Mariano Santaquilani

EUROCARE-3: survival of cancer patients diagnosed 1990–94—results and commentary

EUROCARE-4 analysed about three million adult cancer cases from 82 cancer registries in 23 European countries, diagnosed in 1995-1999 and followed to December 2003. For each cancer site, the mean European area-weighted observed and relative survival at 1-, 3-, and 5-years by age and sex are presented. Country-specific 1- and 5-year relative survival is also shown, together with 5-year relative survival conditional to surviving 1-year. Within-country variation in survival is analysed for selected cancers. Survival for most solid cancers, whose prognosis depends largely on stage at diagnosis (breast, colorectum, stomach, skin melanoma), was highest in Finland, Sweden, Norway and Iceland, lower in the UK and Denmark, and lowest in the Czech Republic, Poland and Slovenia. France, Switzerland and Italy generally had high survival, slightly below that in the northern countries. There were between-region differences in the survival for haematologic malignancies, possibly due to differences in the availability of effective treatments. Survival of elderly patients was low probably due to advanced stage at diagnosis, comorbidities, difficult access or lack of availability of appropriate care. For all cancers, 5-year survival conditional to surviving 1-year was higher and varied less with region, than the overall relative survival.

Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995–99: results of the EUROCARE-4 study

BACKGROUND EUROCARE is the largest population-based cooperative study on survival of patients with cancer. The EUROCARE project aims to regularly monitor, analyse, and explain survival trends and between-country differences in survival. This report (EUROCARE-4) presents survival data for eight selected cancer sites and for all cancers combined, diagnosed in adult (aged >/=15 years) Europeans in 1995-99 and followed up until the end of 2003. METHODS We analysed data from 83 cancer registries in 23 European countries on 2 699 086 adult cancer cases that were diagnosed in 1995-99 and followed up to December, 2003. We calculated country-specific and mean-weighted age-adjusted 5-year relative survival for eight major cancers. Additionally, case-mix-adjusted 5-year survival for all cancers combined was calculated by countries ranked by total national expenditure on health (TNEH). Changes to survival were analysed relative to cases diagnosed in 1990-94. FINDINGS Mean age-adjusted 5-year relative survival for colorectal (53.8% [95% CI 53.3-54.1]), lung (12.3% [12.1-12.5]), breast (78.9% [78.6-79.2]), prostate (75.7% [75.2-76.2]), and ovarian (36.3% [35.7-37.0]) cancer was highest in Nordic countries (except Denmark) and central Europe, intermediate in southern Europe, lower in the UK and Ireland, and worst in eastern Europe. Survival for melanoma (81.6% [81.0-82.3]), cancer of the testis (94.2% [93.4-95.0]), and Hodgkins disease (80.0% [79.0-81.0]) varied little with geography. All-cancer survival correlated with TNEH for most countries. Denmark and UK had lower all-cancer survival than countries with similar TNEH; Finland had high all-cancer survival, but moderate TNEH. Survival increased and intercountry survival differences narrowed between the data for 1990-94 and 1995-99 for, notably, Hodgkins disease (range 66.1-82.9 [IQR 72.2-78.6] vs 74.0-83.9 [78.6-81.9]), colorectal (29.4-56.7 [45.8-54.1] vs 38.8-59.7 [50.7-57.5]), and breast (61.7-82.7 [72.3-78.3] vs 69.3-87.6 [76.6-82.7]) sites. INTERPRETATION Increases in survival and decreases in geographic differences over time, which are mainly due to improvements in health-care services in countries with poor survival, might indicate better cancer care. Wealthy countries with high TNEH generally had good cancer outcomes, but those with conspicuously worse outcomes than those with similar TNEH might not be allocating health resources efficiently.

Survival trends in European cancer patients diagnosed from 1988 to 1999.

We analysed data from 49 cancer registries in 18 European countries over the period 1988-1999 to delineate time trends in cancer survival. Survival increased in Europe over the study period for all cancer sites that were considered. There were major survival increases in 5 year age-adjusted relative survival for prostate (from 58% to 79%), colon and rectum (from 48% to 54% men and women), and breast (from 74% to 83%). Improvements were also significant for stomach (from 22% to 24%), male larynx (from 62% to 64%), skin melanoma (from 78% to 83%), Hodgkin disease (from 77% to 83%), non-Hodgkin lymphoma (from 49% to 56%), leukaemias (from 37% to 42%), and for all cancers combined (from 34% to 39% in men, and from 52% to 59% in women). Survival did not change significantly for female larynx, lung, cervix or ovary. The largest increases in survival typically occurred in countries with the lowest survival, and contributed to the overall reduction of survival disparities across Europe over the study period. Differences in the extent of PSA testing and mammographic screening, and increasing use of colonoscopy and faecal blood testing together with improving cancer care are probably the major underlying reasons for the improvements in survival for cancers of prostate, breast, colon and rectum. The marked survival improvements in countries with poor survival may indicate that these countries have made efforts to adopt the new diagnostic procedures and the standardised therapeutic protocols in use in more affluent countries.

