Population-level impact of the BMJ Rapid Recommendation for colorectal cancer screening: a microsimulation analysis.

OBJECTIVE: In 2019, a BMJ Rapid Recommendation advised against colorectal cancer (CRC) screening for adults with a predicted 15-year CRC risk below 3%. Using Switzerland as a case study, we estimated the population-level impact of this recommendation. DESIGN: We predicted the CRC risk of all respondents to the population-based Swiss Health Survey. We derived the distribution of risk-based screening start age, assuming predicted risk was calculated every 5 years between ages 25 and 70 and screening started when this risk exceeded 3%. Next, the MISCAN-Colon microsimulation model evaluated biennial faecal immunochemical test (FIT) screening with this risk-based start age. As a comparison, we simulated screening initiation based on age and sex. RESULTS: Starting screening only when predicted risk exceeded 3% meant 82% of women and 90% of men would not start screening before age 65 and 60, respectively. This would require 43%-57% fewer tests, result in 8%-16% fewer CRC deaths prevented and yield 19%-33% fewer lifeyears gained compared with screening from age 50. Screening women from age 65 and men from age 60 had a similar impact as screening only when predicted risk exceeded 3%. CONCLUSION: With the recommended risk prediction tool, the population impact of the BMJ Rapid Recommendation would be similar to screening initiation based on age and sex only. It would delay screening initiation by 10-15 years. Although halving the screening burdens, screening benefits would be reduced substantially compared with screening initiation at age 50. This suggests that the 3% risk threshold to start CRC screening might be too high.

A cohort analysis of residential radon exposure and melanoma incidence in Switzerland.

Radon is a radioactive noble gas found in Earth's crust. It accumulates in buildings, and accounts for approximately half the ionizing radiation dose received by humans. The skin is considerably exposed to ionizing radiation from radon. We aimed to evaluate the association between residential radon exposure and melanoma and squamous cell carcinoma incidence. The study included 1.3 million adults (20 years and older) from the Swiss National Cohort who were residents of the cantons of Vaud, Neuchâtel, Valais, Geneva, Fribourg, and Ticino at the study baseline (December 04, 2000). Cases of primary tumours of skin (melanoma and squamous cell carcinoma) were identified using data from cantonal cancer registries. Long-term residential radon and ambient solar ultraviolet radiation exposures were assigned to each individual's address at baseline. Cox proportional hazard models with age as time scale, adjusted for canton, socioeconomic position, demographic data available in the census, and outdoor occupation were applied. Total and age specific effects were calculated, in the full population and in non-movers, and potential effect modifiers were tested. In total 4937 incident cases of melanoma occurred during an average 8.9 years of follow-up. Across all ages, no increased risk of malignant melanoma or squamous cell carcinoma incidence in relation to residential radon was found. An association was only observed for melanoma incidence in the youngest age group of 20-29 year olds (1.68 [95% CI: 1.29, 2.19] 100 Bq/m3 radon). This association was mainly in women, and in those with low socio-economic position. Residential radon exposure might be a relevant risk factor for melanoma, especially for young adults. However, the results must be interpreted with caution as this finding is based on a relatively small number of melanoma cases. Accumulation of radon is preventable, and measures to reduce exposure and communicate the risks remain important to convey to the public.

