Jan Willem Coebergh

Cancer incidence and mortality patterns in Europe: Estimates for 40 countries in 2012

INTRODUCTION Cancer incidence and mortality estimates for 25 cancers are presented for the 40 countries in the four United Nations-defined areas of Europe and for the European Union (EU-27) for 2012. METHODS We used statistical models to estimate national incidence and mortality rates in 2012 from recently-published data, predicting incidence and mortality rates for the year 2012 from recent trends, wherever possible. The estimated rates in 2012 were applied to the corresponding population estimates to obtain the estimated numbers of new cancer cases and deaths in Europe in 2012. RESULTS There were an estimated 3.45 million new cases of cancer (excluding non-melanoma skin cancer) and 1.75 million deaths from cancer in Europe in 2012. The most common cancer sites were cancers of the female breast (464,000 cases), followed by colorectal (447,000), prostate (417,000) and lung (410,000). These four cancers represent half of the overall burden of cancer in Europe. The most common causes of death from cancer were cancers of the lung (353,000 deaths), colorectal (215,000), breast (131,000) and stomach (107,000). In the European Union, the estimated numbers of new cases of cancer were approximately 1.4 million in males and 1.2 million in females, and around 707,000 men and 555,000 women died from cancer in the same year. CONCLUSION These up-to-date estimates of the cancer burden in Europe alongside the description of the varying distribution of common cancers at both the regional and country level provide a basis for establishing priorities to cancer control actions in Europe. The important role of cancer registries in disease surveillance and in planning and evaluating national cancer plans is becoming increasingly recognised, but needs to be further advocated. The estimates and software tools for further analysis (EUCAN 2012) are available online as part of the European Cancer Observatory (ECO) (http://eco.iarc.fr).

Recent trends of cancer in Europe: A combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s

INTRODUCTION We present a comprehensive overview of most recent European trends in population-based incidence of, mortality from and relative survival for patients with cancer since the mid 1990s. METHODS Data on incidence, mortality and 5-year relative survival from the mid 1990s to early 2000 for the cancers of the oral cavity and pharynx, oesophagus, stomach, colorectum, pancreas, larynx, lung, skin melanoma, breast, cervix, corpus uteri, ovary, prostate, testis, kidney, bladder, and Hodgkins disease were obtained from cancer registries from 21 European countries. Estimated annual percentages change in incidence and mortality were calculated. Survival trends were analyzed by calculating the relative difference in 5-year relative survival between 1990-1994 and 2000-2002 using data from EUROCARE-3 and -4. RESULTS Trends in incidence were generally favorable in the more prosperous countries from Northern and Western Europe, except for obesity related cancers. Whereas incidence of and mortality from tobacco-related cancers decreased for males in Northern, Western and Southern Europe, they increased for both sexes in Central Europe and for females nearly everywhere in Europe. Survival rates generally improved, mostly due to better access to specialized diagnostics, staging and treatment. Marked effects of organised or opportunistic screening became visible for breast, prostate and melanoma in the wealthier countries. Mortality trends were generally favourable, except for smoking related cancers. CONCLUSION Cancer prevention and management in Europe is moving in the right direction. Survival increased and mortality decreased through the combination of earlier detection, better access to care and improved treatment. Still, cancer prevention efforts have much to attain, especially in the domain of female smoking prevalence and the emerging obesity epidemic.

