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Background. Validated microsimulation models have been shown to be useful tools in providing support for colorec- tal cancer (CRC) screening decisions. Aiming to assist European co

Objectives: To quantify the impact of mammography-based screening on the quality of life, disability-adjusted life years (DALYs) averted or quality-adjusted life years (QALYs) gained can be used. We aimed to assess whether the use of DALYs averted or QALYs gained will lead to different cost-effective screening strategies. Methods: Using the microsimulation model MISCAN, we simulated different breast cancer screening strategies varying in starting age (starting at 45, 47, and 50 years), stopping age (stopping at 69, 72, and 74 years), and frequency (annual [A], biennial [B], combination of both [A + B], and triennial [T]). In total, we defined 24 different breast cancer screening strategies, including no screening as a reference strategy. We calculated incremental cost-effectiveness ratios (ICERs) and compared which strategies were on the efficiency frontiers for DALYs and QALYs. Results: Breast cancer screening averted between 46.00 and 105.58 DALYs and gained between 28.69 and 64.50 QALYs per 1000 women. For DALYs there were 5 strategies on the efficiency frontier (T50-69, T50-74, T45-74, B45-74, and A45-74). The same strategies plus one (B45-72) were on the efficiency frontier for QALYs. Conclusions: Using DALYs averted instead of QALYs gained to assess the effects on quality of life from breast cancer screening in the Dutch population yields differences in ICERs, but almost the same strategies were on the efficiency frontiers. Whether the choice in outcome measure leads to a difference in optimal policy depends on the cost-effectiveness threshold.

Background. Validated microsimulation models have been shown to be useful tools in providing support for colorectal cancer (CRC) screening decisions. Aiming to assist European countries in reducing CRC mortality, we developed and validated three regional models for evaluating CRC screening in Europe. Methods. Microsimulation Screening Analysis–Colon (MISCAN-Colon) model versions for Italy, Slovenia, and Finland were quantified using data from different national institutions. These models were validated against the best available evidence for the effectiveness of screening from their region (when available): the Screening for COlon REctum (SCORE) trial and the Florentine fecal immunochemical test (FIT) screening study for Italy; the Norwegian Colorectal Cancer Prevention (NORCCAP) trial and the guaiac fecal occult blood test (gFOBT) Finnish population-based study for Finland. When published evidence was not available (Slovenia), the model was validated using cancer registry data. Results. Our three models reproduced age-specific CRC incidence rates and stage distributions in the prescreening period. Moreover, the Italian and Finnish models replicated CRC mortality reductions (reasonably) well against the best available evidence. CRC mortality reductions were predicted slightly larger than those observed (except for the Florentine FIT study), but consistently within the corresponding 95% confidence intervals. Conclusions. Our findings corroborate the MISCAN-Colon reliability in supporting decision making on CRC screening. Furthermore, our study provides the model structure for an additional tool (EU-TOPIA CRC evaluation tool: http://miscan.eu-topia.org) that aims to help policymakers and researchers monitoring or improving CRC screening in Europe.

Background: Organised cervical cancer (CC) screening programmes are delivered in many different ways across the European Union and its regions. Our aim was to systematically review the impact of these programs on CC mortality. Methods: Two independent reviewers identified all eligible studies investigating the effect of organised screening on CC mortality in Europe. Six databases including Embase, Medline and Web of Science were searched (March 2018) with predefined inclusion and exclusion criteria. Only original studies with at least five years of follow-up were considered. Validated tools

Background: The aim of this study was to quantify the impact of organised mammography screening on breast cancer mortality across European regions. Therefore, a systematic review was performed including different types of studies from all European regions and stringently used clearly defined quality appraisal to summarise the best evidence. Methods: Six databases were searched including Embase, Medline and Web of Science from inception to March 2018. To identify all eligible studies which assessed the effect of organised screening on breast cancer mortality, two reviewers independently applied predefined inclusion and exclusion criteria. Original studies in English with a minimum follow-up of five years that were randomised controlled trials (RCTs) or observational studies were included. The Cochrane risk of bias instrument and the Newcastle–Ottawa Scale were used to assess the risk of bias. Results: Of the 5015 references initially retrieved, 60 were included in the final analysis. Those comprised 3

