Content area
[...] even though cancer registration is constantly improving in the UK, one cannot dismiss that gaps in case ascertainment in England might be responsible for a proportion of the survival differences when comparisons are made with those countries having nearly complete case ascertainment, for example Sweden. [...] early detection could simply increase the time between diagnosis and death, without modifying the fatal outcome but increasing survival (lead-time bias).
In The Lancet, Michel Coleman and co-workers present changes in survival of patients with breast, colorectal, ovarian, and lung cancer in six countries (UK, Sweden, Norway, Australia, Canada, Denmark). The researchers used adequate data to examine trends in incidence, mortality, and survival from 1990 to 2007.1 The merit of this paper is its ability to display relative survival together with incidence and mortality trends.
The paper opens by stating: "Survival is a key index of the overall effectiveness of health services in the management of patients with cancer." Effectiveness can be understood as the contributions of early cancer detection and of the quality of patients' management. However, the interpretation of survival data is a major challenge. The panel summarises factors that can influence the survival of patients with cancer. When countries are compared, because of the complexity and intricacy of factors influencing survival statistics (including the fact that health systems differ in many ways), many factors not associated with performance can influence variations in survival.
Administrative limitations in cancer registration have been suggested to explain the lower survival rates of patients with cancer in the UK; such limitations include registration of date of recurrence instead of date of diagnosis and absence of registration of some long-term survivors.2 Such critiques have been challenged for the Scottish data,3 which were not included in the UK data used by Coleman and co-workers. Furthermore, in Denmark, where cancer registration is compulsory and of high quality, survival statistics are similar to those observed in the UK. However, the large Thames Cancer Registry in England reported that the estimated completeness of case ascertainment in 1990-2001 was 85.0% for breast cancer and 87.8% for colorectal cancer.4 In Finland, a country with longstanding compulsory cancer registration, these figures were 98.5% and 98.8%, respectively. Lack of ascertainment mainly concerns long-term survivors. Hence, even though cancer registration is constantly improving in the UK, one cannot dismiss that gaps in case ascertainment in England might be responsible for a proportion of the survival differences when comparisons are made with those countries having nearly complete case ascertainment, for example Sweden.
Survival differences could be due to differences in exposure to cancer risk factors. For instance, obesity is associated with breast cancers of worse prognosis that are less sensitive to treatment.5 The prevalence of obesity in adult women around 2000 was 20% in the UK and 9% in Sweden,6 a difference that might play a role in the dissimilarity in breast cancer survival.
Adjustment of cancer survival statistics for stage at diagnosis usually leads to a substantial decrease in survival differences between areas,7-9 indicating that variations in cancer stage are a factor of considerable variation in survival. Detection of a cancer at an earlier stage or when the primary tumour is still small could allow for more efficient treatment, often leading to mortality reduction and improved survival. Early detection might improve survival in the absence of any effect on mortality for two reasons. First, early detection could simply increase the time between diagnosis and death, without modifying the fatal outcome but increasing survival (lead-time bias). Second, earlier detection methods, such as mammography, often find slow-progressing organ-confined cancers, most of which would not have become clinically apparent and life-threatening (overdiagnosis). 10,11 Increased detection of indolent cancers will increase incidence without changing mortality, driving survival statistics towards higher values (length-time bias).12,13 For instance, in 2000-07, the 5-year relative survival of Norwegian patients with breast cancer was greater than the rates of the UK and lower than that in Sweden in Coleman and colleagues' paper; however, in 2000, breast cancer mortality in Norway was close to that in Sweden and after 2003, it was lower. Invitation to mammography screening started about 12 years later in Norway than in Sweden,14,15 possibly indicating that the higher survival in Sweden could be due to earlier and more intense screening, resulting in greater screen-detection of small non-life-threatening cancers. To establish how early cancer incidence contributed to differences in survival, stage-specific incidence rates need to be compared.
The comparison between Norway and Sweden indicates that survival is not always consistent with incidence and mortality. A further example is the 5-year survival of patients with colorectal cancer, which was 15% lower in the UK than in Sweden in 1995-99. This difference decreased slightly to 11% in 2005-07 but it remained the worst among the six countries. In 1985, colorectal cancer mortality was 36% higher in the UK than in Sweden. After a constant drop, this figure reduced to 1% in 2007 and was lower than mortality observed in the four other countries. Incidence curves remained broadly parallel. The quasi-constancy of the differences in 5-year survival data does not at all reflect the kinetic of mortality trends. Even more than for breast cancer, colorectal cancer survival statistics depict a demoralising stagnating lack of effectiveness in the UK health system, while mortality data provide strong evidence that efforts deployed over the past two decades are paying off. Discussion of reasons underlying the contrast between mortality and survival is beyond the scope of this commentary and would require additional data. However, colorectal cancer data show that, contrary to what is claimed by Coleman and co-workers, mortality is not a function of both incidence and survival.