Geographical patterns and time trends of cancer incidence and survival among children and adolescents in Europe since the 1970s (the ACCIS project): an epidemiological study

BACKGROUND Cancer is rare before age 20 years. We aimed to use the European database of childhood and adolescent cancer cases, within the Automated Childhood Cancer Information System project, to estimate patterns and trends of incidence and survival within Europe. METHODS Comparable, high-quality data from 63 European population-based cancer registries consisted of 113000 tumours in children and 18243 in adolescents diagnosed in 1970-99. Incidence rates and survival were compared by region (east vs west), period, and malignant disease. FINDINGS In the 1990s, age-standardised incidence rates were 140 per million for children (0-14 years) and 157 per million for ages 0-19 years. Over the three decades, overall incidence increased by 1.0% per year (p<0.0001) in children (increases for most tumour types), and by 1.5% (p<0.0001) in adolescents (15-19 years; notable increases were recorded for carcinomas, lymphomas, and germ-cell tumours). Overall 5-year survival for children in the 1990s was 64% in the east and 75% in the west, with differences between regions for virtually all tumour groups; 5-year survival was much the same in adolescents. Survival has improved dramatically since the 1970s in children and adolescents, more so in the west than in the east. INTERPRETATION Our results are clear evidence of an increase of cancer incidence in childhood and adolescence during the past decades, and of an acceleration of this trend. Geographical and temporal patterns suggest areas for further study into causes of these neoplasms, as well as providing an indicator of progress of public-health policy in Europe.

Survival of European children and young adults with cancer diagnosed 1995–2002

This study analyses survival in 40,392 children (age 0-14 years) and 30,187 adolescents/young adults (age 15-24 years) diagnosed with cancer between 1995 and 2002. The cases were from 83 European population-based cancer registries in 23 countries participating in EUROCARE-4. Five-year survival in countries and in regional groupings of countries was compared for all cancers combined and for major cancers. Survival for 15 rare cancers in children was also analysed. Five-year survival for all cancers combined was 81% in children and 87% in adolescents/young adults. Between-country survival differences narrowed for both children and adolescents/young adults. Relative risk of death reduced significantly, by 8% in children and by 13% in adolescents/young adults, from 1995-1999 to 2000-2002. Survival improved significantly over time for acute lymphoid leukaemia and primitive neuroectodermal tumours in children and for non-Hodgkin lymphoma in adolescents/young adults. Cancer survival in patients <25 years is poorly documented in Eastern European countries. Complete cancer registration should be a priority for these countries as an essential part of a policy for effective cancer control in Europe.

Changing epidemiology of malignant cutaneous melanoma in Europe 1953–1997: Rising trends in incidence and mortality but recent stabilizations in Western Europe and decreases in Scandinavia

We analyzed time trends in incidence of and mortality from malignant cutaneous melanoma in European populations since 1953. Data were extracted from the EUROCIM database of incidence data from 165 cancer registries. Mortality data were derived from the WHO database. During the 1990s, incidence rates were by far highest in northern and western Europe, whereas mortality was higher in males in eastern and southern Europe. Melanoma rates have been rising steadily, albeit with substantial geographic variation. In northern Europe, a deceleration in these trends occurred recently in persons aged under 70. Joinpoint analyses indicated that changes in these trends took place in the early 1980s. In western Europe, mortality rates have also recently leveled off [estimated annual percentage change (EAPC) from −13.6% (n.s.) to 3.3%], whereas in eastern and southern Europe both incidence and mortality rates are still increasing [incidence EAPCs 2.3–8.9%, mortality EAPCs −1.8% (n.s.) to 7.2%]. Models including the effects of age, period and birth cohort were required to adequately describe the rising incidence trends in most European populations, with a few exceptions. Time trends in mortality were adequately summarized on fitting either an age‐cohort model (with the leveling off of rates starting in birth cohorts between 1930 and 1940) or an age‐period‐cohort model. The most plausible explanations for the deceleration or decline in the incidence and mortality trends in recent years in northern (and to a lesser extent western) Europe are earlier detection and more frequent excision of pigmented lesions and a growing public awareness of the dangers of excessive sunbathing.

