Childhood and Adolescent Central Nervous System Tumours in Spain: Incidence and Survival over 20 Years: A Historical Baseline for Current Assessment.

BACKGROUND: Central nervous system (CNS) neoplasms are highly frequent solid tumours in children and adolescents. While some studies have shown a rise in their incidence in Europe, others have not. Survival remains limited. We addressed two questions about these tumours in Spain: (1) Is incidence increasing? and (2) Has survival improved? METHODS: This population-based study included 1635 children and 328 adolescents from 11 population-based cancer registries with International Classification of Childhood Cancer Group III tumours, incident in 1983-2007. Age-specific and age-standardised (world population) incidence rates (ASRws) were calculated. Incidence time trends were characterised using annual percent change (APC) obtained with Joinpoint. Cases from 1991 to 2005 (1171) were included in Kaplan-Meier survival analyses, and the results were evaluated with log-rank and log-rank for trend tests. Children's survival was age-standardised using: (1) the age distribution of cases and the corresponding trends assessed with Joinpoint; and (2) European weights for comparison with Europe. RESULTS: ASRw 1983-2007: children: 32.7 cases/106; adolescents: 23.5 cases/106. The overall incidence of all tumours increased across 1983-2007 in children and adolescents. Considering change points, the APCs were: (1) children: 1983-1993, 4.3%^ (1.1; 7.7); 1993-2007, -0.2% (-1.9; 1.6); (2) adolescents: 1983-2004: 2.9%^ (0.9; 4.9); 2004-2007: -7.7% (-40; 41.9). For malignant tumours, the trends were not significant. 5-year survival was 65% (1991-2005), with no significant trends (except for non-malignant tumours). CONCLUSIONS: CNS tumour incidence in Spain was found to be similar to that in Europe. Rises in incidence may be mostly attributable to changes in the registration of non-malignant tumours. The overall malignant CNS tumour trend was compatible with reports for Southern Europe. Survival was lower than in Europe, without improvement over time. We provide a baseline for assessing current paediatric oncology achievements and incidence in respect of childhood and adolescent CNS tumours.

Incidence and time trends of childhood hematological neoplasms: a 36-year population-based study in the southern European context, 1983-2018.

Background: Hematological neoplasms (HNs) are the first and most common childhood cancers globally. Currently, there is a lack of updated population-based data on the incidence of these cancers in the Spanish pediatric population. This study aimed to describe the incidence and incidence trends of HNs in children (0-14 years) in Spain using data from the Spanish Network of Cancer Registries and to compare the results with other southern European countries. Methods: Data were extracted from 15 Spanish population-based cancer registries between 1983 and 2018. Cases were coded according to the International Classification of Diseases for Oncology, third edition, first revision, and grouped according to the International Classification of Childhood Cancer, third edition. Crude rates (CRs), age-specific rates, and age-standardized incidence rates using the 2013 European population (ASRE) were calculated and expressed as cases per 1,000,000 child-years. Incidence trends and annual percentage changes (APCs) were estimated. Results: A total of 4,747 HNs were recorded (59.5% boys). Age distribution [n (%)] was as follows: <1 year, 266 (5.6%); 1-4 years, 1,726 (36.4%); 5-9 years, 1,442 (30.4%); and 10-14 years, 1,313 (27.6%). Leukemias were the most common group, with a CR and an ASRE of 44.0 (95%CI: 42.5; 45.5) and 44.1 (95%CI: 42.6; 45.7), respectively. The CR and ASRE of lymphomas were 20.1 (95%CI: 19.1; 21.1) and 20.0 (95%CI: 19.0; 21.1), respectively. The comparable incidence rates between our results and those of other southern European countries were similar for lymphomas, while some differences were observed for leukemias. From 1988 to 2016, the trend in leukemia incidence was stable for both sexes, with an APC of 0.0 (95%CI: -0.5; 0.7), whereas a constant overall increase was observed for lymphoma in both sexes, with an APC of 1.0 (95%CI: 0.4; 1.6). Conclusion: Leukemias are the most common HNs in children, and their incidence has remained stable since 1988, whereas the incidence of lymphomas has increased every year. Lymphoma incidence is like that of other southern European countries, while leukemia incidence is similar only to that of southwestern European countries. Collaborative cancer registry projects allow for assessing epidemiological indicators for cancers such as HNs, which helps health authorities and clinicians provide more knowledge about these malignancies.

