Result card

  • CUR9: What is the burden of CRC?
English

What is the burden of CRC?

Authors: Mirjana Huic, Eleftheria Karampli, Silvia Florescu, Cipriana Mihaescu-Pintia

Internal reviewers: Laura Cacciani, Sophie Brunner, Esther Kraft

Incidence, prevalence, survival

Colorectal cancer (CRC) is the 3rd most common cancer worldwide, and the second most frequent in developed countries {5}. In 2008, there were 1,234,000 estimated cases of CRC worldwide, the majority of which (60%) occurred in the most developed countries {6}. The disease is more common in westernized countries than Asia or Africa. The estimated age-standardized incidence rate [world age standardization (ASR-W)] of CRC in 2008 was 17.2 per 100,000 inhabitants; however, there are large variations between regions. Incidence rates are higher in Australia/New Zealand (39.0 per 100,000), Western Europe (33.1 per 100,000) and Southern Europe (31.1 per 100,000) and lower in Western Africa (4.9 per 100,000), South-Central Asia (4.5 per 100,000) and Middle Africa (3.7 per 100,000) {6}. The number of deaths due to CRC worldwide in 2008 was estimated at 608,000, equivalent to 8% of total cancer-related deaths. CRC was the third cause of cancer-related death in women (after breast and lung cancer) and the fourth (after lung, liver and stomach cancer) in men {6}. Estimated CRC age-standardized mortality rates (world age standardization) in both sexes were highest in Central and Eastern Europe (15.1 per 100,000) and lowest in Middle Africa (3.1 per 100,000) {6}. As the case in incidence, mortality from CRC is higher in men that in women.

Focusing on Europe, in 2008, CRC accounted for 12.4% of deaths caused by malignancy in European countries (11.5% and 13.5% of total cancer deaths in men and women respectively)  {6}.  It represented the second cause of cancer death for the total population, lung cancer being the first. The number of deaths attributed to CRC in Europe in 2008 was 212,219. According to estimates on cancer incidence in Europe {6}, in 2008 CRC was the most frequent malignancy in both sexes, comprising 13.5% of all newly-diagnosed carcinomas in the European population (men 13.5%, women 13.5%). Breast cancer and lung cancer were the 2nd and 3rd most frequent malignancies respectively (13.2% and 12.1% of all malignancies in both sexes). Overall, 432,414 people were estimated to have been newly diagnosed in 2008 with CRC in Europe. A more detailed analysis of individual diagnoses from 96 individual cancer registries in Europe for the period 1998-2002 identified malignant disease of the colon as the most frequent, accounting for 57% of all cases (> 35 cases/100,000 inhabitants), followed by malignant diseases of the rectum and rectosigmoid {5}.

Variations are observed in CRC incidence and mortality rates among European countries {6}. Age-standardized incidence rates estimates (European age standard) range from 106 per 100,000 in Hungary to 13.6 per 100,000 in Albania for men and from 55.6 per 100,000 in Switzerland to 21.3 per 100,000 in Greece for women. Estimated age-standardized mortality rates (ASR-W) were higher in Hungary, the Czech Republic and Slovakia and lowest in Iceland, Albania and Cyprus. The mortality rate for Europe was 13.3 per 100,000 population {6}. Part of the differences in CRC incidence and mortality can be explained by differences in lifestyle, screening practices and treatment patterns between countries {2}. However, a detailed comparison of data for European countries is made difficult because of the absence of unified data, as not all countries maintain population and cancer registers {5}. European funded projects such as EUROCARE have aimed at collecting standardised information.

In addition to CRC incidence and mortality, population-based survival is an important indicator for evaluating management of CRC {7}. Survival rates are strongly associated with stage of CRC at diagnosis (see related Table in CUR2). Data on cancer survival for European countries are available through various national and/or regional cancer registries and through the EUROCARE (European cancer registry-based study of cancer patients’ survival and care) study. 5-year relative CRC survival rates in 2004-2009 for European countries for which data were available varied from 38.6% in Latvia to 66.1% in Iceland as is depicted in Table 1. There are significant differences in relative survival rates between European countries. CRC survival disparities have also been observed within countries between geographical regions and ethnic or racial groups {7-9}.

Table 1: Colorectal cancer five-year relative survival rate, 2004-2009 (or nearest period)

Age-sex standardised rate per 100 patients

 

2004-2009

 

Value

 

95% CI deviation

Belgium

64.7

 

1.8

Austria

63.1

 

1.9

Finland

61.8

2003-08

1.1

Netherlands

61.0

 

1.2

Sweden

60.7

 

1.0

Germany

60.4

2003-08

0.8

Portugal

57.4

 

0.0

Slovenia

55.8

 

3.2

Denmark

55.5

 

2.1

United Kingdom

53.3

 

0.6

Ireland

52.9

 

1.6

Czech Republic

49.6

2003-08

0.7

Latvia

38.6

 

4.2

Norway

63.1

 

1.7

Iceland

66.1

2003-08

9.5

Source: OECD Health Data 2012

 

