Burden of Disease

CRC is the fourth most common cancer in the world with approximately 1 000 000 new cases per year worldwide (GLOBOCAN 2002). CRC accounts for 10% of all cancer. North America, Australia/New Zealand and Europe are considered to be high-risk areas. Colon cancer is more common in developed countries exhibiting westernised lifestyle practices.

In general, the incidence of CRC is increasing rather rapidly in countries where the overall risk was formerly low (especially in Japan, but also elsewhere in Asia). In high-risk countries, the trends are either gradually increasing, stabilising (North and West Europe) or declining with time (North America). Such changes over time have been noted particularly in younger age groups [3, 7,17, 35].

CRC is not perceived as a significant health problem in developing countries, where infectious disease and perinatal and maternal mortality have usually received more attention. However, once an individual has survived the first five years of life, cancer becomes one of the major causes of death in developing countries [36]. The slow, but progressive, extension to developing countries of western culture and the ageing of the population will lead to an increase in the incidence of the neoplasm in these countries.

In the last few decades, the increase has been more relevant in Eastern than in Western populations. The incidence of CRC in the Czech Republic is one of the highest in Europe and the incidence of rectal cancer is the highest in Europe in both male and females [9, 13,15, 37-40].

Even if the age-specific mortality rates remain constant between 2000 and 2004, there will be an increase in the absolute number of cancer cases and deaths in the foreseeable future. Although the total population will remain fairly constant, compared with 2000, by 2015 there will be a 22% increase in the population aged >65 years and a 50% higher number of persons aged >80 years [38]. Given the association between CRC risk and age, this will lead to a major increase in the cancer burden [41].

Analysis of trends in all cancer mortality in Europe over the past 30 years has shown that after long-term rises, age-standardised mortality from most common cancer sites has fallen in the European Union since the late 1980s. In the 1980s, the 12 member-countries of the European Community set the ambitions target to reduce cancer mortality from 15% between 1985 and 2000. The actual overall decrease was 10% in men and 8% in women [42]. The target was met only in Austria and Finland, for both men and women; in Luxembourg and the UK there were 15% reductions in men, but not in women. In Greece and Portugal there was an increase in the numbers of cancer deaths in both sexes.

Cancer incidence can measure the effect of primary prevention but not of early detection. The latter may cause an increase in incidence, which occurred in several countries using breast screening mammog-raphy. The aim of early detection is to improve survival. Cancer mortality reflects the combined effects of changes in incidence and survival [38].

Rising trends in risk of dying from CRC are present in the majority of European Union member states and there are particularly strong trends in increasing risk in Spain, Portugal and Greece [41].

Interestingly, there has been a striking decline in CRC in women compared with men. This may in part be due to the increasing penetration of oral contraceptives and, particularly, hormone replacement therapy (HRT) [43], both of which have consistently been associated with a decreased risk of CRC. However, this may be sheer speculation. There has been an overview of all the case-control and cohort studies investigating this association separately for oral contraceptive and HRT users. Overall, the risk of CRC in users of oral contraceptives (compared with never-users) was reduced by 18% [RR=0.82, 95% confidence interval (CI) 0.74-0.92] [44]. For HRT, the risk of CRC was reduced, overall, by 20% among users compared with non-users (RR=0.8, 95% CI 0.78-0.82) [45].

Screening for CRC has been shown to be effective [42]. The introduction of organised screening pro-

Table 4. Staging (% of total) and 5-year survival of colorectal carcinoma, by anatomical sub-localisation UICC Disease stage at time of diagnosis 5-year survival rate %

Colon Rectum Colon Rectum

Unknown

25-30 20-30 12-20 13

grammes throughout Europe will lead to a reduction in CRC mortality. The maximum effect will be derived from programmes with effective quality control procedures in place.

CRC, with an estimated 376 400 new cases and 203 700 deaths in 2004, remains an important public health problem in Europe. Even if age-specific rates remain constant, the ageing of the European population will cause these numbers to continue to tise.