The 2022 ENCR Recommendations on recording and reporting of urothelial tumours of the urinary tract.

An updated European Network of Cancer registries (ENCR) Recommendations on Recording and Reporting of Urothelial Tumours of the Urinary Tract had been published in 2022. After the publication by the ENCR of the "Recommendations for coding bladder cancers" in 1995, knowledge about the biology and pathology of urinary tract tumors and their classification has varied and increased substantially. On the other hand, several studies have shown that cancer registries use different definitions, criteria for inclusion and coding of urothelial tumors. This great variability among registries affects not only the criteria for recording (registration, coding and classification) but also the criteria of reporting (counting in the statistics of incidence and survival) urinary tract tumors. This causes difficulties in the data comparability from different registries. Recording and reporting of urothelial tumors requires the application of standard criteria that must take into account the combination of the multiple aspects as the primary topography, the histological type, the grade, the extent of invasion, the multi-centricity, the progressions and the time interval between tumors. This led to the creation of a Working Group of the ENCR that developed these recommendations on the recording and reporting of urothelial tumors of the urinary tract. This article reports these recommendations and the rationale for each.

Incidence and survival of lymphoid neoplasms in Spain, 2002-2013: A population-based study from the Spanish Network of Cancer Registries (REDECAN).

Introduction: The aim of this study was to describe incidence, incidence trends and survival patterns of lymphoid neoplasms (LNs) and its subtypes in Spain in the period 2002-2013 using data from the Spanish Network of Cancer Registries (REDECAN). Materials and Methods: Data were extracted from 13 Spanish population-based cancer registries. LNs incident cases were codified using the International Classification of Diseases for Oncology, third edition (ICD-O-3) and grouped according to the WHO 2008 classification. Age-standardized incidence rates to the 2013 European standard population (ASIRe) were obtained. Poisson regression models were used to analyze trends in incidence rates and estimate the annual percentage change (APC) for each subtype. The number of cases in Spain for 2023 was estimated by applying the estimated age-specific rates for the year 2023 to the 2023 Spanish population. Observed survival (OS) was estimated by the Kaplan-Meier method and net survival (NS) by the Pohar-Perme method. Sex- and age-specific estimates of 5-year NS were calculated, as well as its changes according to two periods of diagnosis (2002-2007 and 2008-2013). Results: LNs accounted for 69% (n=39,156) of all hematological malignancies (n=56,751) diagnosed during the period of study. Median age at diagnosis was 67 years (interquartile range (IQR) = 52-77). The overall ASIRe was 34.23 (95% confidence interval (CI): 33.89, 34.57) and showed a marked male predominance in almost all subtypes (global sex ratio = 1.45). During the study period, incidence trends of LNs remained stable (APC: 0.3; 95% CI: -0.1, 0.6), nevertheless some subtypes showed statistically significant variations, such as LNs NOS category (APC: -5.6; 95% CI: -6.8, -4.3). Around 17,926 new cases of LNs will be diagnosed in 2023 in Spain. Survival rates differed considerably across age-groups, while they were similar between men and women. Five- year NS was 62.81% (95% CI: 62.1, 63.52) for all LNs, and varied widely across LNs subtypes, ranging from 39.21% to 90.25%. NS for all LNs improved from the first period of diagnosis to the second one, being 61.57% (95% CI: 60.56, 62.61) in 2002-2007 and 64.17% (95% CI: 63.29, 65.07) in 2008-2013. Conclusions: This study presents the first complete and extensive population-based analysis of LNs incidence and survival in Spain. These population-based data provide relevant information to better understand the epidemiology of LNs in Southern Europe and it features some useful points for public health authorities and clinicians. However, additional improvements regarding the registration of these hematological neoplasms can be implemented.

Overall and stage-specific survival of patients with screen-detected colorectal cancer in European countries: A population-based study in 9 countries.