An important source of information regarding CRC survival rates in Europe are the findings of the EUROCARE study, which began in 1989 and is the most extensive population study monitoring relative survival rate (RSR) {5}. Its aim is to measure and explain international differences in cancer survival in Europe, by using standard definitions, quality control and standard analytic techniques and taking into consideration the demographic variables and background mortality in the participating countries {10}. The indicator that is predominantly used is the 5-year relative CRC survival rate, defined as "the ratio of the recorded survival to the expected survival in the general population of the same age and sex" {7}. The most recent publications include data up to the EUROCARE-4 round, which collected information from 83 cancer registries in 23 European countries on adults diagnosed with cancer in 1995–99 and followed up to December 2003. According to the study results {7}, mean European age-adjusted 5-year relative survival of both sexes for colorectal cancer was 53.8% [95% CI 53.3-54.1]. CRC 5-year survival was >57% in the Nordic countries (except Denmark) and some countries of central and southern Europe, but 51% in the UK. Relative survival rates in eastern European countries were lower (<45%). Survival, however, presents a continuous increase over the period of 1991–2002 in all countries, with the largest improvements observed in eastern European countries, thus, decreasing the gap between the various European areas {11}.

 

Trends in incidence, mortality and survival

In Europe, an increasing trend in average incidence of CRC has been observed in recent years (2001-2005) {5}. However, these trends have not been uniform. Analysis of cancer registries' data in 21 European countries from the mid-1990s to approximately 2005 {12} showed a modest increase on average in CRC incidence among males, whereas in women CRC incidence rates remained stable and even decreased in some countries. Internationally, CRC incidence rates have been stabilizing or declining in historically high-risk areas (United States, New Zealand, Canada), but rapidly increasing in several historically low-risk countries, including Japan, Korea, China, and Eastern European countries {13}.

Observed increases in cancer incidence might relate to increasing risk factors or improvements in the diagnosis and recording of cancer cases and early detection through population screening {12}. For example, the increase in incidence rates in several Asian and Eastern European countries as well as in Spain has been attributed largely to changes in risk factors (changes in dietary and physical activity patterns, smoking) that are most likely related to their westernization {12, 13}. In Japan both increased screening and the transition to a more westernized lifestyle with changes in dietary intake have been reported as the main explanatory factors for the increases in CRC incidence {14}. On the contrary, in the US the decrease in CRC incidence observed in the most recent time period is mainly attributed to detection and removal of precancerous lesions through screening {13}.

Regarding tends in CRC mortality, according to Eurostat data {15}, average mortality rates from CRC in 25 EU member-states fell from 22.2 per 100,000 population in 2000 to 20.5 per 100,000 in 2010. Inequalities, however, exist between European countries also in CRC mortality trends. Mortality rates decreased since the mid-1990s for men and women almost in all countries, the exceptions been Croatia, Poland, Lithuania (men), Slovenia (men) and Spain (men) {12}. The least favourable trends in those countries (in which CRC mortality was lowest in the past) probably reflect a convergence of lifestyle and dietary habits towards those in other European countries {16}. Tends in mortality rates reflect the effect of cancer care, screening and diagnosis as well as changes in incidence {17} .

Regarding CRC survival, data from the EUROCARE rounds have revealed  improvements in average survival in the long-term {18}, {11}, {19}. Disparities in survival rates observed in earlier rounds seemed to narrow {7}. An analysis of data from 25 cancer registries in 16 European countries covering years of diagnosis from 1984 to 2002 {20}, concluded that for time periods from 1988–1990 to 2000–2002, CRC survival substantially increased over time in all European regions under study[1] and for both sexes. Increase in survival was observed also for all age groups (15–59, 60–74 and 75+ years), with the exception of Eastern European countries were 5-year relative survival in those over 75 years fell. However, the increase in survival was less pronounced for older patients (75+ age group) than for younger ones (aged 15–59 and 60–74) in all other European regions except Central Europe. Data from six countries in which registries included information on site and stage of diagnosis suggest that survival benefits were also larger for patients in earlier than in more advanced cancer stages and for rectum than for colon cancer. However, the substantial variation of CRC survival between European countries that was observed in earlier EUROCARE studies (highest levels of 5-year relative survival in Central and Northern Europe, followed by South European countries and UK and England, and lowest levels in Eastern Europe), were found to have persisted.

Differences in survival and trends over time depend on several reasons including increased access to more effective treatment, better management of co-morbidity, treatment being more effective due to earlier diagnosis, and lead-time bias or over diagnosis {21}, {10}. During the last two decades both early detection and treatment of CRC have improved {15), {22}. Accuracy and utilization of diagnostic technologies have increased as well as awareness among patients and primary care physicians {20}. Technological advances in the treatment and perioperative care of CRC (for example adjuvant chemotherapy, new surgical techniques, preoperative radiotherapy) that became available have also contributed to improvements in CRC survival {22, 23}.