Colorectal Cancer Screening Decision Based on Predicted Risk: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Incidence of and mortality from colorectal cancer (CRC) can be effectively reduced by screening with the fecal immunochemical test (FIT) or colonoscopy. Individual risk to develop CRC within 15 years varies from <1% to >15% among people aged 50 to 75 years. Communicating personalized CRC risk and appropriate screening recommendations could improve the risk-benefit balance of screening test allocations and optimize the use of limited colonoscopy resources. However, significant uncertainty exists regarding the feasibility and efficacy of risk-based screening. OBJECTIVE: We aim to study the effect of communicating individual CRC risk and a risk-based recommendation of the FIT or colonoscopy on participants' choice of screening test. We will also assess the feasibility of a larger clinical trial designed to evaluate the impact of personalized screening on clinical outcomes. METHODS: We will perform a pilot randomized controlled trial among 880 residents aged 50 to 69 years eligible to participate in the organized screening program of the Vaud canton, Switzerland. Participants will be recruited by mail by the Vaud CRC screening program. Primary and secondary outcomes will be self-assessed through questionnaires. The risk score will be calculated using the open-source QCancer calculator that was validated in the United Kingdom. Participants will be stratified into 3 groups-low (<3%), moderate (3% to <6%), and high (≥6%) risk-according to their 15-year CRC risk and randomized within each risk stratum. The intervention group participants will receive a newly designed brochure with their personalized risk and screening recommendations. The control group will receive the usual brochure of the Vaud CRC screening program. Our primary outcome, measured using a self-administered questionnaire, is appropriate screening uptake 6 months after the intervention. Screening will be defined as appropriate if participants at high risk undertake colonoscopy and participants at low risk undertake the FIT. We will also measure the acceptability of the risk score and screening recommendations and the psychological factors influencing screening behavior. We will also assess the feasibility of a full-scale randomized controlled trial. RESULTS: We expect that a total sample of 880 individuals will allow us to detect a difference of 10% (α=5%) between groups. The main outcome will be analyzed using a 2-tailed chi-squared test. We expect that appropriate screening uptake will be higher in the intervention group. No difference in overall screening uptake is expected. CONCLUSIONS: We will test the impact of personalized risk information and screening recommendations on participants' choice of screening test in an organized screening program. This study should advance our understanding of the feasibility of large-scale risk-based CRC screening. Our results may provide insights into the optimization of CRC screening by offering screening options with a better risk-benefit balance and optimizing the use of resources. TRIAL REGISTRATION: ClinicalTrials.gov NCT05357508; https://www.clinicaltrials.gov/study/NCT05357508. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/46865.

Breast cancer and occupation: Non-parametric and parametric net survival analyses among Swiss women (1990-2014).

Introduction: Occupation can contribute to differences in risk and stage at diagnosis of breast cancer. This study aimed at determining whether occupation, along with skill level and the socio-professional category, affect the breast cancer survival (BCS) up to 10 years after diagnosis. Materials and methods: We used cancer registry records to identify women diagnosed with primary invasive breast cancer in western Switzerland over the period 1990-2014 and matched them with the Swiss National Cohort. The effect of work-related variables on BCS was assessed using non-parametric and parametric net survival methods. Results: Study sample included 8,678 women. In the non-parametric analysis, we observed a statistically significant effect of all work-related variables on BCS. Women in elementary occupations, with low skill level, and in paid employment not classified elsewhere, had the lowest BCS, while professionals, those with the highest skill level and belonging to top management and independent profession category had the highest BCS. The parametric analysis confirmed this pattern. Considering elementary occupations as reference, all occupations but Craft and related trades had a hazard ratio (HR) below 1. Among professionals, technicians and associate professionals, and clerks, the protective effect of occupation was statistically significant and remained unchanged after adjustment for age, calendar period, registry, nationality, and histological type. After adjusting for tumor stage, the HRs increased only slightly, though turned non-significant. The same effect was observed in top management and independent professions and supervisors, low level management and skilled laborers, compared to unskilled employees. Conclusion: These results suggest that work-related factors may affect BCS. Yet, this study was conducted using a limited set of covariates and a relatively small study sample. Therefore, further larger studies are needed for more detailed analyses of at risk occupations and working conditions and assessing the potential interaction between work-related variables and tumor stage.

Comparison of statistical models to predict age-standardized cancer incidence in Switzerland.

This study compares the performance of statistical methods for predicting age-standardized cancer incidence, including Poisson generalized linear models, age-period-cohort (APC) and Bayesian age-period-cohort (BAPC) models, autoregressive integrated moving average (ARIMA) time series, and simple linear models. The methods are evaluated via leave-future-out cross-validation, and performance is assessed using the normalized root mean square error, interval score, and coverage of prediction intervals. Methods were applied to cancer incidence from the three Swiss cancer registries of Geneva, Neuchatel, and Vaud combined, considering the five most frequent cancer sites: breast, colorectal, lung, prostate, and skin melanoma and bringing all other sites together in a final group. Best overall performance was achieved by ARIMA models, followed by linear regression models. Prediction methods based on model selection using the Akaike information criterion resulted in overfitting. The widely used APC and BAPC models were found to be suboptimal for prediction, particularly in the case of a trend reversal in incidence, as it was observed for prostate cancer. In general, we do not recommend predicting cancer incidence for periods far into the future but rather updating predictions regularly.

