Search

The effectiveness of screening for colorectal cancer (CRC) by sex and age in randomized trials is uncertain.To evaluate the 15-year effect of sigmoidoscopy screening on CRC incidence and mortality.Pooled analysis of 4 large-scale randomized trials of sigmoidoscopy screening.Norway, the United States, the United Kingdom, and Italy.Women and men aged 55 to 64 years at enrollment.Sigmoidoscopy screening.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.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];Data from the U.K. trial were less granular because of privacy regulations.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.Health Fund of South-East Norway.

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.

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.

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.

ObjectiveTo estimate the predictive role of faecal haemoglobin (f-Hb) concentration among subjects with faecal immunochemical test (FIT) results below the positivity cut-off for the subsequent risk of advanced neoplasia (AN: colorectal cancer—CRC—or advanced adenoma).DesignProspective cohort of subjects aged 50–69 years, undergoing their first FIT between 1 January 2004 and 31 December 2010 in four population-based programmes in Italy.MethodsAll programmes adopted the same analytical procedure (OC Sensor, Eiken Japan), performed every 2 years, on a single sample, with the same positivity cut-off (20 µg Hb/g faeces). We assessed the AN risk at subsequent exams, the cumulative AN detection rate (DR) over the 4-year period following the second FIT and the interval CRC (IC) risk following two negative FITs by cumulative amount of f-Hb concentration over two consecutive negative FITs, using multivariable logistic regression models and the Kaplan-Meier method.ResultsThe cumulative probability of a positive FIT result over the subsequent two rounds ranged between 7.8% (95% CI 7.5 to 8.2) for subjects with undetectable f-Hb at the initial two tests (50% of the screenees) and 48.4% (95% CI 44.0 to 53.0) among those (0.7% of the screenees) with a cumulative f-Hb concentration ≥20 µg/g faeces. The corresponding figures for cumulative DR were: 1.4% (95% CI 1.3 to 1.6) and 25.5% (95% CI 21.4 to 30.2) for AN; 0.17% (95% CI 0.12 to 0.23) and 4.5% (95% CI 2.8 to 7.1) for CRC. IC risk was also associated with cumulative f-Hb levels.ConclusionThe association of cumulative f-Hb concentration with subsequent AN and IC risk may allow to design tailored strategies to optimise the utilisation of endoscopy resources: subjects with cumulative f-Hb concentration ≥20 µg/g faeces over two negative tests could be referred immediately for total colonoscopy (TC), while screening interval might be extended for those with undetectable f-Hb.

The aim of this study was to describe the compliance of the population-based cancer screening programmes in the European Union Member States to the invitation strategies enumerated in the European Guidelines and the impact of such strategies on the invitational coverage. Experts in screening programme monitoring from the respective countries provided data. Coverage by invitation was calculated as the proportion of individuals in the target age range receiving a screening invitation over the total number of annualized eligible population. The invitation strategies of 30 breasts, 25 cervical and 27 colorectal national or regional population-based screening programmes are described. Individual mail invitations are sent by 28 breasts, 20 cervical and 25 colorectal screening programmes. Faecal occult blood test kits are sent by post in 17 of the colorectal cancer screening programmes. The majority of programmes claimed to have a population registry, although some use health insurance data as the database for sending invitations. At least 95% invitation coverage was reached by 16 breast, six cervical and five colorectal screening programmes. Majority of the programmes comply with the invitation strategies enumerated in the European guidelines, although there is still scope for improvements. Coverage by invitation is below the desirable level in many population-based cancer screening programmes in European Union.

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.

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.

The success of fecal occult blood-based colorectal cancer screening programs is dependent on repeating screening at short intervals (i.e., every one to two 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: (1) stratified single-round attendance, (2) all possible adherence permutations, (3) consistent/inconsistent/never attendance, (4) number of times attended, (5) program adherence, and (6) 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.

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.