In its Annual Report, the American Cancer Society estimates that, in 2005 in the United States, about 145 290 people will be diagnosed with CRC, and that about 56 290 people will die from this disease [46]. In the United States, CRC is the third most common cancer both for men and women. The incidence ranks second to breast cancer for Hispanic, American Indian/Alaska Native and Asian/Pacific Islander women, and ranks third for white and black women [14]. The overall incidence increased until 1985, then began to decrease steadily at an average rate of 1.6% per year. For women, mortality rates have been declining since at least 1950, while rates for men remained fairly level from 1950 to 1980, but then began declining in the 1980s. The five-year relative survival rate for CRC was 61% and varied by stage. When CRC was detected in the earliest stage of the disease, Stage I, the survival rate was 96%, whereas survival for Stage IV was only 5%.

The Authors of the report suggested that screening and advances in treatment helped to reduce mortality from the disease. They also found that incidence and mortality varied somewhat from state to state. Incidence and mortality among African Americans was higher than in other racial and ethnic groups, a disparity which could possibly be reduced in the future through better screening utilisation and access to care.

From 1990 to 1994 the survival rate of subjects with rectal cancer in Europe was 75% at one year and 47% at five years. The five-year relative survival rate declined with age: from 55% in the youngest (45-54 years) to 39% in the oldest age group of patients (75 years and over) [40, 47]. There have been consistent improvements in the survival rate since the late 1970s in both sexes and in all regions of Europe. In Europe as a whole, survival rates rose by 7% for both one and five-year survival [40]. The survival curves for rectal cancer differ in shape from colon cancer. The one-year survival rate from rectal cancer is higher than colon cancer (75 vs. 70%), but the five-year survival rate is similar (Table 4).

In the United States, the 5-year survival rate for patients diagnosed with cancer of the rectum during 1985-89 was 57%, while in Europe the figure was 43% [5]. Rectal cancer is characterised by a much better response when treated at an early stage. The large survival differences may therefore, reflect the fact that more healthy Americans than Europeans undergo early diagnostic procedures. An indicator of early diagnosis is the proportion of CRCs that are diagnosed as adenocarcinomatous polyps; this figure was much higher among American cases than in European cases (13% vs. 2%) [12].

The EUROCHIP study demonstrated that CRC patients' incidence and survival depends on socioeconomic factors including access to and quality of medical care [48]. In the EUROCHIP study, gross domestic product (GDP), total (public and private) health expenditure (HE) and longer survival rates in CRC were significantly correlated, indicating that the availability of resources can influence the clinical outcomes (Fig. 3).

In fact, in these countries, with lower GDPs and HEs, there are also lower incidence and mortality rates for CRC. In Italy, it is lower yet again by a 5-year survival percent (Figs. 2-4 and Tables 5, 6). In countries with a GDP lower than 10 000 PPP$ (parity of purchasing power in US $) per capita such as Mexico, Venezuela, Botswana, Mauritius and the Dominican Republic, the incidence of new cases of CRC, both in men and women, is around 0.30 and 0.50 for every 100 000 people/year. On the other hand, countries with a GDP of more than 20 000 PPP$ per capita have, except for Finland, an age-standardized rate (ASR) incidence for CRC higher than 1.40 new cases for 100 000 people.

It is possible to suppose the existence of a direct relation between the number of new cases of CRC and the GDP per capita (ASR incidence and GDP per capita: correlation coefficient 0.63; p<0.0001; ASR

Fig. 2. Five-year survival for colorectal cancer and total health expenditure (HE) PPP US $ per capita (2002). Correlation coefficient 0.81; p<0.0001; R2=0.67

5-years survival for colorectal cancer {%)

5-years survival for colorectal cancer {%)

Fig. 2. Five-year survival for colorectal cancer and total health expenditure (HE) PPP US $ per capita (2002). Correlation coefficient 0.81; p<0.0001; R2=0.67

Fig. 3. Age standardised (world population) incidence rates for colorectal cancer and gross domestic product (GDP) PPP US $ per capita (2002). Correlation coefficient 0.63; p<0.0001; R2=0.40