Background: An increasing proportion of colorectal cancers (CRCs) are detected through screening due to the availability of organised population-based programmes. We aimed to analyse survival probabilities of patients with screen-detected CRC in European countries. Methods: Data from CRC patients were obtained from 16 population-based cancer registries in nine European countries. We included patients with cancer diagnosed from the year organised CRC screening programmes were introduced until the most recent year with available data at the time of analysis, whose ages at diagnosis fell into the age groups targeted by screening. Patients were followed up with regards to vital status until 2016-2020 across the various countries. Overall and CRC-specific survival were analysed by mode of detection and stage at diagnosis for all countries combined and for each country separately using the Kaplan-Meier method. Findings: We included data from 228 134 patients, of whom 134 597 (aged 60-69 years at diagnosis targeted by screening in all countries) were considered in analyses for all countries combined. 22·3% (38 080/134 597) of patients had cancer detected through screening. Most screen-detected cancers were found at stages I-II (65·6% [12 772/19 469 included in stage-specific analyses]), while the majority of non-screen-detected cancers were found at stages III-IV (56·4% [31 882/56 543 included in stage-specific analyses]). Five-year overall and CRC-specific survival rates for patients with screen-detected cancer were 83·4% (95% CI 82·9-83·9) and 89·2% (88·8-89·7), respectively; for patients with non-screen-detected cancer, they were much lower (57·5% [57·2-57·8] and 65·7% [65·4-66·1], respectively). The favourable survival of patients with screen-detected cancer was also seen within each stage - five-year overall survival rates for patients with screen-detected stage I, II, III, and IV cancers were 92.4% (95% CI 91·6-93·1), 87·9% (86·6-89·1), 80·7% (79·3-82·0), and 32·3 (29·4-35·2), respectively. These patterns were also consistently seen for each individual country. Interpretation: Patients with cancer diagnosed at screening have a very favourable prognosis. In the rare case of detection of advanced stage cancer, survival probabilities are still much higher than those commonly reported for all patients regardless of mode of detection. Although these results cannot be taken to quantify screening effects, they provide useful and encouraging information for patients with screen-detected CRC and their physicians. Funding: This study was supported in part by grants from the German Federal Ministry of Education and Research and the German Cancer Aid.

Proportion and stage distribution of screen-detected and non-screen-detected colorectal cancer in nine European countries: an international, population-based study.

BACKGROUND: The effects of recently implemented colorectal cancer screening programmes in Europe on colorectal cancer mortality will take several years to be fully known. We aimed to analyse the characteristics and parameters of screening programmes, proportions of colorectal cancers detected through screening, and stage distribution in screen-detected and non-screen-detected colorectal cancers to provide a timely assessment of the potential effects of screening programmes in several European countries. METHODS: We conducted this population-based study in nine European countries for which data on mode of detection were available (Belgium, Denmark, England, France, Italy, Ireland, the Netherlands, Slovenia, and Spain). Data from 16 population-based cancer registries were included. Patients were included if they were diagnosed with colorectal cancer from the year that organised colorectal cancer screening programmes were implemented in each country until the latest year with available data at the time of analysis, and if their age at diagnosis fell within the age groups targeted by the programmes. Data collected included sex, age at diagnosis, date of diagnosis, topography, morphology, clinical and pathological TNM information based on the edition in place at time of diagnosis, and mode of detection (ie, screen detected or non-screen detected). If stage information was not available, patients were not included in stage-specific analyses. The primary outcome was proportion and stage distribution of screen-detected versus non-screen detected colorectal cancers. FINDINGS: 228 667 colorectal cancer cases were included in the analyses. Proportions of screen-detected cancers varied widely across countries and regions. The highest proportions (40-60%) were found in Slovenia and the Basque Country in Spain, where FIT-based programmes were fully rolled out, and participation rates were higher than 50%. A similar proportion of screen-detected cancers was also found for the Netherlands in 2015, where participation was over 70%, even though the programme had not yet been fully rolled out to all age groups. In most other countries and regions, proportions of screen-detected cancers were below 30%. Compared with non-screen-detected cancers, screen-detected cancers were much more often found in the distal colon (range 34·5-51·1% screen detected vs 26·4-35·7% non-screen detected) and less often in the proximal colon (19·5-29·9% screen detected vs 24·9-32·8% non-screen detected) p≤0·02 for each country, more often at stage I (35·7-52·7% screen detected vs 13·2-24·9% non-screen detected), and less often at stage IV (5·8-12·5% screen detected vs 22·5-31·9% non-screen detected) p<0·0001 for each country. INTERPRETATION: The proportion of colorectal cancer cases detected by screening varied widely between countries. However, in all countries, screen-detected cancers had a more favourable stage distribution than cancers detected otherwise. There is still much need and scope for improving early detection of cancer across all segments of the colorectum, and particularly in the proximal colon and rectum. FUNDING: Deutsche Krebshilfe.

Cancer Survival in Adults in Spain: A Population-Based Study of the Spanish Network of Cancer Registries (REDECAN).