Available evidence on axillary surgery has accumulated dramatically in the last two decades in favor of less invasive care. The aim of this paper is to study 16-years trends in the surgical management of the axilla in a large population-based data set of screen-detected breast cancers in Italy and to document at what extent recommendations have been adopted in actual clinical care.This is a retrospective cohort study documenting the surgical management of the axilla in primary breast cancer patients over time. We retrieved from the Italian database of screen-detected cancers 41213 cases diagnosed in women aged 50-69 between years 2000 and 2015 in twelve Italian Regions.In pN0 cases, an increasing trend (p 0.001) in the number of patients who received sentinel lymph node biopsy (SLNB) as the only axillary staging procedure was observed. In pN + cases SLNB was the only staging procedure in an increasing number of patients (p 0.001) especially since the publication of the ACOSOG-Z0011 paper. In ductal carcinoma in situ (DCIS) SLNB was more frequent in mastectomies and in high grade and large lesions. However, 45% of low grade, small DCIS over the whole time period had some form of axillary surgery.This large series of screen-detected cases documents a strong time trend in the direction of reducing axillary surgery and hence potential harms from treatment. The continuing practice of SLNB in low risk DCIS is of concern in an era of increasing awareness towards overdiagnosis and overtreatment.

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 cancer screening programmes. The pilot provided valuable feedback on the barriers affecting breast cancer screening programmes and stimulated a greater recognition among those operating them of the need to take a health systems perspective. In addition, the pilot led to further development of the tool and provided a foundation for further research into how to overcome the identified barriers.

The second report on the implementation status of cancer screening in European Union (EU) was published in 2017. The report described the implementation status, protocols and organization (updated till 2016) and invitation coverage (for index year 2013) of breast, cervical and colorectal cancer screening in the EU. Experts in screening programme monitoring (N=80) from the EU Member States having access to requisite information in their respective countries provided data on breast, cervical and colorectal cancer screening through online questionnaires. Data was collected for screening performed in the framework of publicly mandated programmes only. Filled in questionnaires were received from 26 Member States for all three sites and from one Member State for breast cancer only. Substantial improvement in screening implementation using population-based approach was documented. Among the age-eligible women, 94.7% were residents of Member States implementing or planning population-based breast cancer screening in 2016, compared to 91.6% in 2007. The corresponding figures for cervical cancer screening were 72.3% and 51.3% in 2016 and 2007 respectively. Most significant improvement was documented for colorectal cancer screening with roll-out ongoing or completed in 17 Member States in 2016, compared to only five in 2007. So the access to population-based screening increased to 72.4% of the age-eligible populations in 2016 as opposed to only 42.6% in 2007. The invitation coverage was highly variable, ranging from 0.2%-111% for breast cancer, 7.6%-105% for cervical cancer and 1.8%-127% for colorectal cancer in the target populations. In spite of the considerable progress, much work remains to be done to achieve optimal effectiveness. Continued monitoring, regular feedbacks and periodic reporting are needed to ensure the desired impacts of the programmes. This article is protected by copyright. All rights reserved.

Testicular cancer is considered to originate from an impaired differentiation of fetal germ cells, but puberty could represent another time window of susceptibility. Our study aimed at investigating the association between environmental exposures acting during puberty/adolescence (13-19 years of age) and the risk of testicular cancer. We used data of the EPSAM study, a case-control study on germ-cell testicular cancer conducted in the province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Histologically confirmed cases (n = 255) and controls (n = 459) completed a postal questionnaire focusing in particular on the pubertal period (namely age 13 years) with questions on physical activity (competitive sports, gardening), lifestyle (alcohol consumption, smoking), occupational history and medical conditions. All analyses were adjusted for the matching variables, cryptorchidism and educational level. Having done at least one competitive sport during puberty (odds ratio [OR]: 0.72, 95% confidence interval: 0.52-1.00), gardening activities during puberty (OR: 0.62, 0.42-0.94) and having a lower weight than peers during puberty (OR: 0.64, 0.42-0.97) were all inversely associated with the risk of testicular cancer. No evidence of association between smoking or alcohol consumption during puberty and the risk of testicular cancer was observed. Regarding agriculture-related occupations, we found an association with the risk of testicular cancer both for occasional jobs during puberty (OR: 2.40, 95% CI: 1.08-5.29) and ever employment in adolescence (OR: 2.59, 95% CI: 0.83-8.10). Our results suggest that postnatal exposures could play a role in testicular cancer aetiology, at least when acting in puberty or adolescence.