Background: Populations differ with respect to their cancer risk and screening preferences, which may influence the performance of colorectal cancer (CRC) screening programs. This review aims to systematically compare the mortality effect of CRC screening across European regions. Methods: Six databases including Embase, Medline, Web of Science, PubMed publisher, Google Scholar and Cochrane Library were searched for relevant studies published before March 2018. Bibliographic searches were conducted to select studies assessing the effect of various screening tests (guaiac fecal occult blood test [gFOBT]; flexible sigmoidoscopy [FS]; fecal immunochemical test [FIT] and colonoscopy) on CRC mortality in Europe (PROSPERO protocol: CRD42016042433). Abstract reviewing, data extraction and risk of bias assessment were conducted independently by two reviewers. Results: A total of 18 studies were included; of which, 11 were related to gFOBT, 4 to FS, 2 to FIT and 1 to colonoscopy; 8 were randomised clinical trials, and 10, observational studies, and an approximately equal number of studies represented Northern, Western and Southern European regions. Among individuals invited to screening, CRC mortality reductions varied from 8% to 16% for gFOBT and from 21% to 30% for FS. When studies with a high risk of bias were considered, ranges were more extensive. The estimated effectiveness of gFOBT and FS screening appeared similar across different European regions. Conclusions: CRC mortality impact of inviting individuals with similar adopted screening strategies (gFOBT or FS) may be consistent across several European settings.

The benefits of population-based screening for breast cancer are now accepted although, in practice, programmes often fail to achieve their full potential. In this paper, we propose a conceptual model that situates screening programmes within the broader health system to understand the factors that influence their outcomes. We view the overall screening system as having multiple sub-systems to identify the population at risk, generate knowledge of effectiveness, maximise uptake, operate the programme, and optimise follow-up and assurance of subsequent treatment. Based on this model we have developed the Barriers to Effective Screening Tool (BEST) for analysing government-led, population-based screening programmes from a health systems perspective. Conceived as a self-assessment tool, we piloted the tool with key informants in six European countries (Estonia, Finland, Hungary, Italy, The Netherlands and Slovenia) to identify barriers to the optimal operation of population-based breast ca

The aim of this study was to identify barriers to effective cervical and colorectal cancers screening programmes in Europe. The Barriers to Effective Screening Tool (BEST), based on a health systems approach, was completed by teams of three to six experts on cancer screening in each of the six countries involved in leading the EU-TOPIA project (TOwards imProved screening for breast, cervical and colorectal cancer In All of Europe). While the basic components of screening systems and the challenges they face, such as low participation, are similar, there are also many differences, both in the structures underpinning particular functions, such as maintenance of populationregisters and monitoring outcomes, and the ways that they operate. Many of these lie outside the strict organisational boundaries of screening programmes. BEST offers a means to identify and prioritise issues for further detailed exploration. The holistic health systems approach to assessing barriers differs from previous approaches. Those focus on individual characteristics that determine participation. The approach described here provides additional opportunities to improve outcomes with measures that are largely within the control of those managing the health system.

Background False-positive histological diagnoses have the same consequences of overdiagnosis in terms of unnecessary treatment. The aim of this systematic review is to assess their frequency at needle core biopsy (CB) and/or surgical excision of the breast. Methods PubMed, Embase, Cochrane Library were systematically searched up to 30 October 2015. Eligibility criteria: cross-sectional studies assessing diagnostic accuracy of CB compared with surgical excision; studies assessing reproducibility of pathologists reading the same slides. Outcomes: false-positive rates; Misclassification of Benign as Malignant (MBM) histological diagnosis; K statistic. Independent reviewers extracted data and assessed quality using an adapted QUADAS-2 tool. Results Sixteen studies assessed CB false-positive rates. In 10 studies (41 989 screen-detected lesions), the range of false-positive rates was 0%-7.1%. Twenty-seven studies assessed pathologists' reproducibility. Studies with consecutive, random or stratified samples of all the specimens: at CB the MBM range was 0.25%-2.4% (K values 0.83-0.98); at surgical excision, it was 0.67%-1.2% (K values 0.86-0.94). Studies with enriched samples: the MBM range was 1.4%-6.2% (K values 0.57-0.86). Studies of cases selected for second opinion: the MBM range was 0.29%-12.2% (K values 0.48 and 0.50). Conclusions High heterogeneity of the included studies precluded formal pooling estimates. When considering studies of higher sample size or methodological quality, false-positive rates and MBM are around 1%. The impact of false-positive histological diagnoses of breast cancer on unnecessary treatment, as well as that of overdiagnosis, is not negligible and is of importance in clinical practice.

