Effectiveness of Colonoscopy Screening vs Sigmoidoscopy Screening in Colorectal Cancer.

Importance: Randomized clinical screening trials have shown that sigmoidoscopy screening reduces colorectal cancer (CRC) incidence and mortality. Colonoscopy has largely replaced sigmoidoscopy for CRC screening, but long-term results from randomized trials on colonoscopy screening are still lacking. Objective: To estimate the additional screening benefit of colonoscopy compared with sigmoidoscopy. Design, Setting, and Participants: This comparative effectiveness simulation study pooled data on 358 204 men and women randomly assigned to sigmoidoscopy screening or usual care in 4 randomized sigmoidoscopy screening trials conducted in Norway, Italy, the US, and UK with inclusion periods in the years 1993 to 2001. The primary analysis of the study was conducted from January 19 to December 30, 2021. Intervention: Invitation to endoscopic screening. Main Outcomes and Measures: Primary outcomes were CRC incidence and mortality. Using pooled 15-year follow-up data, colonoscopy screening effectiveness was estimated assuming that the efficacy of colonoscopy in the proximal colon was similar to that observed in the distal colon in the sigmoidoscopy screening trials. The simulation model was validated using data from Norwegian participants in a colonoscopy screening trial. Results: This analysis included 358 204 individuals (181 971 women [51%]) aged 55 to 64 years at inclusion with a median follow-up time ranging from 15 to 17 years. Compared with usual care, colonoscopy prevented an estimated 50 (95% CI, 42-58) CRC cases per 100 000 person-years, corresponding to 30% incidence reduction (rate ratio, 0.70 [95% CI, 0.66-0.75]), and prevented an estimated 15 (95% CI, 11-19) CRC deaths per 100 000 person-years, corresponding to 32% mortality reduction (rate ratio, 0.68 [95% CI, 0.61-0.76]). The additional benefit of colonoscopy screening compared with sigmoidoscopy was 12 (95% CI, 10-14) fewer CRC cases and 4 (95% CI, 3-5) fewer CRC deaths per 100 000 person-years, corresponding to percentage point reductions of 6.9 (95% CI, 6.0-7.9) for CRC incidence and 7.6 (95% CI, 5.7-9.6) for CRC mortality. The number needed to switch from sigmoidoscopy to colonoscopy screening was 560 (95% CI, 486-661) to prevent 1 CRC case and 1611 (95% CI, 1275-2188) to prevent 1 CRC death. Conclusions and Relevance: The findings of this comparative effectiveness study assessing long-term follow-up after CRC screening suggest that there was an additional preventive effect on CRC incidence and mortality associated with colonoscopy screening compared with sigmoidoscopy screening, but the additional preventive effect was less than what was achieved by introducing sigmoidoscopy screening where no screening existed. The results probably represent the upper limit of what may be achieved with colonoscopy screening compared with sigmoidoscopy screening.

Comparing accuracy of tomosynthesis plus digital mammography or synthetic 2D mammography in breast cancer screening: baseline results of the MAITA RCT consortium.

AIM: The analyses here reported aim to compare the screening performance of digital tomosynthesis (DBT) versus mammography (DM). METHODS: MAITA is a consortium of four Italian trials, REtomo, Proteus, Impeto, and MAITA trial. The trials adopted a two-arm randomised design comparing DBT plus DM (REtomo and Proteus) or synthetic-2D (Impeto and MAITA trial) versus DM; multiple vendors were included. Women aged 45 to 69 years were individually randomised to one round of DBT or DM. FINDINGS: From March 2014 to February 2022, 50,856 and 63,295 women were randomised to the DBT and DM arm, respectively. In the DBT arm, 6656 women were screened with DBT plus synthetic-2D. Recall was higher in the DBT arm (5·84% versus 4·96%), with differences between centres. With DBT, 0·8/1000 (95% CI 0·3 to 1·3) more women received surgical treatment for a benign lesion. The detection rate was 51% higher with DBT, ie. 2·6/1000 (95% CI 1·7 to 3·6) more cancers detected, with a similar relative increase for invasive cancers and ductal carcinoma in situ. The results were similar below and over the age of 50, at first and subsequent rounds, and with DBT plus DM and DBT plus synthetic-2D. No learning curve was appreciable. Detection of cancers >= 20 mm, with 2 or more positive lymph nodes, grade III, HER2-positive, or triple-negative was similar in the two arms. INTERPRETATION: Results from MAITA confirm that DBT is superior to DM for the detection of cancers, with a possible increase in recall rate. DBT performance in screening should be assessed locally while waiting for long-term follow-up results on the impact of advanced cancer incidence.