In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age (25years) for cervical cancer (CC) screening from 2017. The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention. The ONS (National Screening Monitoring Centre) Directive and the GISCi (Italian Group for Cervical Screening) identified the consensus conference as the most suitable method for addressing this topic. A summary of consensus recommendations is reported here. The main objective was to define the best screening methods in girls vaccinated against HPV and the knowledge required for defining evidence-based screening strategies. A Jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews of literature and evidence. The Jury considered changing the screening protocols for girls vaccinated in their twelfth year as appropriate. Tailored screening protocols based on vaccination status could be replaced by "one size fits all" protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their fifteenth year or later, the current protocol should be kept.

BackgroundFalse-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.MethodsPubMed, 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.ResultsSixteen 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).ConclusionsHigh 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.

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.

Nuclear grade is an important indicator of the biological behaviour of ductal carcinoma in situ (DCIS). De-escalation of treatment has been suggested for low-grade DCIS. Our aim is to estimate the relative rate of progression of DCIS by nuclear grade by analysing the distribution of nuclear grade by detection at initial or subsequent screening. We asked International Cancer Screening Network sites to complete, based on their screening and clinical databases, an aggregated data file on DCIS detection, diagnosis and treatment. Eleven screening programs reported 5068 screen-detected pure DCIS in nearly 7 million screening tests in women 50–69 years of age. For all programs combined, low-grade DCIS were 20.1% (range 11.4–31.8%) of graded DCIS, intermediate grade 31.0% and high grade 48.9%. Detection rates decreased more steeply from initial to subsequent screening in low compared to high-grade DCIS: the ratios of subsequent to initial detection rates were 0.39 for low grade, 0.51 for intermediate grade, and 0.75 for high grade (p

Objective Several European countries are implementing organized colorectal cancer (CRC) screening programmes using faecal immunochemical test (FIT) and/or flexible sigmoidoscopy (FS), but the cost-effectiveness of these programmes is not yet available. We aimed to assess cost-effectiveness, based on data from the established Piedmont screening programme. Methods Using the Piedmont programme data, a Markov model was constructed comparing three strategies in a simulated cohort of 100,000 subjects: single FS, biennial FIT, or sequential strategy (FS + FIT offered to FS non-responders). Estimates for CRC incidence and mortality prevention were derived from studies of organized screening. Cost analysis for FS and FIT was based on data from organized programmes. Incremental cost-effectiveness ratios (ICER) between the different strategies were calculated. Sensitivity and probabilistic analyses were performed. Results Direct costs for FS, and for FIT at first and subsequent rounds, were estimated as €160, €33, and €21, respectively. All the simulated strategies were effective (10–17% CRC incidence reduction) and cost-effective vs. no screening (ICER Conclusions Organized CRC screening programmes are highly cost-effective, irrespective of the test selected. A sequential approach with FS and FIT appears the most cost-effective option. A single FS is the least expensive, but convenient, approach.