The assessment of cancer survival at the population level is essential for monitoring progress in cancer control. We aimed to assess cancer survival and its trends in adults in Spain. Individual records of 601,250 adults with primary cancer diagnosed during 2002-2013 and followed up to 2015 were included from 13 population-based cancer registries. We estimated net survival up to five years after diagnosis and analyzed absolute changes between 2002-2007 and 2008-2013. Estimates were age-standardized. Analyses were performed for 29 cancer groups, by age and sex. Overall, age-standardized five-year net survival was higher in women (61.7%, 95% CI 61.4-62.1%) than in men (55.3%, 95% CI 55.0-55.6%), and ranged by cancer from 7.2% (pancreas) to 89.6% (prostate) in men, and from 10.0% (pancreas) to 93.1% (thyroid) in women in the last period. Survival declined with age, showing different patterns by cancer. Between both periods, age-standardized five-year net survival increased overall by 3.3% (95% CI 3.0-3.7%) in men and 2.5% (95% CI 2.0-3.0%) in women, and for most cancer groups. Improvements were greater in patients younger than 75 years than in older patients. Chronic myeloid leukemia and myeloma showed the largest increases. Among the most common malignancies, the greatest absolute increases in survival were observed for colon (5.0%, 95% CI 4.0-6.0%) and rectal cancers (4.5%, 95% CI 3.2-5.9%). Survival improved even for some cancers with poor prognosis (pancreas, esophagus, lung, liver, and brain cancer). Further investigation of possible sociodemographic inequalities is warranted. This study contributes to the evaluation of cancer control and health services' effectiveness.

Using population-based data to evaluate the impact of adherence to endocrine therapy on survival in breast cancer through the web-application BreCanSurvPred.

We show how the use and interpretation of population-based cancer survival indicators can help oncologists talk with breast cancer (BC) patients about the relationship between their prognosis and their adherence to endocrine therapy (ET). The study population comprised a population-based cohort of estrogen receptor positive BC patients (N = 1268) diagnosed in Girona and Tarragona (Northeastern Spain) and classified according to HER2 status (+ / -), stage at diagnosis (I/II/III) and five-year cumulative adherence rate (adherent > 80%; non-adherent ≤ 80%). Cox regression analysis was performed to identify significant prognostic factors for overall survival, whereas relative survival (RS) was used to estimate the crude probability of death due to BC (PBC). Stage and adherence to ET were the significant factors for predicting all-cause mortality. Compared to stage I, risk of death increased in stage II (hazard ratio [HR] 2.24, 95% confidence interval [CI]: 1.51-3.30) and stage III (HR 5.11, 95% CI 3.46-7.51), and it decreased with adherence to ET (HR 0.57, 95% CI 0.41-0.59). PBC differences were higher in non-adherent patients compared to adherent ones and increased across stages: stage I: 6.61% (95% CI 0.05-13.20); stage II: 9.77% (95% CI 0.59-19.01), and stage III: 22.31% (95% CI 6.34-38.45). The age-adjusted survival curves derived from this modeling were implemented in the web application BreCanSurvPred ( https://pdocomputation.snpstats.net/BreCanSurvPred ). Web applications like BreCanSurvPred can help oncologists discuss the consequences of non-adherence to prescribed ET with patients.

No Excess Mortality up to 10 Years in Early Stages of Breast Cancer in Women Adherent to Oral Endocrine Therapy: A Probabilistic Graphical Modeling Approach.

Breast cancer (BC) is globally the most frequent cancer in women. Adherence to endocrine therapy (ET) in hormone-receptor-positive BC patients is active and voluntary for the first five years after diagnosis. This study examines the impact of adherence to ET on 10-year excess mortality (EM) in patients diagnosed with Stages I to III BC (N = 2297). Since sample size is an issue for estimating age- and stage-specific survival indicators, we developed a method, ComSynSurData, for generating a large synthetic dataset (SynD) through probabilistic graphical modeling of the original cohort. We derived population-based survival indicators using a Bayesian relative survival model fitted to the SynD. Our modeling showed that hormone-receptor-positive BC patients diagnosed beyond 49 years of age at Stage I or beyond 59 years at Stage II do not have 10-year EM if they follow the prescribed ET regimen. This result calls for developing interventions to promote adherence to ET in patients with hormone receptor-positive BC and in turn improving cancer survival. The presented methodology here demonstrates the potential use of probabilistic graphical modeling for generating reliable synthetic datasets for validating population-based survival indicators when sample size is an issue.