C-Reactive Protein Levels, Variation in the C-Reactive Protein Gene, and Cancer Risk: The Rotterdam Study

PURPOSE It remains unclear if inflammation itself may induce cancer, if inflammation is a result of tumor growth, or a combination of both exists. The aim of this study was to examine whether C-reactive protein (CRP) levels and CRP gene variations were associated with an altered risk of colorectal, lung, breast, or prostate cancer. PATIENTS AND METHODS A total of 7,017 participants age > or = 55 years from the Rotterdam Study were eligible for analyses. Mean follow-up time was 10.2 years. High-sensitivity CRP measurements were performed to identify additional values of 0.2 to 1.0 mg/L compared with standard procedures. Genotypes of the CRP gene were determined with an allelic discrimination assay. RESULTS High levels (> 3 mg/L) of CRP were associated with an increased risk of incident cancer (hazard ratio, 1.4; 95% CI, 1.1 to 1.7) compared with persons with low levels (< 1 mg/L), even after a potential latent period of 5 years was introduced. Although CRP seems to affect several cancer sites, the association was strongest for lung cancer (hazard ratio, 2.8; 95% CI, 1.6 to 4.9). A CRP single nucleotide polymorphism associated with decreased CRP levels was associated with an increased lung cancer risk of 2.6 (95% CI, 1.6 to 4.4) in homozygous carriers. CONCLUSION Baseline CRP levels seem to be a biomarker of chronic inflammation preceding lung cancer, even after subtracting a 5-year latent period. Furthermore, CRP gene variation associated with low CRP blood levels was relatively common in patients with lung cancer. Both chronic inflammation and impaired defense mechanisms resulting in chronic inflammation might explain these results.

The changing epidemiology of lung cancer in Europe.

BACKGROUND Since the incidence and mortality of the histological subtypes of lung cancer in Europe has changed dramatically during the 20th century, we described the variation and changes in incidence, treatment modalities and survival of lung cancer. METHODS For geographical variation and changes in incidence, data of the European cancer incidence and mortality (EUROCIM) database were used, and data on survival were derived from the EUROCARE database. For trends in treatment modalities and survival, according to histology and stage, data of the Eindhoven Cancer registry were used. RESULTS Although the incidence of lung cancer among men in Denmark, Finland, Germany (Saarland), Italy (Varese), the Netherlands, Switzerland and the United Kingdom has been decreasing since the 1980s, the age-adjusted rate for men in other European countries increased at least until the 1990s. Among women the peak in incidence had not been reached in the 1990s. The proportion of adenocarcinoma has been increasing over time; the most likely explanation is the shift to low-tar filter cigarettes. In the 1990s more patients with localised non-small cell lung cancer received surgery than in the 1970s. Among patients with non-localised non-small cell lung cancer and among those with small cell lung cancer there was a trend towards more chemotherapy. There was fairly large variation in survival within Europe. Despite improvement in both the diagnosis and treatment, the overall prognosis for patients with non-small-cell lung cancer hardly improved over time. In contrast, the introduction and improvement of chemotherapy since the 1970s gave rise to an improvement in survival for patients with small-cell lung cancer. CONCLUSION The epidemic of lung cancer is not over yet, especially in southern and eastern Europe. Prevention remains the best policy, but improvement in the management of lung cancer also remains very important.

Understanding variations in survival for colorectal cancer in Europe: a EUROCARE high resolution study