AimTo compare acceptability and diagnostic accuracy of a recently available faecal immunochemical test (FIT) system (HM-JACKarc) with the FIT routinely used in an established screening programme (OC-Sensor).DesignRandomised controlled trial (ISRCTN20086618) within a population-based colorectal cancer (CRC) screening programme. Subjects eligible for invitation in the Umbria Region (Italy) programme were randomised (ratio 1:1) to be screened using one of the FIT systems.ResultsScreening uptake among the 48 888 invitees was the same for both systems among subjects invited in the first round and higher with OC-Sensor than with HM-JACKarc (relative risk (RR): 1.03; 95% CI 1.02 to 1.04) among those invited in subsequent rounds. Positivity rate (PR) was similar with OC-Sensor (6.5%) as with HM-JACKarc (6.2%) among subjects performing their first FIT screening and higher with OC-Sensor (5.6%, RR: 1.25, 95% CI 1.12 to 1.40) than with HM-JACKarc (4.4%) among those screened in previous rounds. Positive predictive value (PPV) (OC-Sensor: 25.9%, HM-JACKarc: 25.6%) and detection rate (DR) (OC-Sensor: 1.40%; HM-JACKarc: 1.42%) for advanced neoplasia (AN: CRC + advanced adenoma) were similar among subjects performing their first FIT screening. The differences in the AN PPV (OC-Sensor: 20.3%, HM-JACKarc: 22.6%) and DR (OC-Sensor: 0.96%, HM-JACKarc: 0.83%) among those screened in previous rounds were not statistically significant. The number needed to scope to detect one AN was 3.9 (95% CI 5.8 to 2.9) and 3.9 (95% CI 5.5 to 2.9) at first and 4.9 (95% CI 5.8 to 4.2) and 4.4 (95% CI 5.3 to 3.7) at subsequent screening, with OC-Sensor and HM-JACKarc, respectively.ConclusionsOur results suggest that acceptability and diagnostic performance of HM-JACKarc and of OC-Sensor systems are similar in a screening setting.Trial registration numberISRCTN20086618; Results.

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.

The etiology of testicular cancer is largely unexplained. Research has mainly focused on prenatal exposures, especially to sex hormones, while less attention has been paid to exposures that may act also postnatally. As baldness has been previously associated with testicular cancer risk we focused on baldness and body hairiness, which are both associated with androgen activity. We used data of the Postnatal Exposures and Male Health (EPSAM) study, a case-control study on testicular cancer conducted in the Province of Turin, Italy, involving cases diagnosed between 1997 and 2008. Information was collected using mailed questionnaires. Analyses included 255 cases and 459 controls. We calculated ORs and 95% CIs to estimate testicular cancer risk among those who developed baldness and among those with body hairiness. We found an inverse association between testicular cancer and baldness (OR: 0.67, 95% CI: 0.46-0.98) and body hairiness (OR: 0.78, 95% CI: 0.53-1.16), although the latter had wider CIs. The inverse association between baldness and testicular cancer is consistent with the results from previous studies. These results suggest that androgens activity may influence testicular cancer risk.

Background and Aims Second-generation colon capsule endoscopy (CCE-2) has shown promising accuracy for the diagnosis of overall neoplasia. Advanced neoplasia (AN) represents the main target of colorectal cancer screening programs. Our aim was to assess the diagnostic accuracy of CCE-2 for the detection of AN in patients with a positive result for the fecal immunochemical test (FIT) who are undergoing screening. Methods Patients aged 50 to 69 years with a positive result for the FIT in 4 population screening programs in Italy and Spain were enrolled. Screenees were asked to undergo CCE-2, followed by traditional colonoscopy (TC). TC was performed the same day or the following morning. Bowel preparation included a split-dose polyethylene glycol–based regimen, with sodium phosphate (NaP) with gastrografin as boosters. The CCE-2 video was read by an endoscopist blinded to the results of TC. The main outcomes were CCE-2 accuracy in terms of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for AN when using 2 different size thresholds for TC referral (ie, polyps ≥6 mm and ≥10 mm). Results Two hundred twenty-two patients were enrolled, and 178 patients completed both CCE-2 and TC (87.7%). Overall, 59 cases of AN were detected at TC. CCE-2 sensitivity was 90%, specificity was 66.1%, PPV was 57.4%, and NPV was 92.9% for AN when using a 6-mm cut-off (TC referral rate, 52.8%) and 76.7%, 90.7%, 80.7%, and 88.4% when using a 10-mm cut-off (TC referral rate, 32%), respectively. CCE-2 detected that 8 of 9 already developed colorectal cancers. Among the 41 false positives at the 6-mm cut-off, 34 (82.9%) presented with a nonadvanced adenoma at TC. Mean transit time was 4 hours and 4 minutes, and ≥70% of patients excreted the capsule within 5 hours. Conclusions In an enriched disease setting, we showed the high sensitivity of CCE-2 for the diagnosis of AN at a 6-mm cut-off. The apparently low CCE-2 specificity is related to the choice of AN as the main outcome. (Clinical trial registration number: ISRCTN 62158762.)