Plasma microRNA ratios associated with breast cancer detection in a nested case-control study from a mammography screening cohort.

Mammographic breast cancer screening is effective in reducing breast cancer mortality. Nevertheless, several limitations are known. Therefore, developing an alternative or complementary non-invasive tool capable of increasing the accuracy of the screening process is highly desirable. The objective of this study was to identify circulating microRNA (miRs) ratios associated with BC in women attending mammography screening. A nested case-control study was conducted within the ANDROMEDA cohort (women of age 46-67 attending BC screening). Pre-diagnostic plasma samples, information on life-styles and common BC risk factors were collected. Small-RNA sequencing was carried out on plasma samples from 65 cases and 66 controls. miR ratios associated with BC were selected by two-sample Wilcoxon test and lasso logistic regression. Subsequent assessment by RT-qPCR of the miRs contained in the selected miR ratios was carried out as a platform validation. To identify the most promising biomarkers, penalised logistic regression was further applied to candidate miR ratios alone, or in combination with non-molecular factors. Small-RNA sequencing yielded 20 candidate miR ratios associated with BC, which were further assessed by RT-qPCR. In the resulting model, penalised logistic regression selected seven miR ratios (miR-199a-3p_let-7a-5p, miR-26b-5p_miR-142-5p, let-7b-5p_miR-19b-3p, miR-101-3p_miR-19b-3p, miR-93-5p_miR-19b-3p, let-7a-5p_miR-22-3p and miR-21-5p_miR-23a-3p), together with body mass index (BMI), menopausal status (MS), the interaction term BMI * MS, life-style score and breast density. The ROC AUC of the model was 0.79 with a sensitivity and specificity of 71.9% and 76.6%, respectively. We identified biomarkers potentially useful for BC screening measured through a widespread and low-cost technique. This is the first study reporting circulating miRs for BC detection in a screening setting. Validation in a wider sample is warranted.Trial registration: The Andromeda prospective cohort study protocol was retrospectively registered on 27-11-2015 (NCT02618538).

EuroMed Cancer Network contributions to eliminating cervical cancer in low- and middle-income Mediterranean countries.

Background: Cervical cancer places a significant burden on low- and middle-income countries (LMICs). The EuroMed Cancer Network (EuMedCN) brings together cancer experts and stakeholders from the Mediterranean countries to promote sustainable cancer screening and support implementation of the WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem. Aim: To highlight the constructive role of EuMedCN in mitigating inequalities in access to cervical cancer prevention and screening across the Mediterranean LMICs. Methods: Through its workshops and meetings, EuMedCN members discussed new developments in cancer prevention and control, and how best to translate the WHO Global Strategy to Accelerate the Elimination of Cervical Cancer as a Public Health Problem into public health policies in the Mediterranean LMICs. This led to targeted actions in the selected countries. Results: Seven priority actions were implemented to improve cervical cancer screening in the Mediterranean LMICs. EuMedCN supported organized screening, new pilot technologies and enhancement of evaluation systems. Integrating cervical cancer screening into other disease programmes and fostering multidisciplinary networks were promoted as key to achieving targets of the WHO global strategy. Conclusion: International networks, such as EuMedCN, have the potential to bring together experts and stakeholders to share experiences and catalyse resource mobilization. They can support affordable and synergistic solutions for cervical cancer prevention.