Estimating 10-year risk of lung and breast cancer by occupation in Switzerland.

Introduction: Lung and breast cancer are important in the working-age population both in terms of incidence and costs. The study aims were to estimate the 10-year risk of lung and breast cancer by occupation and smoking status and to create easy to use age-, and sex-specific 10-year risk charts. Methods: New lung and breast cancer cases between 2010 and 2014 from all 5 cancer registries of Western Switzerland, matched with the Swiss National Cohort were used. The 10-year risks of lung and breast cancer by occupational category were estimated. For lung cancer, estimates were additionally stratified by smoking status using data on smoking prevalence from the 2007 Swiss Health Survey. Results: The risks of lung and breast cancer increased with age and were the highest for current smokers. Men in elementary professions had a higher 10-year risk of developing lung cancer compared to men in intermediate and managerial professions. Women in intermediate professions had a higher 10-year risk of developing lung cancer compared to elementary and managerial professions. However, women in managerial professions had the highest risk of developing breast cancer. Discussion: The 10-year risk of lung and breast cancer differs substantially between occupational categories. Smoking creates greater changes in 10-year risk than occupation for both sexes. The 10-year risk is interesting for both patients and professionals to inform choices related to cancer risk, such as screening and health behaviors. The risk charts can also be used as public health indicators and to inform policies to protect workers.

Colorectal cancer testing rates after implementation of an organised screening programme in Vaud, Switzerland.

AIMS OF THE STUDY: Canton Vaud, Switzerland, implemented an organised colorectal cancer  screening programme with colonoscopy and faecal occult blood tests in 2015, 4 to 6 years ahead of neighbouring cantons. Before its implementation, nearly half of Swiss citizens were already up to date with screening, primarily from opportunistic colonoscopies. We hypothesised that earlier implementation of an organised programme would be associated with greater increases in colorectal cancer testing rates. METHODS: We analysed Swiss health insurance claim data from CSS, a Swiss health insurer covering 16% of the Swiss population and 10% of canton Vaud. We stratified 50-69-year-olds into groups from Vaud, its four neighbouring cantons (Fribourg, Geneva, Neuchâtel and Valais), and the rest of Switzerland. We analysed overall, faecal occult blood test and colonoscopy testing rates for each year between 2010 and 2018. RESULTS: The overall testing rate increased from 7.6% in 2010 to 11.6% in 2018 (+4.0%) in Vaud, from 6.1% to 9.3% (+3.2%) in neighbouring cantons and from 7.4% to 8.6% (+1.2%) in the rest of Switzerland. The faecal occult blood test rate increased between 2016 and 2018 from 2.9% to 4.1% (+1.2%) in Vaud and from 1.7% to 2.6% (+0.9%) in neighbouring cantons, but it decreased from 3.1% to 1.5% (-1.6%) in the rest of Switzerland. The colonoscopy rate increased in all cantons, from 4.7% to 7.5% in Vaud (+2.8%), from 4.4% to 6.7% in neighbouring cantons (+2.3%) and from 4.3% to 7.1% in the rest of Switzerland (+2.8%). By 2018, 40% of faecal occult blood tests and 26% of colonoscopies in Vaud occurred in the organised programme. Those who completed an faecal occult blood test within the Vaud programme were younger, had fewer comorbidities and were more likely to have a high-deductible health plan than those tested outside the programme. CONCLUSIONS: Colorectal cancer testing rates increased between 2010 and 2018, with greater absolute increases in Vaud than in neighbouring cantons or the rest of Switzerland. Faecal occult blood test use increased in both Vaud and neighbouring cantons, possibly reflecting changes in testing patterns by general practitioners. By 2018, 40% of colonoscopies and 26% of faecal occult blood tests occurred within the screening programme.