BACKGROUND Marked differences in population based survival across Europe were found for colorectal cancers diagnosed in 1985–1989. AIMS To understand the reasons for these differences in survival in a new analysis of colorectal cancers diagnosed between 1988 and 1991. SUBJECTS A total of 2720 patients with adenocarcinoma of the large bowel from 11 European cancer registries (CRs). METHODS We obtained information on stage at diagnosis, diagnostic determinants, and surgical treatment (not routinely collected by CRs) and analysed the data in relation to three year observed survival, calculating relative risks (RRs) of death and adjusting for age, sex, site, stage, and determinants of stage. RESULTS Three year observed survival rates ranged from 25% (Cracow) to 59% (Modena), and were low in the Thames area (UK) (38%). Survival rates between registries for “resected” patients varied less than those for all patients. When age, sex, and site were considered, RRs ranged from 0.7 (95% confidence intervals (CI) 0.6–0.9) (Modena) to 2.3 (95% CI 1.9–2.9) (Cracow). After further adjustment by stage, between registry RR variation was between 0.8 (95% CI 0.6–0.9) and 1.8 (95% CI 1.5-2.2). Inter-registry RR differences were slightly reduced when the determinants of stage (number of nodes examined and liver imaging) were included in the model. The reduction was marked for the UK registries. CONCLUSIONS The wide differences across Europe in colorectal cancer survival depend to a large extent on differences in stage at diagnosis. There are wide variations in diagnostic and surgical practices. There was a twofold range in the risk of death from colorectal cancer even after adjustment for surgery and disease stage.

Prevalence of co-morbidity in lung cancer patients and its relationship with treatment: A population-based study

BACKGROUND With the rising mean age of lung cancer patients, the number of patients with serious co-morbidity at diagnosis is increasing. As a result, co-morbidity may become an important factor in both the choice of treatment and survival. We studied the prevalence of serious co-morbidity among newly diagnosed lung cancer patients and its association with morphology, stage and treatment. PATIENTS A total of 3864 lung cancer patients registered in the population-based registry of the Comprehensive Cancer Centre South between 1993 and 1995. RESULTS During the study period, the mean age of patients was 67 years (range: 29-93). The most frequent concomitant diseases were cardiovascular diseases (23%), chronic obstructive pulmonary diseases (COPD) (22%) and other malignancies (15%). The prevalence of concomitant diseases was highest for men (60%), patients with squamous-cell carcinoma (64%) and those with a localised tumour (66%). The resection rate for patients < 70 years, with a localised non-small-cell lung tumour, was especially low for those with COPD (67%) or diabetes (64%) compared with patients without concomitant diseases (94%). The association between co-morbidity and chemotherapy for patients with small-cell lung cancer was limited. CONCLUSIONS The prevalence of co-morbidity, especially cardiovascular diseases and COPD, among lung cancer patients is about twice as high as in the general population. Co-morbidity seems to be associated with earlier diagnosis of lung cancer, but it may also lead to less accurate staging and less aggressive treatment. Thus, prognosis is likely to be negatively influenced by co-morbidity.

Less aggressive treatment and worse overall survival in cancer patients with diabetes: A large population based analysis

The purpose of this study was to document the prevalence of diabetes among newly diagnosed cancer patients and to evaluate the influence of diabetes on stage at diagnosis, treatment and overall survival. We performed a population‐based analyses of all 58,498 cancer patients newly diagnosed between 1995 and 2002 in the registration area of the Eindhoven Cancer Registry. Stage of cancer, cancer treatment and comorbidities were actively collected by hospital medical records review. Follow‐up of all patients was completed until January 1, 2005. Nine percent of all cancer patients had diabetes at the time of cancer diagnosis. The prevalence of diabetes was highest among patients with cancer of the pancreas (19%), uterus (14%) and among young men with kidney cancer (8%). Colon, breast and ovarian cancer patients with diabetes were more often diagnosed with a higher tumour stage (p < 0.05). Patients with diabetes and cancer of the oesophagus, colon, breast and ovary were treated less aggressively compared to those without diabetes (p < 0.05). During the follow‐up period 3,902 of 5,555 cancer patients with diabetes died and 29,909 of 52,943 cancer patients without diabetes died. For all cancers combined, in a multivariate cox‐regression model, adjusting for age, gender, stage, treatment and cardiovascular disease, patients with diabetes experienced a significant increase in overall mortality (HR = 1.44, 95% CI 1.40–1.49), ranging however from 0 to 40% for different types of cancer, compared to those without diabetes. In conclusion, diabetic cancer patients frequently were treated less aggressively and had a worse prognosis compared to those without diabetes.