ObjectiveTo present comparative data about the performance of colorectal cancer (CRC) screening programmes in the European Union Member States (EU MSs).DesignCross-sectional study. We analysed key performance indicators—participation rate, positivity rate (PR), detection rate (DR) and positive predictive value for adenomas and CRC—based on the aggregated quantitative data collected for the second EU screening report. We derived crude and pooled (through a random effects model) estimates to describe and compare trends across different MSs/regions and screening protocols.ResultsParticipation rate was higher in countries adopting faecal immunochemical test (FIT) (range: 22.8%–71.3%) than in those using guaiac faecal occult blood test (gFOBT) (range 4.5%–66.6%), and it showed a positive correlation (ρ=0.842, pConclusionsThe variability in the results of quality indicators across population-based screening programmes highlights the importance of continuous monitoring, as well as the need to promote quality improvement efforts, as recommended in the EU guidelines. The implementation of monitoring systems, ensuring availability of data for the entire process, together with initiatives aimed to enhance reproducibility of histology and quality of endoscopy, represent a priority in screening programmes management.

Even though the prevalence of smokers in Italy has decreased in the last thirty years (constant in the last decade), about 92.000 people die each year from tobacco-related disease, and causes a burden of disease of approximately 1,650,000 daly's each year. The International Agency for Research on Cancer (IARC) review of more than 100 econometric studies confirmed that tobacco taxes and consumption are strongly inversely related. In Italy an increase of 20 % of the tobacco prices (from 5 euro to 6 euro per pack) this would result in a prevalence of smoking reduction of 6.8% and a reduction of related diseases of 6%. Implementing a similar price-policy in Italy, could mean avoiding about 9,500 deaths and about 98.000 DALY's each year (in range period of 1-15 years). Using the amount of funding for the Italian National Health System in 2016, corresponding to about 111 billion euro, it is roughly estimated that the increase of one euro in the tobacco prices would save in terms of health costs about 600 million euro each year in Italy. Funding Statement : Research not funded

Introduction Limited information is available about outcomes of patients with malignant adenomas endoscopically resected at screening. The aim of the study was to evaluate diagnostic and therapeutic quality indicators and to correlate them with clinical and surgical outcomes. Materials and methods We reviewed endoscopic and histology characteristics of all pT1 tumours endoscopically removed at the time of colonoscopy assessment in subjects with a positive screening test result in the context of a population-based program. Results 392 pT1 tumours were completely removed by endoscopy (en-bloc = 86.7%, piecemeal = 13.3%) and the histology report was considered complete in 83.2% of cases. Treatment was limited to endoscopic excision for 120 patients (30.7%, Group 1), 272 (69.3%, Group 2) underwent radicalisation surgery. In patients who had at least 1 lymph node examined, the rate of nodal involvement was 5.4% (13/239); no metastatic node was found in the 21 (27.6%) out of 76 patients with low-risk adenomas, who underwent surgery. Conclusion Risk of nodal involvement in colorectal pT1 tumours is well predicted by known histologic features also in a screening setting, although it was lower than among patients from clinical series. Surgical overtreatment is still significantly present and there is ample room for improvement regarding diagnostic and therapeutic flow-chart.