Association between the colorectal cancer screening status of primary care physicians and their patients: Evidence from the Swiss Sentinella practice-based research network.

Swiss health insurance reimburses screening for colorectal cancer (CRC) with either colonoscopy or fecal occult blood test (FOBT). Studies have documented the association between a physician's personal preventive health practices and the practices they recommend to their patients. We explored the association between CRC testing status of primary care physicians (PCP) and the testing rate among their patients. From May 2017 to September 2017, we invited 129 PCP who belonged to the Swiss Sentinella Network to disclose their CRC test status and whether they had been tested with colonoscopy or FOBT/other methods. Each participating PCP collected demographic data and CRC testing status from 40 consecutive 50- to 75-year-old patients. We analyzed data from 69 (54%) PCP 50 years or older and 2623 patients. Most PCP were men (81%); 75% were tested for CRC (67% with colonoscopy and 9% with FOBT). Mean patient age was 63; 50% were women; 43% had been tested for CRC (38%, 1000/2623 with colonoscopy and 5%, 131/2623, with FOBT or other non-endoscopic test). In multivariate adjusted regression models that clustered patients by PCP, the proportion of patients tested for CRC was higher among PCP tested for CRC than among PCP not tested (47% vs 32%; OR 1.97; 95% CI 1.36 to 2.85). Since PCP CRC testing status is associated with their patients CRC testing rates, it informs future interventions that will alert PCPs to the influence of their health decisions and motivate them to further incorporate the values and preferences of their patients in their practice.

Global survival trends for brain tumors, by histology: analysis of individual records for 556,237 adults diagnosed in 59 countries during 2000-2014 (CONCORD-3).

BACKGROUND: Survival is a key metric of the effectiveness of a health system in managing cancer. We set out to provide a comprehensive examination of worldwide variation and trends in survival from brain tumors in adults, by histology. METHODS: We analyzed individual data for adults (15-99 years) diagnosed with a brain tumor (ICD-O-3 topography code C71) during 2000-2014, regardless of tumor behavior. Data underwent a 3-phase quality control as part of CONCORD-3. We estimated net survival for 11 histology groups, using the unbiased nonparametric Pohar Perme estimator. RESULTS: The study included 556,237 adults. In 2010-2014, the global range in age-standardized 5-year net survival for the most common sub-types was broad: in the range 20%-38% for diffuse and anaplastic astrocytoma, from 4% to 17% for glioblastoma, and between 32% and 69% for oligodendroglioma. For patients with glioblastoma, the largest gains in survival occurred between 2000-2004 and 2005-2009. These improvements were more noticeable among adults diagnosed aged 40-70 years than among younger adults. CONCLUSIONS: To the best of our knowledge, this study provides the largest account to date of global trends in population-based survival for brain tumors by histology in adults. We have highlighted remarkable gains in 5-year survival from glioblastoma since 2005, providing large-scale empirical evidence on the uptake of chemoradiation at population level. Worldwide, survival improvements have been extensive, but some countries still lag behind. Our findings may help clinicians involved in national and international tumor pathway boards to promote initiatives aimed at more extensive implementation of clinical guidelines.

[First epidemiological evaluation of the Vaud colorectal cancer screening program]. / Premier bilan du programme vaudois de dépistage du cancer colorectal.

The Vaud colorectal cancer (CRC) screening program, pioneer in Switzerland, offers since 2015 the choice between a biennial fecal immunological test (FIT) and a colonoscopy every 10 years to those aged 50 to 69. This first epidemiological evaluation of a Swiss CRC screening program shows an increasing uptake over the years and an equal distribution of choice of tests, but with regional differences. Quality of both FIT and colonoscopy fulfil the European norms. The high proportion of early-stage cancers (60% stage I) met expectations. The large increase in screening tests and limited colonoscopy capacity is leading to interprofessional discussions on strategies for prioritizing FIT, accompanied by additional orientation tools within the program and public sensitization, and for reducing the time taken to perform FIT positive colonoscopies.