Objective Miss rate of polyps has been shown to be substantially lower with full-spectrum endoscopy (FUSE) compared with standard forward-viewing (SFV) colonoscopy in a tandem study at per polyp analysis. However, there is uncertainty on whether FUSE is also associated with a higher detection rate of colorectal neoplasia, especially advanced lesions, in per patient analysis. Methods Consecutive subjects undergoing colonoscopy following a positive faecal immunochemical test (FIT) by experienced endoscopists and performed in the context of a regional colorectal cancer population-screening programme were randomised between colonoscopy with either FUSE or SFV colonoscopy in seven Italian centres. Randomisation was stratified by gender, age group and screening history. Primary outcomes included detection rates of advanced adenomas (A-ADR), adenomas (ADR) and sessile-serrated polyps (SSPDR). Results Of 741 eligible subjects, 658 were randomised to either FUSE (n=328) or SFV (n=330) colonoscopy and included in the analysis. Overall, 293/658 and 143/658 subjects had at least one adenoma (ADR 44.5%) and advanced adenoma (A-ADR 21.7%), respectively, while SSP was the most advanced lesion in 18 cases (SSPDR 2.7%). ADR and A-ADR were 43.6% and 19.5% in the FUSE arm, and 45.5% and 23.9% in the SFV arm, with no difference for both ADR (OR for FUSE: 0.96, 95% CI 0.81 to 1.14) and A-ADR (OR for FUSE: 0.82, 95% CI 0.61 to 1.09). No difference in SSPDR or multiplicity was detected between the two arms. In the per polyp analysis, the mean number of adenomas and proximal adenomas per patient was 0.81±1.25 and 0.47±0.93 in the FUSE arm, and 0.85±1.33 and 0.48±0.96 in the SFV colonoscopy arm (p=NS for both comparisons). Conclusions No statistically significant difference in ADR and A-ADR between FUSE and SFV colonoscopy was detected in a per patient analysis in FIT-positive patients. Trial registration number ISRCTN10357435.

The general aim of this systematic review is to mitigate breast cancer (BC) overdiagnosis and overtreatment. The specific aim is to summarize available data on the occurrence and features of indolent invasive or in situ (DCIS) BC, and precisely survival of untreated cases, prevalence of occult cancers found in autopsies, frequency of regressive BC. PubMed, Embase and Cochrane Library were systematically searched up to 3/31/2014. Eligibility criteria were: cohort studies, case-control studies, uncontrolled case series assessing survival in women with a diagnosis of BC who did not receive treatment compared to treated women; case series of autopsies estimating the prevalence of undiagnosed BC; cohort studies, case-control studies, uncontrolled case series, case reports assessing the occurrence of spontaneous regression of BC in women with a confirmed histology diagnosis. Untreated BC: 8 cohort studies and 12 case series (3593 BC) were included. In three controlled cohort studies (diagnoses 1978-2006), the 5-years overall survival was 19-43%. Occult BC: 8 case series (2279 autopsies) were included. The prevalence of invasive BC undiagnosed during lifetime range was 0-1.5%, while for DCIS the range was 0.2-14.7%. Spontaneous regression: 2 cohort studies, 3 case reports, 1 case series included. In the cohort studies the relative risk of regression for screen detected compared with nonscreened BC was estimated as 1.2 and 1.1. It seems plausible that around 10% of invasive BC are not symptomatic during life, and that one fith of BC patients if untreated would be alive after 5 years. Around 1 of 10 screen-detected BC may regress according two studies.