15-Year Benefits of Sigmoidoscopy Screening on Colorectal Cancer Incidence and Mortality : A Pooled Analysis of Randomized Trials.

BACKGROUND: The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain. OBJECTIVE: To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality. DESIGN: Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening. SETTING: Norway, the United States, the United Kingdom, and Italy. PARTICIPANTS: Women and men aged 55 to 64 years at enrollment. INTERVENTION: Sigmoidoscopy screening. MEASUREMENTS: Primary end points were cumulative incidence rate ratio (IRR) and mortality rate ratio (MRR) and rate differences after 15 years of follow-up comparing screening versus usual care in intention-to-treat analyses. Stratified analyses were done by sex, cancer site, and age at screening. RESULTS: Analyses comprised 274 952 persons (50.7% women), 137 493 in the screening and 137 459 in the usual care group. Screening attendance was 58% to 84%. After 15 years, the rate difference for CRC incidence was 0.51 cases (95% CI, 0.40 to 0.63 cases) per 100 persons and the IRR was 0.79 (CI, 0.75 to 0.83). The rate difference for CRC mortality was 0.13 deaths (CI, 0.07 to 0.19 deaths) per 100 persons, and the MRR was 0.80 (CI, 0.72 to 0.88). Women had less benefit from screening than men for CRC incidence (IRR for women, 0.84 [CI, 0.77 to 0.91]; IRR for men, 0.75 [CI, 0.70 to 0.81]; P = 0.032 for difference) and mortality (MRR for women, 0.91 [CI, 0.77 to 1.17]; MRR for men, 0.73 [CI, 0.64 to 0.83]; P = 0.025 for difference). There was no statistically significant difference in screening effect between persons aged 55 to 59 years and those aged 60 to 64 years. LIMITATION: Data from the U.K. trial were less granular because of privacy regulations. CONCLUSION: This pooled analysis of all large randomized trials of sigmoidoscopy screening demonstrates a significant and sustained effect of sigmoidoscopy on CRC incidence and mortality for 15 years. PRIMARY FUNDING SOURCE: Health Fund of South-East Norway.

Promoting healthy lifestyle habits among participants in cancer screening programs: Results of the randomized controlled Sti.Vi study.

Background: Unhealthy diets, physical inactivity, alcohol and tobacco consumption are among the leading risk factors for non-communicable diseases. It is estimated that around 40% of cancers could be prevented by adopting healthy lifestyles. Design and methods: The Stili di Vita (Sti.Vi) study was a randomized study for assessing the impact of healthy lifestyle interventions on anthropometric measures, metabolic parameters, and health outcomes among participants of cancer screening programs in Turin (Italy). Eligible women aged 50-54 years, invited to biennial mammography screening, and 58-years-old men and women, invited to a once-only sigmoidoscopy for colorectal cancer (CRC) screening were randomly allocated to Diet group (DG), Physical Activity group (PAG), Physical Activity plus Diet group (PADG), or control group (CG). Physical and eating habits, metabolic and anthropometric measurements, repeatedly collected, were the study outcomes. The active intervention, offered to participants assigned to the DG, PAG, and PADG arms, consisted of a basic module and an advanced module. The effect of the interventions was estimated through logistic regression or a difference in differences approach. A multiple imputation procedure was implemented to deal with missing values and q-values have been calculated in the presence of multiple hypothesis testing. Results: Out of the 8442 screened attendees, 1270 signed informed consent, while 1125 participants accomplished the baseline visit. Participants were equally distributed across the four treatments as following: 273 (24.3%) in DG, 288 (25.6%) in the PAG, 283 (25.1%) in PADG, and 281 (25%) in the CG. Participants assigned to DG or PADG increased their consumption of whole grains (OR = 1.77, 95% CI: 1.20-2.60 and OR = 1.55, 95% CI: 1.06-2.27, respectively) and legumes (OR = 1.77, 95% CI: 1.12-2.79 and OR = 2.24, 95% CI: 1.41-3.57, respectively), with respect to CG. The participants randomized to DG reduced processed meat and increased fruit consumption (OR = 2.57, 95% CI: 1.76-3.76 and OR = 2.38, 95% CI: 1.12-5.06, respectively). The effects were more evident in the CRC screening subgroup. No relevant difference was observed between PAG and CG. No impact was observed on physical activity habits. Conclusions: Our findings suggest that active interventions can increase awareness and induce diet changes. However, participation rate and compliance to the courses was quite low, innovative strategies to enhance participants' retention are needed, with the ultimate goal of increasing awareness and inducing positive lifestyle changes.