Background & Aims Screening for colorectal cancer (CRC) with sigmoidoscopy reduces CRC incidence by detecting and removing adenomas. The number needed to screen is a measure of screening efficiency, but is not directly associated with adenoma removal. We propose the following 2 new metrics for quantifying the relationship between adenoma removal and CRC prevented: number of adenomas needed to remove (NNR) and adenoma dwell time avoided (DTA). Methods We collected data from 4 randomized trials of sigmoidoscopy screening (1 in the United States and 3 in Europe) to assess NNR and DTA. For each trial, NNR was computed as the number of adenomas removed from subjects in the intervention group, divided by the number of CRCs prevented. DTA was computed similarly but taking into account the timing of adenoma removal. Combined results across trials were assessed using standard meta-analytic techniques. Results The estimated NNR for the PLCO (Prostate, Lung, Colorectal and Ovarian) trial was 74 (95% confidence interval [CI], 56–110), for the NORCCAP (Norwegian Colorectal Cancer Prevention) trial was 71 (95% CI, 44–174), for the SCORE (Screening for Colon Rectum) trial was 27 (95% CI, 14–135), and for the UKFSST (UK Flexible Sigmoidoscopy Screening Trial) was 36 (95% CI, 28–52). The combined estimate (meta-analysis) of NNR was 52 (95% CI, 36–93) assuming heterogeneity (P for heterogeneity = .014). DTA estimates among trials ranged from 278 to 730 years, with a combined estimate of 500 (95% CI, 344–833) years assuming heterogeneity (P for heterogeneity = .035), or 2 CRC cases prevented per 1000 adenoma dwell years avoided. The combined estimates of NNR and DTA restricted to advanced adenomas were 13 (95% CI, 9–22) and 122 (95% CI, 90–190) years, respectively. Conclusions We collected data from 4 randomized trials of sigmoidoscopy screening for CRC to develop metrics of endoscopic efficiency, NNR and DTA, which are directly linked to adenoma detection and removal. They can be used to compare screening among endoscopic modalities and to more precisely measure adenoma to carcinoma transition rates.

The reductions in cancer morbidity and mortality afforded by population-based cancer screening programmes have led many low-income and middle-income countries to consider the implementation of national screening programmes in the public sector. Screening at the population level, when planned and organised, can greatly benefit the population, whilst disorganised screening can increase costs and reduce benefits. The International Cancer Screening Network (ICSN) was created to share lessons, experience, and evidence regarding cancer screening in countries with organised screening programmes. Organised screening programmes provide screening to an identifiable target population and use multidisciplinary delivery teams, coordinated clinical oversight committees, and regular review by a multidisciplinary evaluation board to maximise benefit to the target population. In this Series paper, we report outcomes of the first regional consultation of the ICSN held in Agartala, India (Sept 5-7, 2016), which included discussions from cancer screening programmes from Denmark, the Netherlands, USA, and Bangladesh. We outline six essential elements of population-based cancer screening programmes, and share recommendations from the meeting that policy makers might want to consider before implementation.

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.

The European Code Against Cancer is a set of recommendations to give advice on cancer prevention. Its 4th edition is an update of the 3rd edition, from 2003. Working Groups of independent experts from different fields of cancer prevention were appointed to review the recommendations, supported by a Literature Group to provide scientific and technical support in the assessment of the scientific evidence, through systematic reviews of the literature. Common procedures were developed to guide the experts in identifying, retrieving, assessing, interpreting and summarizing the scientific evidence in order to revise the recommendations. The Code strictly followed the concept of providing advice to European Union citizens based on the current best available science. The advice, if followed, would be expected to reduce cancer risk, referring both to avoiding or reducing exposure to carcinogenic agents or changing behaviour related to cancer risk and to participating in medical interventions able to avert specific cancers or their consequences. The information sources and procedures for the review of the scientific evidence are described here in detail. The 12 recommendations of the 4th edition of the European Code Against Cancer were ultimately approved by a Scientific Committee of leading European cancer and public health experts.\

In a project coordinated by the International Agency for Research on Cancer (IARC) 31 experts from 11 European countries and IARC have developed supplements to the current European guidelines for quality assurance in cervical cancer screening. The supplements take into account the potential of primary testing for human papillomavirus (HPV) and vaccination against HPV infection to improve cervical cancer prevention and control and will be published by the European Commission in book format. They include 62 recommendations or conclusions for which the strength of the evidence and the respective recommendations is graded. While acknowledging the available evidence for more efficacious screening using HPV primary testing compared to screening based on cytology, the authors and editors of the supplements emphasize that appropriate policy and programme organization remain essential to achieve an acceptable balance between benefit and harm of any screening or vaccination programme. A summary of the supplements and all of the graded recommendations are presented here in journal format to make key aspects of the updated and expanded guidelines known to a wider professional and scientific community. Keywords: Mass screening, Vaccination, Cervical neoplasms, Human papillomavirus, Evidence-based guidelines, Population-based programme

