This study provides population-based survival estimates for 2·4 million adults diagnosed with a cancer of the colorectum, lung, breast, or ovary up to 2007, in six countries (panel
). Of the combined population of 123 million, 81% were covered by participating cancer registries. Data quality control and analyses were both done centrally with a common protocol, overseen by external experts. Data quality was high; less than 5% of eligible records (102 997/2 504 741) had to be excluded. Participating registries judged the survival estimates to be compatible with their own results, despite methodological differences.
Panel. Research in context
studies have shown wide international differences in population-based cancer survival in patients diagnosed from the 1980s to 2002. The differences represent many avoidable premature deaths, and they have helped to drive national cancer control strategies since 2000. This international study is the first phase in a programme to identify the reasons for persistent inequalities in survival, as the evidence base for health policy to reduce them.
We compared survival from cancers of the colorectum, lung, breast, and ovary in six countries for patients diagnosed between 1995 and 2007. The countries selected for study have similar wealth, universal health coverage, and high-quality cancer registration. Survival has continued to improve for each cancer in all six countries, but generally remains higher in Australia, Canada, and Sweden, intermediate in Norway, and lower in Denmark and the UK. The patterns are consistent with later stage at diagnosis or differences in treatment, particularly in Denmark and the UK and in older patients, and they prompt further examination of stage and treatment by the International Cancer Benchmarking Partnership to explain the differences in survival.
Survival improved for all four cancers in all six countries during 1995–2007, although there was some fluctuation within countries. Generally, Australia, Canada, and Sweden had the highest survival, with Norway somewhat lower. Survival was generally lowest in Denmark and the three UK nations. The largest gains were recorded for colorectal cancer, and the smallest for lung and ovarian cancer. Relative survival from breast cancer at 1 year exceeded 90% in all six countries; gains were smaller, and the international range in both 1-year and 5-year survival diminished. For cancers of the colorectum, lung, and ovary, survival at 1 year was generally lower in Denmark and the three UK nations, suggesting that late diagnosis is still a problem in both countries; however, 1-year survival has increased more in Denmark since 2000–02 than in the UK.
The incidence of invasive ovarian malignancy has been falling in all six countries since 1985 (webappendix p 28
). The decrease since 2000 might be partly attributable to reclassification of some tumours of borderline malignancy from invasive, malignant behaviour (code 3) in ICD-O-2 to uncertain behaviour (code 1) in ICD-O-3, but the protective effect of oral contraception and increased diagnostic intensity, with earlier diagnosis and removal of borderline or premalignant lesions, could have contributed in the long term.25
However, survival analyses were restricted to invasive cancers, so this shift would tend to reduce overall survival in the tumours still classified as invasive, by removing up to 10% of tumours with good survival. Since survival actually rose in most jurisdictions, any effect of this change seems to have been small.
We included both first and second (or higher-order) primary cancers in the analyses. The highest proportion of second and higher-order cancers was recorded in Manitoba, one of the oldest registries, and for three of the four cancers, the lowest proportion was in Northern Ireland, the newest registry (webappendix p 19
). Sensitivity analyses will be done to show the effect on survival estimates of including these patients. The effect on 5-year survival is unlikely to exceed 1%.12
International differences in survival cannot simply be attributed to poor-quality cancer registration, as has been suggested for breast cancer in the UK in particular.26
Incidence, survival, and mortality trends are coherent for breast and other cancers (webappendix p 28
), as they were when this issue was last discussed 10 years ago.27,28
For example, although breast cancer mortality in the UK has decreased more quickly than in Sweden since 1985, it is still higher, whereas incidence has risen roughly in parallel, and the difference in survival has decreased (compare and ). The Danish cancer registry is also highly regarded, with high-quality data, yet cancer survival patterns and trends in Denmark have been similar to those in the UK for several years, and the survival deficit with respect to other Nordic countries has motivated cancer strategy in Denmark, as in Britain.
3-year moving-average world-standardised incidence and mortality rates per 100 000 population per year, 1985–2005, by country, for breast cancer in women and colorectal cancer in men and women combined
Mortality-incidence ratios for breast cancer in 2000 are also somewhat higher in Denmark and the UK than in other countries (webappendix p 27
). A large study has shown that breast cancer incidence recorded independently in primary care in the UK during 1990–96 was very similar to incidence in the national cancer registry.29
Several studies have shown that access to radiotherapy varies widely in the UK; that manpower was low in the 1990s; and that elderly people and less affluent groups were affected by late diagnosis, treatment delays, and a survival deficit.30,31
Late-stage diagnosis accounts for much of the European variation in survival. High-resolution studies of hospital medical records (rather than cancer registry data) have shown that women with breast cancer in the UK were operated less often, have axillary dissection less often, and have fewer nodes sampled than do women in other countries.32
A study of more than 13 000 medical records has shown striking variation in breast cancer treatment in Europe in the late 1990s.33
Errors do arise in cancer registration, but the UK survival deficit is not explained by routine registration of recurrences as new diagnoses, or by failing to register long-term survivors. We will investigate this topic in a separate report.