Registration of Urothelial Tumours in Cancer Registries: How to Improve and Make It More Useful?

Due to the differences in the definition, criteria of inclusion and coding of urothelial tumours (UTs), data of different cancer registries (CRs) are not comparable. The aim of this work is to study current practices of registration of UT in the European CR of the GRELL countries in order to propose new registration rules to correctly describe incidence and survival of progressive tumours like UT. A questionnaire was sent to 91 CRs to assess whether non-invasive (NI)UT, multiple UTs, UTs occurring outside or before the operating period and time between UTs are currently considered in tumour recording and reporting. All participating CRs (n = 42) record a NI bladder UT in sole occurrence. In case of progressive bladder UT, 98% of the CRs record at least one NIUT but 19% don't record the invasive progression. 17% of the CRs don't record an invasive pelvic tumour that occurs after a NI bladder UT. 19% of the CRs don't record an invasive bladder UT that followed a NI tumour occurring outside the zone or period of time. The recording of two synchronous UTs is carried out with a grouping topography for 36% of the CRs. The same analysis conducted on the reporting of the incidence of UT also shows heterogeneity. We conclude that there is an urgent need to define clear rules for the registration of UT.

Predicting Ovarian-Cancer Burden in Catalonia by 2030: An Age-Period-Cohort Modelling.

Ovarian cancer is the most lethal gynaecological cancer in very-high-human-development-index regions. Ovarian cancer incidence and mortality rates are estimated to globally rise by 2035, although incidence and mortality rates depend on the region and prevalence of the associated risk factors. The aim of this study is to assess changes in incidence and mortality of ovarian cancer in Catalonia by 2030. Bayesian autoregressive age-period-cohort models were used to predict the burden of OC incidence and mortality rates for the 2015-2030 period. Incidence and mortality rates of ovarian cancer are expected to decline in Catalonia by 2030 in women ≥ 45 years of age. A decrease in ovarian-cancer risk was observed with increasing year of birth, with a rebound in women born in the 1980s. A decrease in mortality was observed for the period of diagnosis and period of death. Nevertheless, ovarian-cancer mortality remains higher among older women compared to other age groups. Our study summarizes the most plausible scenario for ovarian-cancer changes in terms of incidence and mortality in Catalonia by 2030, which may be of interest from a public health perspective for policy implementation.

Ten-Year Probabilities of Death Due to Cancer and Cardiovascular Disease among Breast Cancer Patients Diagnosed in North-Eastern Spain.

Mortality from cardiovascular disease (CVD), second tumours, and other causes is of clinical interest in the long-term follow-up of breast cancer (BC) patients. Using a cohort of BC patients (N = 6758) from the cancer registries of Girona and Tarragona (north-eastern Spain), we studied the 10-year probabilities of death due to BC, other cancers, and CVD according to stage at diagnosis and hormone receptor (HR) status. Among the non-BC causes of death (N = 720), CVD (N = 218) surpassed other cancers (N = 196). The BC cohort presented a significantly higher risk of death due to endometrial and ovarian cancers than the general population. In Stage I, HR- patients showed a 1.72-fold higher probability of all-cause death and a 6.11-fold higher probability of breast cancer death than HR+ patients. In Stages II-III, the probability of CVD death (range 3.11% to 3.86%) surpassed that of other cancers (range 0.54% to 3.11%). In Stage IV patients, the probability of death from any cancer drove the mortality risk. Promoting screening and preventive measures in BC patients are warranted, since long-term control should encompass early detection of second neoplasms, ruling out the possibility of late recurrence. In patients diagnosed in Stages II-III at an older age, surveillance for preventing late cardiotoxicity is crucial.

Trends in lung cancer incidence by age, sex and histology from 2012 to 2025 in Catalonia (Spain).

Lung cancer remains one the most common cancers in Europe and ranks first in terms of cancer mortality in both sexes. Incidence rates vary by region and depend above all on the prevalence of tobacco consumption. In this study we describe recent trends in lung cancer incidence by sex, age and histological type in Catalonia and project changes according to histology by 2025. Bayesian age-period-cohort models were used to predict trends in lung cancer incidence according to histological type from 2012 to 2025, using data from the population-based Catalan cancer registries. Data suggest a decrease in the absolute number of new cases in men under the age of 70 years and an increase in women aged 60 years or older. Adenocarcinoma was the most common type in both sexes, while squamous cell carcinoma and small cell carcinoma were decreasing significantly among men. In both sexes, the incident cases increased by 16% for patients over 70 years. Increases in adenocarcinoma and rising incidence in elderly patients suggest the need to prioritize strategies based on multidisciplinary teams, which should include geriatric specialists.