A randomised controlled trial of digital breast tomosynthesis vs digital mammography as primary screening tests: Screening results over subsequent episodes of the Proteus Donna study.

Proteus Donna is a randomised controlled trial aimed at prospectively evaluating screening with digital breast tomosynthesis (DBT), including interval cancer detection (ICD) and cancer detection (CD) in the analysis as a cumulative measure over subsequent screening episodes. Consenting women aged 46 to 68 attending the regional Breast Screening Service were randomly assigned to conventional digital mammography (DM, control arm) or DBT in addition to DM (DBT, study arm). At the subsequent round all participants underwent DM. Thirty-six months follow-up allowed for the identification of cancers detected in the subsequent screening and interscreening interval. Relative risk (RR) and 95% confidence interval (95% CI) were computed. Cumulative CD and Nelson-Aalen incidence were analysed over the follow-up period. Between 31 December 2014 and 31 December 2017, 43 022 women were randomised to DM and 30 844 to DBT. At baseline, CD was significantly higher (RR: 1.44, 95% CI: 1.21-1.71) in the study arm. ICD did not differ significantly between the two arms (RR: 0.92, 95% CI: 0.62-1.35). At subsequent screening with DM, the CD was lower (nearly significant) in the study arm (RR: 0.83, 95% CI: 0.65-1.06). Over the follow-up period, the cumulative CD (comprehensive of ICD) was slightly higher in the study arm (RR: 1.15, 95% CI: 1.01-1.31). The Nelson-Aalen cumulative incidence over time remained significantly higher in the study arm for approximately 24 months. Benign lesions detection was higher in the study arm at baseline and lower at subsequent tests. Outcomes are consistent with a lead time gain of DBT compared to DM, with an increase in false positives and moderate overdiagnosis.

Long-Term Follow-up of the Italian Flexible Sigmoidoscopy Screening Trial.

BACKGROUND: Recent reports showed that the protective effect of flexible sigmoidoscopy (FS) screening was maintained up to17 years, although differences were reported by sex. OBJECTIVE: To assess long-term reduction of colorectal cancer (CRC) incidence and mortality after a single FS screening. DESIGN: Parallel randomized controlled trial. (ISRCTN registry number: 27814061). SETTING: 6 centers in Italy. PARTICIPANTS: Persons aged 55 to 64 years expressing interest in having FS screening if invited, recruited from 1995 to 1999 and followed until 2012 (incidence) and 2014 to 2016 (mortality). INTERVENTION: Eligible persons were randomly assigned (1:1 ratio) to either the once-only FS screening group or control (usual care) group. MEASUREMENTS: Incidence and mortality rate ratios (RRs) and rate differences. RESULTS: A total of 34 272 persons (17 136 in each group) were included in the analysis; 9911 participants had screening in the intervention group. Median follow-up was 15.4 years for incidence and 18.8 years for mortality. Incidence of CRC was reduced by 19% (RR, 0.81 [95% CI, 0.71 to 0.93]) in the intention-to-treat (ITT) analysis, comparing the intervention with the control group, and by 33% (RR, 0.67 [CI, 0.56 to 0.81]) in the per protocol (PP) analysis, comparing participants screened in the intervention group with the control persons. Colorectal cancer mortality was reduced by 22% (RR, 0.78 [CI, 0.61 to 0.98]) in the ITT analysis and by 39% (RR, 0.61 [CI, 0.44 to 0.84]) in the PP analysis. Incidence of CRC was statistically significantly reduced among both men and women. Colorectal cancer mortality was statistically significantly reduced among men (ITT RR, 0.73 [CI, 0.54 to 0.97]) but not among women (ITT RR, 0.90 [CI, 0.59 to 1.37]). LIMITATION: Self-selection of volunteers from the general population sample targeted for recruitment may limit generalizability. CONCLUSION: The strong protective effect of a single FS screening for CRC incidence and mortality was maintained up to 15 and 19 years, respectively. PRIMARY FUNDING SOURCE: Italian Association for Cancer Research, Italian National Research Council, Istituto Oncologico Romagnolo, Fondo "E. Tempia," University of Milan, and Local Health Unit ASL-Torino.