The cure of cancer: A European perspective

Cancer survival analyses based on cancer registry data do not provide direct information on the main aim of cancer treatment, the cure of the patient. In fact, classic survival indicators do not distinguish between patients who are cured, and patients who will die of their disease and in whom prolongation of survival is the main objective of treatment. In this study, we applied parametric cure models to the cancer incidence and follow-up data provided by 49 EUROCARE-4 (European Cancer Registry-based study, fourth edition) cancer registries, with the aims of providing additional insights into the survival of European cancer patients diagnosed from 1988 to 1999, and of investigating between-population differences. Between-country estimates the proportion of cured patients varied from about 4-13% for lung cancer, from 9% to 30% for stomach cancer, from 25% to 49% for colon and rectum cancer, and from 55% to 73% for breast cancer. For all cancers combined, estimates varied between 21% and 47% in men, and 38% and 59% in women and were influenced by the distribution of cases by cancer site. Countries with high proportions of cured and long fatal case survival times for all cancers combined were characterised by generally favourable case mix. For the European pool of cases both the proportion of cured and the survival time of fatal cases were associated with age, and increased from the early to the latest diagnosis period. The increases over time in the proportions of Europeans estimated cured of lung, stomach and colon and rectum cancers are noteworthy and suggest genuine progress in cancer control. The proportion of cured of all cancers combined is a useful general indicator of cancer control as it reflects progress in diagnosis and treatment, as well as success in the prevention of rapidly fatal cancers.

The EUROCARE-5 study on cancer survival in Europe 1999–2007: Database, quality checks and statistical analysis methods

BACKGROUND Since 25years the EUROCARE study monitors the survival of cancer patients in Europe through centralised collection, quality check and statistical analysis of population-based cancer registries (CRs) data. The European population covered by the study increased remarkably in the latest round. The study design and statistical methods were also changed to improve timeliness and comparability of survival estimates. To interpret the EUROCARE-5 results on adult cancer patients better here we assess the impact of these changes on data quality and on survival comparisons. METHODS In EUROCARE-5 the survival differences by area were studied applying the complete cohort approach to data on nearly nine million cancer patients diagnosed in 2000-2007 and followed up to 2008. Survival time trends were analysed applying the period approach to data on about 10 million cancer cases diagnosed from 1995 to 2007 and followed up to 2008. Differently from EUROCARE-4, multiple primary cancers were included and relative survival was estimated with the Ederer II method. RESULTS EUROCARE-5 covered a population of 232 million resident persons, corresponding to 50% of the 29 participating countries. The population coverage increased particularly in Eastern Europe. Cases identified from death certificate only (DCO) were on average 2.9%, range 0-12%. Microscopically confirmed cases amounted to over 85% in most CRs. Compared to previous methods, including multiple cancers and using the Ederer II estimator reduced survival estimates by 0.4 and 0.3 absolute percentage points, on average. CONCLUSIONS The increased population size and registration coverage of the EUROCARE-5 study ensures more robust and comparable estimates across European countries. This enlargement did not impact on data quality, which was generally satisfactory. Estimates may be slightly inflated in countries with high or null DCO proportions, especially for poor prognosis cancers. The updated methods improved the comparability of survival estimates between recently and long-term established registries and reduced biases due to informative censoring.

Age and case mix-standardised survival for all cancer patients in Europe 1999–2007: Results of EUROCARE-5, a population-based study

BACKGROUND Overall survival after cancer is frequently used when assessing a health care services performance as a whole. It is mainly used by the public, politicians and the media, and is often dismissed by clinicians because of the heterogeneous mix of different cancers, risk factors and treatment modalities. Here we give survival details for all cancers combined in Europe, correlating it with economic variables to suggest reasons for differences. METHODS We computed age and cancer site case-mix standardised relative survival for all cancers combined (ACRS) for 29 countries participating in the EUROCARE-5 project with data on more than 7.5million cancer cases from 87 population-based cancer registries, using complete and period approach. RESULTS Denmark, United Kingdom (UK) and Eastern European countries had lower survival than neighbouring countries. Five-year ACRS has been increasing throughout Europe, and substantial increases, between 1999-2001 and 2005-2007, have been achieved in countries where survival was lower in the past. Five-year ACRS for men and women are positively correlated with macro-economic variables like the Gross Domestic Product (GDP) and Total National Expenditure on Health (TNEH) (R2 about 70%). Countries with recent larger increases in GDP and TNEH had greater increases in cancer survival. CONCLUSIONS ACRS serves to compare all cancer survival in Europe taking account of the geographical variability in case-mixes. The EUROCARE-5 data on ACRS confirm previous EUROCARE findings. Survival appears to correlate with macro-economic determinants, particularly with investments in the health care system.