Prostate Cancer Survival by Risk and Other Prognostic Factors in Mallorca, Spain.

Studies about the survival of patients with prostate cancer by stage or risk of progression are scarce. The aims of this study were (1) to determine the cause-specific survival by risk in prostate cancer patients in Mallorca diagnosed in the period 2006-2011; (2) to identify the factors that explain and predict the likelihood of survival and the risk of dying from this type of cancer; and (3) to determine the distribution of prostate cancer by risk in the patients in Mallorca diagnosed in the period 2006-2011. Incident prostate cancer cases diagnosed between 2006 and 2011 were identified through the Mallorca Cancer Registry. We collected age; date and method of diagnosis; date of follow-up or death; T, N, M and stage according to the TNM 7th edition; Gleason score; prostate-specific antigen (PSA); histology according to the International Classification of Diseases for Oncology (ICD-O) 3rd edition, comorbidities and treatments. We calculated risk in four categories: low, medium, high and very high. The end point of follow-up was 31 December 2014. Multiple imputation (MI) was performed to estimate cases with unknown risk. We identified 2921 cases. Five years after diagnosis, survival after MI was 89% globally, and was 100% for low-risk cases, 96% for medium risk, 93% for high risk and 69% for very-high-risk cases. Cases with histology other than adenocarcinoma, with high (and especially very high) risk, as well as with systemic, mixed and observation/unspecified treatments had worse prognoses.

Variation of Cancer Incidence between and within GRELL Countries.

Variation in cancer incidence between countries and groups of countries has been well studied. However cancer incidence is linked to risk factors that may vary within countries, and may subsist in localized geographic areas. In this study we investigated between- and within-country variation in the incidence of all cancers combined for countries belonging to the Group for Cancer Epidemiology and Registration in Latin Language Countries (GRELL). We hypothesized that investigation at the micro-level (circumscribed regions and local cancer registry areas) would reveal incidence variations not evident at the macro level and allow identification of cancer incidence hotspots for research, public health, and to fight social inequalities. Data for all cancers diagnosed in 2008-2012 were extracted from Cancer Incidence in Five Continents, Vol XI. Incidence variation within a country or region was quantified as r/R, defined as the difference between the highest and lowest incidence rates for cancer registries within a country/region (r), divided by the incidence rate for the entire country/region × 100. We found that the area with the highest male incidence had an ASRw 4.3 times higher than the area with the lowest incidence. The area with the highest female incidence had an ASRw 3.3 times higher than the area with the lowest incidence. Areas with the highest male ASRws were Azores (Portugal), Florianopolis (Brazil), Metropolitan France, north Spain, Belgium, and north-west and north-east Italy. Areas with the highest female ASRws were Florianopolis (Brazil), Belgium, north-west Italy, north-east Italy, central Italy, Switzerland and Metropolitan France. Our analysis has shown that cancer incidence varies markedly across GRELL countries but also within several countries: the presence of several areas with high cancer incidence suggests the presence of area-specific risk factors that deserve further investigation.

Colorectal cancer incidence, mortality, and stage distribution in European countries in the colorectal cancer screening era: an international population-based study.