The EU-TOPIA evaluation tool: An online modelling-based tool for informing breast, cervical, and colorectal cancer screening decisions in Europe.

BACKGROUND: Aiming to support European countries in improving their breast, cervical, and colorectal cancer (CRC) screening programmes, the EU-TOPIA consortium has developed an online user-friendly tool (the EU-TOPIA evaluation tool; https://miscan.eu-topia.org) based on the Microsimulation Screening Analysis (MISCAN) model. METHODS: We designed an online platform that allows stakeholders to use their country-specific data (demographic, epidemiological, and cancer screening information) to quantify future harms and benefits of different cancer screening scenarios in their country. Current cancer screening programmes and impacts of potential changes in screening protocols (such as extending target ages or increasing screening attendance) can be simulated. Results are scaled to the country-specific population. To illustrate the tool, we used the tool to simulate two different CRC screening scenarios in the Netherlands: biennial fecal immunochemical testing (FIT) in ages 55-75 and colonoscopy every ten years in ages 55-75. Data from the Dutch screening programme was used to inform both scenarios. RESULTS: A total of 482,700 CRC cases and 178,000 CRC deaths were estimated in the Netherlands with FIT screening (for individuals aged 40-100 years, 2018-2050), with 47.3 million FITs performed (1.92 million positives of which 1.64 million adhered to diagnostic colonoscopy). With colonoscopy screening, CRC incidence and mortality were, respectively, up to 17% and 14% lower than in the current FIT screening programme, requiring, however, a colonoscopy demand that was 7-fold higher. CONCLUSIONS: Our study presents an essential online tool for stakeholders and medical societies to quantify estimates of benefits and harms of early cancer detection in Europe.

Measures of longitudinal adherence to fecal-based colorectal cancer screening: Literature review and recommended approaches.

The success of fecal occult blood-based colorectal cancer screening programs is dependent on repeating screening at short intervals (ie, every 1-2 years). We conducted a literature review to assess measures that have been used to assess longitudinal adherence to fecal-based screening. Among 46 citations identified and included in this review, six broad classifications of longitudinal adherence were identified: (a) stratified single-round attendance, (b) all possible adherence permutations, (c) consistent/inconsistent/never attendance, (d) number of times attended, (e) program adherence and (f) proportion of time covered. Advantages and disadvantages of these measures are described, and recommendations on which measures to use based on data availability and scientific question are also given. Stratified single round attendance is particularly useful for describing the yield of screening, while programmatic adherence measures are best suited to evaluating screening efficacy. We recommend that screening programs collect detailed longitudinal, individual-level data, not only for the screening tests themselves but additionally for diagnostic follow-up and surveillance exams, to allow for maximum flexibility in reporting adherence patterns using the measure of choice.

Disability-Adjusted Life Years Averted Versus Quality-Adjusted Life Years Gained: A Model Analysis for Breast Cancer Screening.

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.

Development and Validation of Three Regional Microsimulation Models for Predicting Colorectal Cancer Screening Benefits in Europe.

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.

Performance indicators in breast cancer screening in the European Union: A comparison across countries of screen positivity and detection rates.

