utilization of cancer testing in Europe: A cross-sectional study.

There are currently screening programmes for breast, cervical and colorectal cancer in many European countries. However, the uptake of cancer screening in general may vary within and between countries. The aim of this study is to assess the inequalities in testing utilization by socio-economic status and whether the amount of inequality varies across European regions. We conducted an analysis based on cross-sectional data from the second wave of the European Health Interview Survey from 2013 to 2015. We analysed the use of breast, cervical, and colorectal cancer testing by socio-economic position (household income, educational level and employment status), socio-demographic factors, self-perceived health and smoking behaviour, by using multinomial logistic models, and inequality measurement based on the Slope index of inequality (SII) and Relative index of inequality (RII). The results show that the utilization of mammography (Odds Ratio (OR) = 0.55, 95% confidence interval (95%CI):0.50-0.61), cervical smear tests (OR = 0.60, 95%CI:0.56-0.65) and colorectal testing (OR = 0.82, 95%CI:0.78-0.86) was overall less likely among individuals within a low household income compared to a high household income. Also, individuals with a non-EU country of birth, low educational level and being unemployed (or retired) were overall less likely to be tested. The income-based inequality in breast (SII = 0.191;RII = 1.260) and colorectal testing utilization (SII = 0.161;RII = 1.487) was the greatest in Southern Europe. For cervical smears, this inequality was greatest in Eastern Europe (SII = 0.122;RII = 1.195). We concluded that there is considerable inequality in the use of cancer tests in Europe, with inequalities associated with household income, educational level, employment status, and country of birth.

[National population screening for colorectal carcinoma in the Netherlands: results of the first years since the implementation in 2014]. / Landelijk bevolkingsonderzoek naar colorectaal carcinoom.

OBJECTIVE: To describe the effect of population screening for colorectal carcinoma (CRC) with the faecal immunochemical test, introduced in 2014, on the incidence of CRC in the Netherlands and to analyse differences between patient and tumour characteristics, stage distribution and treatment of carcinomas that were screening-detected and were not detected by screening (non-screening-detected). DESIGN: Retrospective observational study. METHOD: We analysed data from the Netherlands Cancer Registry. We selected all CRCs diagnosed in the 2010-2016 period and calculated incidence rates standardised for the European population. For comparison between screening-detected and non-screening-detected carcinomas, we selected all CRCs diagnosed in 2015. RESULTS: The number of newly diagnosed CRCs rose from 13,028 in 2013 to 15,185 in 2014 and to 15,807 in 2015. This increase could only be seen for the birth years of people who had been invited for population screening during that particular year. The percentage of men was higher for screening-detected carcinomas than for non-screening-detected carcinomas (62% vs 55%). Screening-detected carcinomas were also more often in the left side of the colon (76% vs 64%). The percentage of patients with stage I CRC was higher in the group with screening-detected carcinomas (48% vs 16%). Patients with screening-detected carcinomas more often underwent local treatment or only resection without adjuvant or neoadjuvant treatment than the patients with non-screening-detected carcinomas. CONCLUSION: During the first years after the introduction of population screening, the incidence of CRC has increased as the result of earlier detection. Screening-detected carcinomas have a more favourable stage distribution and these patients are undergoing less-invasive treatment more often.