BACKGROUND: Colorectal cancer screening programmes and uptake vary substantially across Europe. We aimed to compare changes over time in colorectal cancer incidence, mortality, and stage distribution in relation to colorectal cancer screening implementation in European countries. METHODS: Data from nearly 3·1 million patients with colorectal cancer diagnosed from 2000 onwards (up to 2016 for most countries) were obtained from 21 European countries, and were used to analyse changes over time in age-standardised colorectal cancer incidence and stage distribution. The WHO mortality database was used to analyse changes over time in age-standardised colorectal cancer mortality over the same period for the 16 countries with nationwide data. Incidence rates were calculated for all sites of the colon and rectum combined, as well as the subsites proximal colon, distal colon, and rectum. Average annual percentage changes (AAPCs) in incidence and mortality were estimated and relevant patterns were descriptively analysed. FINDINGS: In countries with long-standing programmes of screening colonoscopy and faecal tests (ie, Austria, the Czech Republic, and Germany), colorectal cancer incidence decreased substantially over time, with AAPCs ranging from -2·5% (95% CI -2·8 to -2·2) to -1·6% (-2·0 to -1·2) in men and from -2·4% (-2·7 to -2·1) to -1·3% (-1·7 to -0·9) in women. In countries where screening programmes were implemented during the study period, age-standardised colorectal cancer incidence either remained stable or increased up to the year screening was implemented. AAPCs for these countries ranged from -0·2% (95% CI -1·4 to 1·0) to 1·5% (1·1 to 1·8) in men and from -0·5% (-1·7 to 0·6) to 1·2% (0·8 to 1·5) in women. Where high screening coverage and uptake were rapidly achieved (ie, Denmark, the Netherlands, and Slovenia), age-standardised incidence rates initially increased but then subsequently decreased. Conversely, colorectal cancer incidence increased in most countries where no large-scale screening programmes were available (eg, Bulgaria, Estonia, Norway, and Ukraine), with AAPCs ranging from 0·3% (95% CI 0·1 to 0·5) to 1·9% (1·2 to 2·6) in men and from 0·6% (0·4 to 0·8) to 1·1% (0·8 to 1·4) in women. The largest decreases in colorectal cancer mortality were seen in countries with long-standing screening programmes. INTERPRETATION: We observed divergent trends in colorectal cancer incidence, mortality, and stage distribution across European countries, which appear to be largely explained by different levels of colorectal cancer screening implementation. FUNDING: German Cancer Aid (Deutsche Krebshilfe) and the German Federal Ministry of Education and Research.

Skin melanoma deaths within 1 or 3 years from diagnosis in Europe.

The steep increase in incidence of cutaneous malignant melanoma in white populations mainly applies to thin lesions with good survival suggesting overdiagnosis. Based on population-based cancer registries (CRs), we have investigated changes in aggressive melanoma, selecting only cases who died within 1 or 3 years after diagnosis in 11 European countries between 1995 and 2012. Trends in fatal cases were analysed by period of diagnosis, sex, tumour thickness, histologic subtype of the lesion, tumour site and CR with a multivariate generalised linear mixed effects model, where geographical area was considered as a random effect. We collected data on 123 360 invasive melanomas, with 5133 fatal cases at 1 year (4%) and 12 330 (10%) at 3 years. The number of fatal cases showed a 16% decrease at 1 year and 8% at 3 years between the first (1995-2000) and the last (2007-2012) period. The highest proportion of fatal cases was seen for men, older age (≥65 years), thick lesions (>1 mm), nodular melanoma, melanoma on the trunk and for poorly documented cases, lacking information about thickness and histologic subtype. The mixed-effects model showed a remarkable variability among European countries. The majority of registries showed a decreasing trend in fatal cases, but a few registries showed an opposite pattern. Trends in fatal melanoma cases, highlighting real changes in risk not related to overdiagnosis, showed a decrease in most European countries, with a few exceptions. Stronger efforts for early detection could lead to a more efficient treatment of melanoma in general.

Predicting the rising incidence and mortality of endometrial cancers among women aged 65-74 years in Catalonia.

Endometrial cancer is currently one of the most common gynecological cancers. Reported incidence rates vary in Spain depending on the region. We estimated what the incidence and mortality of endometrial cancers in Catalonia will be by 2030 and compared the predictions with data from 2010. Bayesian autoregressive age-period-cohort models were employed to predict incidence and mortality rates for 2015-2030. The incidence of endometrial cancer for women younger than 65 years was predicted to be lower in 2030 than in 2010, whereas it was predicted to be higher for women aged 65-74 years. Moreover, mortality rates for women aged ≥65 in 2030 are likely to exceed the rates in 2010. Five-year relative survival for all ages was slightly higher in the period 2005-2009 (79.3 %, 95 %CI: 75.8 %-82.9 %) compared with those in 1995-1999 (76.0 %, 95 %CI: 72.1 %-80.2 %). This plausible new scenario might be useful to plan new clinical and preventive strategies in the near future.

Missing data imputation and synthetic data simulation through modeling graphical probabilistic dependencies between variables (ModGraProDep): An application to breast cancer survival.