In order to update the previous version of the European Code against Cancer and formulate evidence-based recommendations, a systematic search of the literature was performed according to the methodology agreed by the Code Working Groups. Based on the review, the 4th edition of the European Code against Cancer recommends:. "Take part in organized cancer screening programmes for:. •Bowel cancer (men and women)•Breast cancer (women)•Cervical cancer (women)." Organized screening programs are preferable because they provide better conditions to ensure that the Guidelines for Quality Assurance in Screening are followed in order to achieve the greatest benefit with the least harm. Screening is recommended only for those cancers where a demonstrated life-saving effect substantially outweighs the potential harm of examining very large numbers of people who may otherwise never have, or suffer from, these cancers, and when an adequate quality of the screening is achieved. EU citizens are recommended to participate in cancer screening each time an invitation from the national or regional screening program is received and after having read the information materials provided and carefully considered the potential benefits and harms of screening. Screening programs in the European Union vary with respect to the age groups invited and to the interval between invitations, depending on each country's cancer burden, local resources, and the type of screening test used. For colorectal cancer, most programs in the EU invite men and women starting at the age of 50-60 years, and from then on every 2 years if the screening test is the guaiac-based fecal occult blood test or fecal immunochemical test, or every 10 years or more if the screening test is flexible sigmoidoscopy or total colonoscopy. Most programs continue sending invitations to screening up to the age of 70-75 years.For breast cancer, most programs in the EU invite women starting at the age of 50 years, and not before the age o

This overview describes the principles of the 4th edition of the European Code against Cancer and provides an introduction to the 12 recommendations to reduce cancer risk. Among the 504.6 million inhabitants of the member states of the European Union (EU28), there are annually 2.64 million new cancer cases and 1.28 million deaths from cancer. It is estimated that this cancer burden could be reduced by up to one half if scientific knowledge on causes of cancer could be translated into successful prevention. The Code is a preventive tool aimed to reduce the cancer burden by informing people how to avoid or reduce carcinogenic exposures, adopt behaviours to reduce the cancer risk, or to participate in organised intervention programmes. The Code should also form a base to guide national health policies in cancer prevention. The 12 recommendations are: not smoking or using other tobacco products; avoiding second-hand smoke; being a healthy body weight; encouraging physical activity; having a healthy diet; limiting alcohol consumption, with not drinking alcohol being better for cancer prevention; avoiding too much exposure to ultraviolet radiation; avoiding cancer-causing agents at the workplace; reducing exposure to high levels of radon; encouraging breastfeeding; limiting the use of hormone replacement therapy; participating in organised vaccination programmes against hepatitis B for newborns and human papillomavirus for girls; and participating in organised screening programmes for bowel cancer, breast cancer, and cervical cancer.

In order to update the previous version of the European Code against Cancer and formulate evidence-based recommendations, a systematic search of the literature was performed according to the methodology agreed by the Code Working Groups. Based on the review, the 4th edition of the European Code against Cancer recommends: “Take part in organized cancer screening programmes for: • Bowel cancer (men and women)• Breast cancer (women)• Cervical cancer (women).”Organized screening programs are preferable because they provide better conditions to ensure that the Guidelines for Quality Assurance in Screening are followed in order to achieve the greatest benefit with the least harm. Screening is recommended only for those cancers where a demonstrated life-saving effect substantially outweighs the potential harm of examining very large numbers of people who may otherwise never have, or suffer from, these cancers, and when an adequate quality of the screening is achieved. EU citizens are recommended to participate in cancer screening each time an invitation from the national or regional screening program is received and after having read the information materials provided and carefully considered the potential benefits and harms of screening. Screening programs in the European Union vary with respect to the age groups invited and to the interval between invitations, depending on each country's cancer burden, local resources, and the type of screening test used For colorectal cancer, most programs in the EU invite men and women starting at the age of 50–60 years, and from then on every 2 years if the screening test is the guaiac-based fecal occult blood test or fecal immunochemical test, or every 10 years or more if the screening test is flexible sigmoidoscopy or total colonoscopy. Most programs continue sending invitations to screening up to the age of 70–75 years. For breast cancer, most programs in the EU invite women starting at the age of 50 years, and not before the age o