Cet article résume les résultats de la première évaluation du programme vaudois de dépistage du cancer colorectal, réalisée selon des normes internationales. Ce programme, pionnier en Suisse, propose depuis 2015 le choix entre un test de détection de sang occulte dans les selles (FIT), tous les 2 ans, et une coloscopie, tous les 10 ans, aux personnes de 50 à 69 ans. La participation croît, avec un choix équilibré entre les 2 tests. Il existe cependant des différences régionales. La qualité des coloscopies et des FIT et la sécurité de réalisation des coloscopies sont conformes aux exigences. La forte proportion de cancers dépistés au stade précoce (60 % stade I) répond aux attentes. La forte croissance des dépistages et la capacité limitée en coloscopie mènent à des réflexions interprofessionnelles de stratégies de priorisation du FIT et de réduction des délais de réalisation des coloscopies sur FIT positif.

Work-Related Factors and Lung Cancer Survival: A Population-Based Study in Switzerland (1990-2014).

While previous Swiss studies have demonstrated differences in lung cancer mortality between occupational groups, no estimates are available on the association of occupation-related factors with lung cancer survival. This study aimed at determining whether occupation or work-related factors after diagnosis affect lung cancer survival. We used cancer registry records to identify lung cancer patients diagnosed between 1990 and 2014 in western Switzerland (n = 5773) matched with the Swiss National Cohort. The effect of occupation, the skill level required for the occupation, and the socio-professional category on 5-year lung cancer survival was assessed using non-parametric and parametric methods, controlling for histological type and tumour stage. We found that the net survival varied across skill levels and that the lowest skill level was associated with worse survival in both men and women. In the parametric models with minimal adjustment, we identified several occupational groups at higher risk of mortality compared to the reference category, particularly among men. After adjustment for histological type of lung cancer and tumour stage at diagnosis, most hazard ratios remained higher than 1, though non-statistically significant. Compared to top managers and self-employed workers, workers in paid employment without specific information on occupation were identified as the most at-risk socio-professional category in nearly all models. As this study was conducted using a relatively small sample and limited set of covariates, further studies are required, taking into account smoking habits and administrated cancer treatments. Information on return to work and working conditions before and after lung cancer diagnosis will also be highly valuable for analysing their effect on net lung cancer survival in large nationwide or international studies. Such studies are essential for informing health and social protection systems, which should guarantee appropriate work conditions for cancer survivors, beneficial for their quality of life and survival.

A prospective cohort analysis of residential radon and UV exposures and malignant melanoma mortality in the Swiss population.

BACKGROUND: Radon is a radioactive noble gas naturally found in the earth crust that can accumulate in buildings. In addition to lung cancer, alpha particles emitted by radon may contribute to the risk of skin cancer. We evaluated the association between residential radon exposure and skin cancer mortality, over a fifteen year period, taking residential ultra-violet (UV) exposure into account. METHODS: We included 4.9 million adults from the Swiss National Cohort. Hazard ratios for melanoma mortality were estimated using Cox proportional hazard models (20+ years old; follow-up 2001-2015). Long-term modelled residential radon and ambient UV exposures were assigned at baseline, and included together in the Cox models. With age as a time scale, models were adjusted for calendar time, sex, marital status, education, mother tongue, socioeconomic position, and occupational environment with potential for UV exposure. Age specific hazard ratios were derived. Effect modification, sensitivity analyses and the shape of the exposure response, as well as secondary analysis using other outcome definitions, were investigated. RESULTS: During follow-up (average of 13.6 years), 3,979 melanoma deaths were observed. Associations declined with age, with an adjusted hazard ratio per 100 Bq/m3 radon at age 60 of 1.10 (95% CI: 0.99, 1.23). The dose-response showed an approximate linear trend between the minimum and mean radon exposure of 75 Bq/m3. Having outdoor occupation significantly increased the risk of melanoma mortality associated with UV exposure compared to indoor jobs. Analysis restricted to the last five years of follow-up showed similar results compared to the main analysis. Similar associations were found for mortality from melanoma and non-melanoma skin cancer combined. CONCLUSION: With double the follow-up time, this study confirmed the previously observed association between residential radon exposure and melanoma and non-melanoma skin cancer mortality in Switzerland. Accumulation of radon indoors is preventable and of public health importance.