40000-

Fig. 3. Age standardised (world population) incidence rates for colorectal cancer and gross domestic product (GDP) PPP US $ per capita (2002). Correlation coefficient 0.63; p<0.0001; R2=0.40

40000-

10000^

ASR(W) colorectal cancer mortality, 2002

Fig. 4. Age standardised (world population) mortality rates for colorectal cancer and gross domestic product (GDP) PPP US $ per capita (2002). Correlation coefficient 0.54; p<0.0001; R2=0.30

Table 5. Incidence and mortality age standardised rate (ASR) per 100 000 for colorectal cancer and gross domestic product (GDP) PPP US $ per capita (2002) in different countries

Country GDP Incidence ASR (W) Mortality ASR (W)

Table 5. Incidence and mortality age standardised rate (ASR) per 100 000 for colorectal cancer and gross domestic product (GDP) PPP US $ per capita (2002) in different countries

Country GDP Incidence ASR (W) Mortality ASR (W)

Mexico

8190

0.30

0.29

0.17

0.17

Venezuela

8190

0.46

0.46

0.25

0.25

Botswana

8310

0.25

0.17

0.21

0.13

Mauritius

9400

0.50

0.30

0.25

0.17

Dominican Republic

9440

0.46

0.50

0.25

0.26

Uruguay

9480

1.63

1.21

0.75

0.58

Argentina

10 200

1.25

0.79

0.59

0.38

Bahamas

10 460

0.63

0.59

0.34

0.34

Madagascar

10 530

0.25

0.17

0.25

0.13

Barbados

12 260

1.00

0.75

0.59

0.46

Korea, Republic

12 270

1.00

0.63

0.42

0.25

Chile

12 890

0.63

0.63

0.30

0.30

Greece

13 010

0.79

0.63

0.38

0.33

Malta

13 610

1.13

0.92

0.67

0.54

Bahrain

13 700

0.50

0.29

0.33

0.17

Portugal

14 380

1.50

0.88

0.83

0.46

New Zealand

15 840

2.21

1.75

0.96

0.75

Spain

16 060

1.51

0.92

0.75

0.46

Israel

17310

1.71

1.42

0.76

0.59

Ireland

18 340

1.79

1.13

0.96

0.55

Sweden

19 480

1.38

1.08

0.59

0.46

United Arab Emirates

19 720

0.50

0.46

0.30

0.29

Australia

20 130

1.96

1.46

0.75

0.54

Italy

20 200

1.63

1.09

0.67

0.42

Finland

20 270

1.05

0.88

0.46

0.38

United Kingdom

20 640

1.63

1.09

0.71

0.50

Germany

20 810

1.88

1.38

0.80

0.63

The Netherlands

21 620

1.67

1.26

0.76

0.59

France

22 320

1.67

1.05

0.75

0.46

Austria

22 740

1.75

1.13

0.83

0.55

Iceland

22 830

1.42

1.13

0.51

0.54

Japan

23 180

2.04

1.09

0.71

0.46

Belgium

23 480

1.54

1.09

0.75

0.58

Denmark

23 830

1.71

1.38

0.96

0.79

Canada

24 050

1.75

1.25

0.67

0.46

Norway

24 290

1.79

1.54

0.83

0.67

Switzerland

26 620

1.75

1.04

0.63

0.38

Singapore

28 620

1.46

1.21

0.80

0.67

United States of America

29 340

1.84

1.38

0.63

0.46

Luxembourg

37 420

1.80

1.26

0.75

0.54

mortality and GDP per capita: correlation coefficient 0.54; p<0.0001).

The same figure is shown considering the age-adjusted 5-year survival rate and the HE. And, in fact, there is a direct relation between the survival rate 5 years from diagnosis of CRC and the HE (correlation coefficient 0.82; p<0.0001).

The association between fiscal input and clinical outcomes should be taken into account for the development of effective public health. It can be argued that larger investments must translate into greater primary and secondary prevention and specialised care.

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