Colorectal cancer screening programmes in Italy invite 50-69-year-old residents for a faecal immunochemical test every two years, regardless of their citizenship.The 2013 National Survey on Italian colorectal cancer screening programmes compared immigrants born in low- or middle-income countries with subjects who were born in Italy, by collecting aggregated data on compliance, faecal immunochemical test results, compliance with colonoscopy, detected lesions and stage at diagnosis separately for Italians and immigrants.Overall, 85 screening programmes invited 3,292,451 subjects, of whom 192,629 had been born abroad (5.9%). Compliance with invitation was lower in immigrants (34.3% vs. 51.3% in Italians), with p0.001. Compliance was higher in females, regardless of the country of birth, in the youngest age group of immigrants but in the oldest of Italians. Immigrants showed a borderline excess of standardised faecal immunochemical test positivity rate at first screening (5.4% vs. 5.1% in Italians, p=0.05) and a significant excess at repeat screenings (4.8% vs. 4.4%, p=0.002). The detection rates for carcinoma and advanced adenomas were lower in immigrants than in Italians at first screening (respectively 1.34‰ vs. 1.62‰ and 8.41‰ vs. 9.25‰) - although the differences were not statistically significant - but not at repeat screening (respectively 1.06‰ vs. 0.98‰ and 6.90‰ vs. 6.79‰).Migrants showed a lower compliance with screening than Italians. The prevalence of neoplasia was lower at first screening and similar to the Italians' at repeat screenings.

Background: The EUROMED CANCER Network project aims to support non-EU Mediterranean countries in the development of cancer early detection and screening policies. Methods: Through a structured questionnaire information from 15 countries (Albania, Algeria, Bosnia and Herzegovina (BiH), Croatia, Egypt, Jordan, UN Interim Administration Mission in Kosovo, Lebanon, Montenegro, Morocco, Palestinian National Authority, Serbia, Syria, Tunisia and Turkey) were collected on cancer epidemiology and control. Results: Large differences between countries are evident. Breast cancer (BC) is the commonest cancer among women, though the incidence rate is much lower in non-EU than in EU Mediterranean countries. Conversely, cervical cancer (CC) is much more common in the former than in the latter countries. Colorectal cancer (CRC) is more frequent in Northern than in Eastern and Southern Mediterranean shores. Population-based cancer registries are available in few countries but most of them lack information on disease staging. Opportunistic screening for CC and BC is unevenly spread across and within countries; organised screening programmes are rare and do not meet international recommendations. BC and CC early detection is extensively considered a priority, while a few countries included CRC into their agenda. Conclusions: Collected data witnesses inadequacy of health information system and, in general, of the strategies for cancer control in the involved countries. A uniform approach for strengthening cancer control is not realistic neither feasible. Tailored preventive actions for cancer early detection have to be started concurrently with the development of a reliable health information system and, specifically, with cancer registration.

The International Agency for Research on Cancer (IARC) has updated its 2002 guidelines on screening for breast cancer, drawing on data from studies completed in the past 15 years.