Occupational Factors and Socioeconomic Differences in Breast Cancer Risk and Stage at Diagnosis in Swiss Working Women.

Socioeconomic differences in breast cancer (BC) incidence are driven by differences in lifestyle, healthcare use and occupational exposure. Women of high socioeconomic status (SES) have a higher risk of BC, which is diagnosed at an earlier stage, than in low SES women. As the respective effects of occupation and SES remain unclear, we examined the relationships between occupation-related variables and BC incidence and stage when considering SES. Female residents of western Switzerland aged 18−65 years in the 1990 or 2000 census, with known occupation, were linked with records of five cancer registries to identify all primary invasive BC diagnosed between 1990 and 2014 in this region. Standardized incidence ratios (SIRs) were computed by occupation using general female population incidence rates, with correction for multiple comparisons. Associations between occupation factors and BC incidence and stage at diagnosis were analysed by negative binomial and multinomial logistic regression models, respectively. The cohort included 381,873 women-years and 8818 malignant BC, with a mean follow-up of 14.7 years. Compared with reference, three occupational groups predominantly associated with a high socioprofessional status had SIRs > 1: legal professionals (SIR = 1.68, 95%CI: 1.27−2.23), social science workers (SIR = 1.29; 95%CI: 1.12−1.49) and some office workers (SIR = 1.14; 95%CI: 1.09−1.20). Conversely, building caretakers and cleaners had a reduced incidence of BC (SIR = 0.69, 95%CI: 0.59−0.81). Gradients in BC risk with skill and socioprofessional levels persisted when accounting for SES. A higher incidence was generally associated with a higher probability of an early-stage BC. Occupation and SES may both contribute to differences in risk and stage at diagnosis of BC.

Change in colorectal cancer (CRC) testing rates associated with the introduction of the first organized screening program in canton Uri, Switzerland: Evidence from insurance claims data analyses from 2010 to 2018.

The first canton in Switzerland to implement an organized colorectal cancer screening program (OSP) was Uri. Starting in 2013, it offered 50-69-year-olds free testing with colonoscopy every 10 years or fecal occult blood test (FOBT) every 2 years. We tested the association between the OSP and testing rates over time. We analyzed claims data of 50-69-year-olds from Uri and neighboring cantons (NB) provided by a large health insurance and complemented it with data from the OSP. We fitted multivariate adjusted logistic regression models to compare overall testing rates and by method (colonoscopy or FOBT/both) We computed the 2018 rate of the population up-to-date with testing (colonoscopy within 9 years/FOBT within 2 years). Yearly overall testing rates in Uri increased from 8.7% in 2010 to 10.8% in 2018 and from 6.5% to 7.9% in NB. In Uri, the proportion tested with FOBT/both increased from 4.7% to 6.0% but decreased from 2.8% to 1.1% in NB. Testing by FOBT/both increased more between 2015 and 2018 than 2010-2012 in Uri than in NB (OR:2.1[95%CI:1.8-2.4]), it increased less for colonoscopy (OR:0.60[95%CI:0.51-0.70]), with no change in overall CRC testing (OR:0.91[95%CI:0.81-1.02]). In 2018 in Uri, 42.5% were up-to-date with testing (FOBT/both:9.2%, colonoscopy:35.7%); in NBs, 40.7% (FOBT/both:2.7%, colonoscopy:39%). Yearly FOBT rates in Uri were always higher than in NB. Though the OSP in Uri was not associated with a greater increase in overall testing rates, the OSP was associated with increased FOBT.

Ten-year changes in colorectal cancer screening in Switzerland: The Swiss Health Interview Survey 2007, 2012 and 2017.