Comparable performance indicators for breast cancer screening in the European Union (EU) have not been previously reported. We estimated adjusted breast cancer screening positivity rate (PR) and detection rates (DR) to investigate variation across EU countries. For the age 50-69 years, the adjusted EU-pooled PR for initial screening was 8.9% (cross-programme variation range 3.2-19.5%) while DR of invasive cancers was 5.3/1,000 (range 3.8-7.4/1,000) and DR of ductal carcinoma in situ (DCIS) was 1.3/1,000 (range 0.7-2.7/1,000). For subsequent screening, the adjusted EU-pooled PR was 3.6% (range 1.4-8.4%), the DR was 4.0/1,000 (range 2.2-5.8/1,000) and 0.8/1,000 (range 0.5-1.3/1,000) for invasive and DCIS, respectively. Adjusted performance indicators showed remarkable heterogeneity, likely due to different background breast cancer risk and awareness between target populations, and also different screening protocols and organisation. Periodic reporting of the screening indicators permits comparison and evaluation of the screening activities between and within countries aiming to improve the quality and the outcomes of screening programmes. Cancer Screening Registries would be a milestone in this direction and EU Screening Reports provide a fundamental contribution to building them.

Effect of organised cervical cancer screening on cervical cancer mortality in Europe: a systematic review.

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 were used to assess the risk of bias of the included studies. RESULTS: Ten observational studies were included: seven cohort and three case-control studies. No randomised controlled trials were found, and there were no eligible studies from the eastern and southern part of Europe. Among the eligible studies, seven were conducted in the twentieth century; they scored lower on the risk of bias assessment. CC mortality reduction for women attending organised screening vs. non-attenders ranged from 41% to 92% in seven studies. Reductions were similar in Western (45-92%) and Northern (41-87%) Europe and were higher in the three more recent studies (66-92%). For invited vs. non-invited women, this reduction ranged from 17% to 79% in five studies. CONCLUSION: Although data were lacking in Southern and Eastern Europe and the effect size varied between countries and studies, this systematic review provides evidence that organised CC screening reduces CC mortality in those parts of Europe where CC screening was implemented and monitored.

Key issues that need to be considered while revising the current annex of the European Council Recommendation (2003) on cancer screening.

The 2003 European Council recommendation urging the Member States to introduce or scale up breast, cervical and colorectal cancer screening through an organized population-based approach has had a remarkable impact. We argue that the recommendation needs to be updated for at least two sets of reasons. First, some of the current clinical guidelines include new tests or protocols that were not available at the time of the Council document. Some have already been adopted by organized screening programs, such as newly defined age ranges for mammography screening, Human Papillomavirus (HPV)-based cervical cancer screening, fecal immunochemical test (FIT) and sigmoidoscopy for colorectal cancer screening. Second, the outcomes of randomized trials evaluating screening for lung and prostate cancer have been published recently and the balance between harms and benefits needs to be pragmatically assessed. In the European Union, research collaboration and networking to exchange and develop best practices should be regularly supported by the European Commission. Integration between primary and secondary preventive strategies through comprehensive approaches is necessary not only to maximize the reduction in cancer burden but also to control the rising trend of other noncommunicable diseases sharing the same risk factors.

Evidence for reducing cancer-specific mortality due to screening for breast cancer in Europe: A systematic review.

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 36 cohort studies, 17 case-control studies and 7 RCTs. None were from Eastern Europe. The quality of the included studies varied: Nineteen of these studies were of very good or good quality. Of those, the reduction in breast cancer mortality in attenders versus non-attenders ranged between 33% and 43% (Northern Europe), 43%-45% (Southern Europe) and 12%-58% (Western Europe). The estimates ranged between 4% and 31% in invited versus non-invited. CONCLUSION: This systematic review provides evidence that organised screening reduces breast cancer mortality in all European regions where screening was implemented and monitored, while quantification is still lacking for Eastern Europe. The wide range of estimates indicates large differences in the evaluation designs between studies, rather than in the effectiveness of screening.

Impact of colorectal cancer screening on cancer-specific mortality in Europe: A systematic review.

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.