BACKGROUND: Two common issues may arise in certain population-based breast cancer (BC) survival studies: I) missing values in a survivals' predictive variable, such as "Stage" at diagnosis, and II) small sample size due to "imbalance class problem" in certain subsets of patients, demanding data modeling/simulation methods. METHODS: We present a procedure, ModGraProDep, based on graphical modeling (GM) of a dataset to overcome these two issues. The performance of the models derived from ModGraProDep is compared with a set of frequently used classification and machine learning algorithms (Missing Data Problem) and with oversampling algorithms (Synthetic Data Simulation). For the Missing Data Problem we assessed two scenarios: missing completely at random (MCAR) and missing not at random (MNAR). Two validated BC datasets provided by the cancer registries of Girona and Tarragona (northeastern Spain) were used. RESULTS: In both MCAR and MNAR scenarios all models showed poorer prediction performance compared to three GM models: the saturated one (GM.SAT) and two with penalty factors on the partial likelihood (GM.K1 and GM.TEST). However, GM.SAT predictions could lead to non-reliable conclusions in BC survival analysis. Simulation of a "synthetic" dataset derived from GM.SAT could be the worst strategy, but the use of the remaining GMs models could be better than oversampling. CONCLUSION: Our results suggest the use of the GM-procedure presented for one-variable imputation/prediction of missing data and for simulating "synthetic" BC survival datasets. The "synthetic" datasets derived from GMs could be also used in clinical applications of cancer survival data such as predictive risk analysis.

Exceso de mortalidad en las pacientes con cáncer de mama en estadios precoces en Tarragona y Gerona (España) / Excess mortality among breast cancer patients in early stages in Tarragona and Gerona (Spain)

OBJETIVO: Analizar la supervivencia poblacional del cáncer de mama (CM) en estadios precoces, estimando la tendencia temporal del exceso de mortalidad (EM) a largo plazo en periodos anuales y quinquenales, y determinando, si es posible, una proporción de pacientes que puedan considerarse curadas. MÉTODO: Se incluyó la cohorte de pacientes diagnosticadas de CM en estadios I y II antes de los 60 años de edad en Gerona y Tarragona (N = 2453). Se calcularon la supervivencia observada (SO) y la supervivencia relativa (SR) al CM hasta los 20 años de seguimiento. Para valorar el EM se estimó la SR a intervalos anuales (SRI) y quinquenales (SR5). Los resultados se presentan por grupos de edad (≤49 y 50-59), estadio (I/II) y periodo de diagnóstico (1985-1994 y 1995-2004). RESULTADOS: En el estadio I, la SO y la SR fueron mayores en 1995-2004 que en 1985-1994: 3,5% a los 15 años de seguimiento y 4,5% a los 20 años. La SO superó el 80% en el estadio I y se mantuvo inferior al 70% en el estadio II. Sin embargo, el EM a largo plazo no desapareció (SRI <1) independientemente del grupo de edad, el estadio y el periodo de diagnóstico. A los 15 años de seguimiento, el EM a 5 años osciló entre el 1-5% en el estadio I (SR5 ≥0,95) y el 5-10% en el estadio II. CONCLUSIONES: En nuestra cohorte, a los 15 años de seguimiento se detectó que el EM anual no desapareció y el quinquenal fue del 1-10%. Por ello, no se pudo determinar una proporción de curación del CM durante el periodo de estudio

OBJECTIVE: To analyze the population-based survival of breast cancer (CM) diagnosed in early stages estimating the time trends of excess mortality (EM) in the long term in annual and five-year time intervals, and to determine, if possible, a proportion of patients who can be considered cured. METHOD: We included women diagnosed with BC under the age of 60 years in stages I and II in Girona and Tarragona (N = 2453). The observed (OS) and relative survival (RS) were calculated up to 20 years of follow-up. RS was also estimated at annual (RSI) and in five-year intervals (RS5) to graphically assess the EM. The results are presented by age groups (≤49 and 50-59), stage (I/II) and diagnostic period (1985-1994 and 1995-2004). RESULTS: In stage I, OS and RS were higher during 1995-2004 compared to 1985-1994: 3.5% at 15 years of follow-up and 4.5% at 20-years of follow-up. In 1995-2004, the OS surpassed 80% in stage I patients whereas in stage II it remained below 70%. During 1995-2004, the long-term EM did not level off towards 0 (RSI <1) independently of age group, stage and period of diagnosis. After 15 years of follow-up, the 5-year EM oscillated between 1 and 5% in stage I (RS5 ≥0.95) and between 5 and 10% in stage II. CONCLUSIONS: In our cohort, after 15 years of follow-up, it was detected that the annual EM did not disappear and the five-year EM remained between 1 and 10%. Therefore, it was not possible to determine a cure rate of BC during the study period