Recent recommendations for colorectal cancer (CRC) screening suggest fecal occult blood test (FOBT) or colonoscopy. Since 2013, mandatory health insurance in Switzerland reimburse CRC screening. We set out to determine if CRC testing rate and type of CRC screening changed in Switzerland from 2007 to 2017 and between the three main language regions. We extracted data on 50-75-year-olds from the Swiss Health Interview Survey (SHIS) 2007, 2012 and 2017 to determine rates of self-reported testing with FOBT within last 2 years and colonoscopy within last 10 years. We estimated prevalence ratio (PR) in multivariate-adjusted logistic regression models and compared rates in German-, French- and Italian-speaking regions, adjusting for sociodemographic, self-rated health and insurance variables. Overall testing rates (FOBT or colonoscopy) increased in all regions from 2007 to 2017 (German-speaking 33.6% to 48.3%; French-speaking 30.8% to 48.8%; Italian-speaking 37.9% to 46.8%), mainly because of an increase in colonoscopy rate for screening reasons (p < 0.001 in all regions). Rates of FOBT testing fell significantly in the German-speaking region (11.9% to 4.4%, p < 0.001), but not in the Italian- (13.9% to 8.5%, p = 0.052) and French-speaking regions (7.6% to 7.4%, p = 0.138). Overall CRC testing rate rose from 33.2% in 2007 to 48.4% in 2017, mainly because of an increase of colonoscopy rate for screening reasons. Coverage remains below the 65% target of European guidelines. Organized screening programs encouraging FOBT screening could contribute to further increasing the CRC testing rate.

Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000-14 (CONCORD-3): analysis of individual data from 258 cancer registries in 61 countries.

BACKGROUND: Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS: We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS: 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION: This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING: Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

Management and Outcome of Young Women (≤40 Years) with Breast Cancer in Switzerland.

Background: An increase in breast cancer (BC) incidence in young women (YW) as well as disparities in BC outcomes have been reported in Switzerland. We sought to evaluate treatment and outcome differences among YW with BC (YWBC). Methods: YW diagnosed with stage I-III BC between 2000−2014 were identified through nine cancer registries. Concordance with international guidelines was assessed for 12 items covering clinical/surgical management, combined in a quality-of-care score. We compared score and survival outcome between the two linguistic-geographic regions of Switzerland (Swiss-Latin and Swiss-German) and evaluated the impact of quality-of-care on survival. Results: A total of 2477 women were included. The median age was 37.3 years (IQR 34.0−39.4 years), with 50.3% having stage II BC and 70.3% having estrogen receptor positive tumors. The mean quality-of-care score was higher in the Latin region compared to the German region (86.0% vs. 83.2%, p < 0.0005). Similarly, 5- and 10-year overall survival rates were higher in the Latin compared to the German region (92.3% vs. 90.2%, p = 0.0593, and 84.3% vs. 81.5%, p = 0.0025, respectively). There was no difference in survival according to the score. In the univariate analysis, women in the Latin region had a 28% lower mortality risk compared to women in the German region (hazard ratio 0.72; 95% CI 0.59−0.89). In the multivariable analysis, only stage, differentiation, tumor subtype and treatment period remained independently associated with survival. Conclusions: We identified geographic disparities in the treatment and outcome of YWBC in Switzerland. National guidelines for YWBC should be implemented to standardize treatment. Awareness should be raised among YW and clinicians that BC does not discriminate by age.

Does the morphology of cutaneous melanoma help to explain the international differences in survival? Results from 1 578 482 adults diagnosed during 2000-2014 in 59 countries (CONCORD-3).