Other studies have suggested that the wide differences in survival within Europe could be explained by large variation in diagnostic and surgical practice for colorectal cancer34
and in stage at diagnosis and treatment for breast cancer.32,35
Women older than 65 years with breast cancer in the late 1990s in England were less likely than younger women to receive triple assessment or guideline radiotherapy after conservative surgery.36
Chemotherapy and radiotherapy were later shown to increase long-term survival in early breast cancer. In Europe more generally, relative survival has improved more for women younger than 65 years at diagnosis than for older women; the widening deficit in survival in older women arises mainly in the first year after diagnosis, suggesting later diagnosis or less access to treatment.37
Survival from colorectal and breast cancers in England and Denmark is lower than in Australia, Canada, and most Nordic and western European countries.1,2,5,11
Improvements in colorectal cancer survival in England seem coherent with incidence and mortality trends.38
The lung cancer survival deficit in Denmark has been attributed to later stage at diagnosis and to the distribution of morphological types.39
The findings in this paper comprise a public health comparison of the survival of all patients with cancer in each jurisdiction, irrespective of stage at diagnosis or treatment, but after international differences in non-cancer mortality by age, sex, and calendar period are taken into account. Differences in individual, health-system, and clinical factors—such as public awareness of cancer, diagnostic delay, stage, comorbidity, and access to optimal treatment—are all potential explanations for the overall differences in relative survival. We will examine later the extent to which differences in stage at diagnosis, morphological type, and treatment for each patient can explain the survival disparities reported in this study, to provide evidence for strategy on how best to reduce the differences. Obesity, physical activity, and other lifestyle variables might also affect outcome.
Indicators of trend in incidence, survival, and mortality are all required for cancer control. Incidence rates refer to patients with cancer who are diagnosed in a specific year. Almost all are registered, but those who are not might be a biased subset. Most cancers are registered from more than one data source, with pathological evidence of the diagnosis, but a small proportion are registered only from a death certificate. Data quality control is extensive and well documented.13
Survival also refers to patients diagnosed in a specific year. Relative survival is not subject to errors in certification of the cause of death, and is corrected for background mortality, but it is subject to lead-time bias. It reflects the overall outcome for all patients with cancer, not only those in clinical trials or those diagnosed early enough for treatment of curative intent. Relative survival is a measure of the overall effectiveness of the entire health system, not only of treatment.
Mortality is a function of both incidence and survival. Mortality rates refer to the number of people who die in a specific year. Lung cancer survival has been low for many years, so mortality trends are largely parallel with incidence trends (webappendix p 28
). By contrast, more than 40% of women who die of breast cancer in a specific year will have been diagnosed at least 5 years previously, so trends in mortality provide a delayed and imprecise picture of any trends in survival. It is not possible to draw conclusions about trends in survival from trends in mortality alone. Unlike relative survival, mortality rates are subject to errors in certification of the cause of death, particularly in elderly patients. Autopsies are infrequent, and quality control of death certificate data is far more limited than that of incidence data. Mortality data are nevertheless almost complete, and long time series are available. They are an invaluable public health resource.
The consistency of incidence, survival, and mortality trends in Europe has led other investigators to conclude that joint interpretation of these indicators is the best guide to policy for prevention, screening, treatment, and the organisation of health-care systems.40
We agree with this conclusion. Primary prevention to reduce incidence remains the best long-term strategy to reduce the cancer burden; incidence trends will thus remain a crucial policy guide. Until the causes of cancer are more fully understood, however, and effective strategies for prevention are fully implemented, millions of people will continue to be diagnosed with cancer every year. Therefore, for policy makers who have to deliver effective care to these patients, population-based survival will also remain a key indicator of progress. Even small improvements in survival from common cancers can prevent large numbers of premature deaths.41
Cancer registration systems should be supported to improve the quality and completeness of their data. Systematic collection of data for comorbidity and other possible determinants of survival should also be introduced. Clinicians should be encouraged to record the data that are needed for population-based comparisons more systematically. Information systems should be improved to help with recording of these data.
Additional indicators for routine monitoring of progress in cancer control are needed. For example, differences in relative survival between two countries or regions can be expressed as the number of cancer-related (excess) deaths in patients with cancer in one country that would be avoidable within, say, 5 years of diagnosis if relative survival were as high as in the other country.6
A decrease in the number of such avoidable, premature deaths can provide a useful comparative index of progress; it incorporates the relative effectiveness of both health systems, remains applicable when survival is improving in both countries, and might be more readily understood by the general public.
Survival trends can help both in the formulation of strategies for cancer control and in the assessment of their effectiveness. The International Cancer Benchmarking Partnership aims to provide robust and timely comparison of trends in cancer survival between countries or regions with good population-based data. Later phases of this partnership will explore the effect on international survival disparities of differences in public awareness and beliefs about cancer, duration of symptoms, diagnosis in primary and secondary care, comorbidity, and access to treatment. The goal is to identify remediable causes of survival deficits, to inform the development of new cancer control policy in participating countries.