Life tables for world-wide comparison of relative survival for cancer (CONCORD study)

Background The CONCORD study compares population-based relative survival from cancer using data from cancer registries in five continents. To estimate relative survival, general mortality life tables are required. Available statistics are incomplete, so various approaches are used to construct complete life tables. This article outlines how the life tables were constructed for CONCORD; it compares life expectancy at birth between 101 populations covered by cancer registries in 31 countries and compares the impact of two approaches to the deployment of life tables in relative survival analysis. Methods The CONCORD approach, using specific mathematical methods, produced complete (single-year-of-age) life tables by sex, cancer registry area, calendar year (1990–1999) and race (only in the USA). In order to study the impact of different approaches, we compared relative survival in the USA using the US national life table, centered on the relevant census years, and the CONCORD approach. We estimated relative survival in each American participating cancer registry for patients diagnosed with breast (women), colorectal or prostate cancer during 1990–1994 and followed up to 1999. Results Average life expectancy at birth during 1990–1999 varied in CONCORD cancer registry areas from 64 to 78 years in males and from 71 to 84 years in females. It increased during the 1990s more in men than in women. In the USA, it was lower in blacks than in whites. Relative survival in American populations was lower with the CONCORD approach, which incorporates trends and geographic variation in background mortality, than with the USA census life tables. Conclusions International variation in background mortality by geographic area, calendar time, race, age and sex is wide. We suggest that in international comparisons of cancer relative survival, complete life tables that are specific for cancer registry area, calendar year and race should be used.

A retrospective cohort mortality study of Italian commercial airline cockpit crew and cabin attendants, 1965-96.

Abstract A retrospective cohort mortality study was conducted among Italian commercial flight personnel for the period 1965-1996. The cohort was composed of 3,022 male cockpit crew members and 3,418 male and 3,428 female cabin attendants. Cause-specific standardized mortality ratios (SMRs) and exact 95% confidence intervals. (CIs) were calculated as estimates of the relative risk. Mortality from all cancers was less than expected forall categories (SMRs of 0.58 for male cockpit crew, 0.67 for male cabin attendants, and 0.90 for female cabin attendants). Among male flight persopnel, the SMR for leukemia was somewhat elevated (SMR 1.73; 95% CI: 0.75–3.41) based on eight deaths, with a positive trend by length of employment (p = 0.046). Additionally, an excess of death by suicide was seen among female cabin attendants (SMR 3.38; 95% CI: 1.24–7.35). Other Italian studies of flight personnel are under way, including a detailed assessment of cosmic radiation exposure and investigations of non-radiation occupational risk factors and prevalence of nonfatal outcomes.

Health Risks from Radiation Exposure for Civilian Aviation Flight Personnel: A Study of Italian Airline Crew Members

Abstract De Angelis, G., Caldora, M., Santaquilani, M., Scipione, R. and Verdecchia, A. Health Risks from Radiation Exposure for Civilian Aviation Flight Personnel: A Study of Italian Airline Crew Members. Radiat. Res. 156, 689–694 (2001). A study of the effects of exposures of civilian aviation flight personnel to atmospheric ionizing radiation (including high-energy neutrons) is being performed. The results of previous studies and of the criteria required for a more satisfactory outcome in future studies are presented, along with a description of the protocol for the Italian national study. A description of the cohort is given in terms of its size, composition and member eligibility. The various ways of determining the exposure and the health status of past and current aircrew members are discussed, and follow-up procedures are described. An overview of the data management and processing philosophy adopted in the Italian study is given with regard to flight routes, radiation dose evaluation along the flight paths, and construction of exposure matrices. Other studies of potential interest are also discussed. The study is still in progress, so the results are preliminary.

Radiation-induced health effects on atmospheric flight crew members: clues for a radiation-related risk analysis

There are few human data on low-dose-rate-radiation exposure and the consequent acute and late effects. This fact makes it difficult to assess health risks due to radiation in the space environment, especially for long-term missions. Epidemiological data on civilian flight personnel cohorts can provide information on effects due to the low-dose and low-dose rate mixed high- and low-LET radiation environment in the earths atmosphere. The physical characteristics of the radiation environment of the atmosphere make the results of the studies of commercial flight personnel relevant to the studies of activities in space. The cooperative international effort now in progress to investigate dose reconstructions will contribute to our understanding of radiation risks for space exploration.