BACKGROUND: CONCORD-3 highlighted wide disparities in population-based 5-year net survival for cutaneous melanoma during 2000-2014. Clinical evidence suggests marked international differences in the proportion of lethal acral and nodular subtypes of cutaneous melanoma. OBJECTIVES: We aimed to assess whether the differences in morphology may explain global variation in survival. METHODS: Patients with melanoma were grouped into the following seven morphological categories: malignant melanoma, not otherwise specified (International Classification of Diseases for Oncology, third revision morphology code 8720), superficial spreading melanoma (8743), lentigo maligna melanoma (8742), nodular melanoma (8721), acral lentiginous melanoma (8744), desmoplastic melanoma (8745) and other morphologies (8722-8723, 8726-8727, 8730, 8740-8741, 8746, 8761, 8770-8774, 8780). We estimated net survival using the nonparametric Pohar Perme estimator, correcting for background mortality by single year of age, sex and calendar year in each country or region. All-ages survival estimates were standardized using the International Cancer Survival Standard weights. We fitted a flexible parametric model to estimate the effect of morphology on the hazard of death. RESULTS: Worldwide, the proportion of nodular melanoma ranged between 7% and 13%. Acral lentiginous melanoma accounted for less than 2% of all registrations but was more common in Asia (6%) and Central and South America (7%). Overall, 36% of tumours were classified as superficial spreading melanoma. During 2010-2014, age-standardized 5-year net survival for superficial spreading melanoma was 95% or higher in Oceania, North America and most European countries, but was only 71% in Taiwan. Survival for acral lentiginous melanoma ranged between 66% and 95%. Nodular melanoma had the poorest prognosis in all countries. The multivariable analysis of data from registries with complete information on stage and morphology found that sex, age and stage at diagnosis only partially explain the higher risk of death for nodular and acral lentiginous subtypes. CONCLUSIONS: This study provides the broadest picture of distribution and population-based survival trends for the main morphological subtypes of cutaneous melanoma in 59 countries. The poorer prognosis for nodular and acral lentiginous melanomas, more frequent in Asia and Latin America, suggests the need for health policies aimed at specific populations to improve awareness, early diagnosis and access to treatment. What is already known about this topic? The histopathological features of cutaneous melanoma vary markedly worldwide. The proportion of melanomas with the more aggressive acral lentiginous or nodular histological subtypes is higher in populations with predominantly dark skin than in populations with predominantly fair skin. What does this study add? We aimed to assess the extent to which these differences in morphology may explain international variation in survival when all histological subtypes are combined. This study provides, for the first time, international comparisons of population-based survival at 5 years for the main histological subtypes of melanoma for over 1.5 million adults diagnosed during 2000-2014. This study highlights the less favourable distribution of histological subtypes in Asia and Central and South America, and the poorer prognosis for nodular and acral lentiginous melanomas. We found that later stage at diagnosis does not fully explain the higher excess risk of death for nodular and acral lentiginous melanoma compared with superficial spreading melanoma.

Research on occupational diseases in the absence of occupational data: a mixed-method study among cancer registries of Western Switzerland.

The contribution of occupation-related diseases to the global burden of disease is greatly underestimated, mainly due to a shortage of occupational exposure data. This problem is particularly salient in Switzerland, where no estimates of occupation-related disease burden exist, even for the well-recognised occupational cancers, such as malignant pleural mesothelioma and lung cancer. To overcome this situation, we launched a research project "Examining Cancers and Labour Indicators to assess the Burden" (ExCaLIBur). Within this project, we aimed to assess the need for and quality (i.e., completeness, accuracy and precision) of occupation registration in all cancer registries of Western Switzerland. We also aimed to find a relevant and feasible strategy to collect this information in the future. We applied a mixed research method. We observed that, independently of the level of precision (5-3-2-1-digit aggregation level), the accuracy was lesser in the registries that were able to actively search and verify occupational information. Overall, the distinction of occupations based on the 3-digit code presents an acceptable compromise in terms of precision. Having such occupations registered in all, or most, Swiss cancer registries routinely would obviously be valuable for epidemiological surveillance of occupational cancers in Switzerland. However, it seems less obvious how these data could fulfill the research objectives, since a better precision than 3-digit occupational coding is challenging to achieve. Currently, the collection of occupational data by the Swiss cancer registries remains feasible in the frame of specific research projects on occupational cancers. However, available data sources, as well as lack of financial and human resources, will continue to affect quality of the collected occupation data. Therefore, the usage of the standardised questionnaire retracing the individual occupational history to enable further assessment of individual exposure to potential occupational hazards is recommended. However, this approach will disable the Swiss registries to insuring their epidemiological surveillance mission with respect to occupational cancers in Switzerland, for which national statistics remain limited.