To compare possible determinants of survival between countries, high-resolution studies retrospectively collect clinical information on stage at diagnosis and on treatment. 16 To what extent these studies in their current design will help to explain differences in survival is still unclear. For instance, the largest European population-based study collecting information on stage, diagnostic procedures, and treatment for patients with breast cancer diagnosed mainly in 1996-98 showed that Swedish patients received less radiotherapy and less chemotherapy than did patients from other countries;17 in particular, older Swedish patients were largely undertreated. These findings are surprising, in view of the high survival of Swedish patients with breast cancer. By contrast, Allemani and colleagues reported data that correlates well with the observation that, from 1989 to 2006, breast cancer mortality in Sweden only moderately declined, especially in older patients.18
When factors likely to influence survival statistics are similar across medical facilities, or when data on these factors are available, survival statistics might bring insights into the respective roles of detection and treatment.19 When comparing countries, however, as certain studies have started to do,20,21 country-specific cancer survival data should always be considered together with both incidence and mortality data, and one should always consider the multiple factors unrelated to health-system performance that could influence survival data.
1 Coleman MP, Forman D, Bryant H, and the ICBP Module 1 Working Group. Cancer survival in Australia, Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the International Cancer Benchmarking Partnership): an analysis of population-based cancer registry data. Lancet 2011; 377: 127-38.
2 Beral V, Peto R. UK cancer survival statistics. BMJ 2010; 341: c4112.
3 Brewster DH, Black RJ. Survival is multifactorial. BMJ 2010; 341: c5133.
4 Robinson D, Sankila R, Hakulinen T, Møller H. Interpreting international comparisons of cancer survival: the effects of incomplete registration and the presence of death certificate only cases on survival estimates. Eur J Cancer 2007; 43: 909-13.
5 Ewertz M, Jensen MB, Gunnarsdóttir KA, et al. Effect of obesity on prognosis after early-stage breast cancer. J Clin Oncol 2010; published online Nov 29. DOI:10.1200/JCO.2010.29.7614.
6 Boniol M, Autier P. Prevalence of main cancer lifestyle risk factors in Europe in 2000. Eur J Cancer 2010; 46: 2534-44.
7 Sant M, Allemani C, Capocaccia R, et al. Stage at diagnosis is a key explanation of differences in breast cancer survival across Europe. Int J Cancer 2003; 106: 416-22.
8 Sant M, Allemani C, Berrino F, et al. Breast cancer survival in Europe and the United States. Cancer 2004; 100: 715-22.
9 Ciccolallo L, Capocaccia R, Coleman MP, et al. Survival differences between European and US patients with colorectal cancer: role of stage at diagnosis and surgery. Gut 2005; 54: 268-73.
10 Zahl PH, Mæ hlen J, Welch HG. The natural history of invasive breast cancers detected by screening mammography. Arch Intern Med 2008; 168: 2311-16.
11 Morrell S, Barratt A, Irwig L, Howard K, Biesheuvel C, Armstrong B. Estimates of overdiagnosis of invasive breast cancer associated with screening mammography. Cancer Causes Control 2010; 21: 275-82.
12 Welch HG, Schwartz LM, Woloshin S. Are increasing 5-year survival rates evidence of success against cancer? JAMA 2000; 283: 2975-78.
13 Autier P, Boniol M, Héry C, Masuyer E, Ferlay J. Cancer survival statistics should be viewed with caution. Lancet Oncol 2007; 8: 1050-52.
14 Kalager M, Zelen M, Langmark F, Adami HO. Effect of screening mammography on breast-cancer mortality in Norway. N Engl J Med 2010; 363: 1203-10.
15 Olsson S, Andersson I, Karlberg I, Bjurstam N, Frodis E, Håkansson S. Implementation of service screening with mammography in Sweden: from pilot study to nationwide programme. J Med Screen 2000; 7: 14-18.
16 Berrino F, De Angelis R, Sant M, et al. Survival for eight major cancers and all cancers combined for European adults diagnosed in 1995-99: results of the EUROCARE-4 study. Lancet Oncol 2007; 8: 773-83.
17 Allemani C, Storm H, Voogd AC, et al. Variation in 'standard care' for breast cancer across Europe: a EUROCARE-3 high resolution study. Eur J Cancer 2010; 46: 1528-36.
18 Autier P, Boniol M, LaVecchia C, et al. Disparities in breast cancer mortality trends between thirty European countries: a descriptive epidemiology analysis. BMJ 2010; 341: c3620.
19 Thomson CS, Brewster DH, Dewar JA, Twelves CJ. Improvements in survival for women with breast cancer in Scotland between 1987 and 1993: impact of earlier diagnosis and changes in treatment. Eur J Cancer 2004; 40: 743-53.
20 de Vries E, Karim-Kos HE, Janssen-Hijnen MLG, Soerjmataram I, Kiemeney LA, Coebergh JWW. Explanations for worsening cancer survival. Nat Rev Clin Oncol 2010; 7: 60-63.
21 Karim-Kos HE, de Vries E, Soerjomataram I, Lemmens V, Siesling S, Coebergh JWW. Recent trends of cancer in Europe: a combined approach of incidence, survival and mortality for 17 cancer sites since the 1990s. Eur J Cancer 2008; 44: 1345-89.
*Philippe Autier, Mathieu Boniol
International Prevention Research Institute (iPRI), 69006 Lyon, France
We declare that we have no conflicts of interest.
Copyright Elsevier Limited Jan 8-Jan 14, 2011