Prezentujemy Panstwu tlumaczenie artykulu poświeconego organizacji skriningow populacyjnych. Grupa ekspertow uznanych w dziedzinie badan skriningowych zebrala i w syntetycznej formie przedstawila najwazniejsze warunki, ktorych spelnienie jest konieczne, aby mozna bylo mowic o dobrze funkcjonującym skriningu. Artykul wydaje nam sie na tyle cenny, ze postanowilyśmy przyblizyc go osobom, ktore są lub bedą wlączone w organizacje i realizacje skriningu w Polsce. Stanowi on rozwiniecie artykulu zatytulowanego Zalecenia komitetu ekspertow dzialającego w ramach projektu EuSANH dla Ministra Zdrowia w sprawie organizacji skriningow populacyjnych, opublikowanego w „Nowotwory Journal of Oncology” 2014, 64, 5. W celu ulatwienia realizacji populacyjnych programow badan przesiewowych w kierunku nowotworow podsumowano dotychczas zdobyte w Europie doświadczenia w tym zakresie. Wymieniono w punktach najwazniejsze kwestie, ktore obywatele, grupy rzecznikow, politycy, osoby organizujące opieke zdrowotną oraz pracownicy sluzby zdrowia powinni rozwazyc podczas planowania, realizacji i prowadzenia badan przesiewowych w kierunku raka. Lista jest na tyle ogolna, ze ma zastosowanie zarowno do skriningu raka piersi, jak i szyjki macicy oraz jelita grubego. Lista powstala na podstawie dowodow przedstawionych w trzech publikacjach Unii Europejskiej, zawierających wytyczne w sprawie kontroli jakości badan przesiewowych i diagnostyki raka. Dodatkowo zostala wzbogacona piś miennictwem oraz doświadczeniami ekspertow prezentowanymi w czasie warsztatu w ramach European Science Advisory Network . Realizacja programu badan przesiewowych w kierunku raka powinna byc podzielona na siedem etapow: 1) przygotowanie do planowania, 2) kompleksowe planowanie, 3) badanie wykonalności, 4) pilotaz i wdrozenie procesu, 5) rozwoj serwisu uslug skriningowych, 6) uruchomienie programu badan przesiewowych na duzą skale oraz 7) zapewnienie trwalości. O realizacji kazdego etapu mozna mowic jedynie wtedy, gdy zostanie spelniona określona liczba warunkow. Pomyślna realizacja programu badan przesiewowych wymaga akceptacji spolecznej oraz uzycia najlepszych praktyk opartych na dowodach i weryfi kacji adekwatności wykonania na kazdym etapie realizacji.

Purpose To compare the acceptability of computed tomographic (CT) colonography and flexible sigmoidoscopy (FS) screening and the factors predicting CT colonographic screening participation, targeting participants in a randomized screening trial. Materials and Methods Eligible individuals aged 58 years (n = 1984) living in Turin, Italy, were randomly assigned to be invited to screening for colorectal cancer with FS or CT colonography. After individuals who had died or moved away (n = 28) were excluded, 264 of 976 (27.0%) underwent screening with FS and 298 of 980 (30.4%) underwent CT colonography. All attendees and a sample of CT colonography nonattendees (n = 299) were contacted for a telephone interview 3-6 months after invitation for screening, and screening experience and factors affecting participation were investigated. Odds ratios (ORs) were computed by means of multivariable logistic regression. Results For the telephone interviews, 239 of 264 (90.6%) FS attendees, 237 of 298 (79.5%) CT colonography attendees, and 182 of 299 (60.9%) CT colonography nonattendees responded. The percentage of attendees who would recommend the test to friends or relatives was 99.1% among FS and 93.3% among CT colonography attendees. Discomfort associated with bowel preparation was higher among CT colonography than FS attendees (OR, 2.77; 95% confidence interval [CI]: 1.47, 5.24). CT colonography nonattendees were less likely to be men (OR, 0.36; 95% CI: 0.18, 0.71), retired (OR, 0.31; 95% CI: 0.13, 0.75), to report regular physical activity (OR, 0.37; 95% CI: 0.20, 0.70), or to have read the information leaflet (OR, 0.18; 95% CI: 0.08, 0.41). They were more likely to mention screening-related anxiety (mild: OR, 6.30; 95% CI: 2.48, 15.97; moderate or severe: OR, 3.63; 95% CI: 1.87, 7.04), erroneous beliefs about screening (OR, 32.15; 95% CI: 6.26, 165.19), or having undergone a recent fecal occult blood test (OR, 13.69; 95% CI: 3.66, 51.29). Conclusion CT colonography and FS screening are well accepted, but further reducing the discomfort from bowel preparation may increase CT colonography screening acceptability. Negative attitudes, erroneous beliefs about screening, and organizational barriers are limiting screening uptake; all these factors are modifiable and therefore potentially susceptible to interventions. © RSNA, 2017 Online supplemental material is available for this article.