In the framework of EUROCARE, high resolution studies were undertaken in an effort towards interpreting the impact of the aforementioned factors. The rationale adopted is that, if survival differences persist after adjustment for stage at diagnosis, there is evidence to suggest that differences in treatment significantly affect survival {21}. These studies brought forward the impact on CRC survival of (between and within countries) variations in  disease stage at diagnosis as well as variations in availability and use of effective diagnostic technologies and treatments {24-26} as referenced in {10}).

In the future, the number of new cases and deaths related to CRC are expected to increase. In specific, the International Agency on Research for Cancer (IARC) estimates the number of new CRC cases in Europe (in all ages) to rise to 502,000 in 2020, whereas the annual deaths from CRC in Europe are expected to rise to 248,000 {6}.

 

Burden of disease and Quality of life

According to WHO estimations {27}, in 2004, cancers were responsible for 151,461,000 Disability Adjusted Life Years (DALYs) in the European Region (11.3% of total DALYs). Trachea/bronchus/lung cancers, CRC and breast cancer were the main contributors, accounting for 19.1%, 11.1% and 10.2% of total DALYs due to cancer. Analysing the two components of DALYs, premature mortality was the main component for all cancer sites. DALYs in the European Region are projected to decrease to 116,729,000 in 2030, mainly due to the shift in age at death to older ages. The burden of disease due to CRC is estimated to follow this trend and decrease to 1,862,000 DALYs, corresponding to 11.7% of the total cancer burden.

Taking into consideration that both cancer and its treatment affect the physical and psychosocial condition of patients, policy-makers have been increasingly interested in evaluating the impact of cancer on patients' and survivors' quality of life (QoL) {28}. Until recently, there has been little research on the effects of long-term (≥5 years) survival from colon cancer on survivors' health status {29, 30}. Available evidence relates mainly to studies on patients during the treatment phase or the first years after diagnosis {31, 11}. Cross-sectional studies have shown that during the early years of diagnosis and treatment, CRC patients have poorer outcomes in terms of QoL, productivity losses and self-rated health than similar individuals with no history of cancer. They also report higher levels of psychological disability and problems with activities of daily living than controls {32,33,28, 34}.

In long-term (≥5 years) CRC survivors considered as cured (without recurrence or metastasis), overall QoL is similar to that of the general population; nevertheless, specific physical and psychosocial problems such as fatigue, dyspnea, insomnia,  bowel problems and deficits in emotional and social functioning persist over time and are also reported by survivors even 10 years after diagnosis {35,29, 36,37,38}.

In a prospective population-based cohort study from Germany {30}, long-term development of QoL depended on age at diagnosis. Younger survivors were found to report continuously substantial deficits in role, cognitive, emotional, and social functioning as well as presence of long-lasting symptoms in comparison to controls throughout the study period. In older survivors QoL was comparable to that of the general population during the first (1 to 3) years after diagnosis, however, QoL dimensions related to functioning, symptoms and problems worsened significantly between 3 and 10 years after diagnosis which suggests that detriments in older survivors become apparent in the long run. Global QoL scores of survivors were comparable to population norms regardless of duration of follow-up and despite the presence of limitations.

 

  [1] Northern Europe: Sweden, Norway, Finland, Iceland; Southern Europe: Italy, Slovenia; Central Europe: Austria, France, Germany, the Netherlands, Switzerland; Eastern Europe: Poland,  Slovakia; UK: Scotland, England, Wales.

 

As was noted, not all countries maintain population and cancer registers, therefore detailed comparisons are difficult. Data on incidence and mortality were extracted from the database of the GLOBOCAN project (International Agency for Research on Cancer), which provides contemporary estimates of these measures {6}. The most recent estimates are for 2008. Incidence data also derive from population-based cancer registries. More information on the GLOBOCAN data and sources are available on the project’s website. Regarding CRC survival, results of the EUROCARE project were preferred as it is a projects that aims to describe and interpret differences in cancer patient survival in Europe. However, there are limitations to the project, already acknowledged by the researchers {21}. The reader should keep in mind that not all European countries are involved in the EUROCARE project. Furthermore, for several countries cancer registration covers only a fraction of the total national population. The first round (EUROCARE-1) included 30 cancer registry populations diagnosed from 12 European countries. During the rounds that followed more regional and national registries participated. The current, fifth round (EUROCARE-5) includes data from 116 Cancer Registries in 30 European countries and for patients diagnosed during 2000-2007 {39}. Strengths, limitations and the value of findings are discussed in detail by the researchers {21, 40}.

Critical
Partially
Huic M et al. Result Card CUR9 In: Huic M et al. Health Problem and Current Use of the Technology In: Jefferson T, Cerbo M, Vicari N [eds.]. Fecal Immunochemical Test (FIT ) versus guaiac-based fecal occult blood test (FOBT) for colorectal cancer screening [Core HTA], Agenas - Agenzia nazionale per i servizi sanitari regionali; 2014. [cited 16 June 2021]. Available from: http://corehta.info/ViewCover.aspx?id=206

References