1 International Agency for Research on Cancer, Lyon, France; 2 American Cancer Research Society, Atlanta, GA, USA; 3 AP-HL Hopital Avicenne, Bobigny, France; 4 The Catholic University of Korea, Seoul, Korea; 5 Unita di Epidemiologia dei Tumori, Turin, Italy; 6 Aichi Cancer Research Institute, Nagoya, Japan; 7 Tohoku University Graduate School of Medicine, Sendai, Japan
* Correspondence to: Dr R. Smith, American Cancer Society, 1599 Clifton Road NE, Atlanta, GA 30329, USA. Tel: +1-404-329-7610; Email: robert.smith{at}cancer.org
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Introduction |
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Colorectal cancer is the fourth most common form of cancer occurring worldwide, with an estimated 1.02 million new cases diagnosed in 2002 [2], and an estimated 529 000 deaths. Colorectal cancer is most frequent in North America, Argentina, Australia, New Zealand, and parts of Europe, Japan and Israel (see Figures 1 and 2) [2
].
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Global, age-standardized rates of colorectal cancer (International Classification of Diseases codes 153 and 154) incidence are slightly higher in men than in women (20.1 and 14.6 per 100 000, respectively) [4]. Using the information from around the world in 2002 [2
], in men colorectal cancer comprised 9.5% of all cancers, 13.1% of all cancers in Western lifestyle countries and 6.3% in other countries. In women, colorectal cancer comprised 9.3% of all cancers, 13.5% of all cancers in Western lifestyle countries and 5.8% in other countries. Furthermore, the incidence of this malignancy shows considerable variation among racially or ethnically defined populations in multi-racial/ethnic countries.
Mortality rates from colorectal cancer in men and women in Western countries have remained relatively constant throughout the century [5]. However, there have been rapid changes in many countries previously considered low risk. For example, mortality rates have increased five-fold in Japan since 1950 (Figure 3) and four-fold in Korea since 1983 (Figure 4). Clearly, colorectal cancer is an important public health problem not only in Western lifestyle countries, but also increasingly in other parts of the world.
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Colorectal cancer control |
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Overall survival rates for colorectal cancer vary from 40% to 60%. In advanced colorectal cancer, when curative resection is possible, 5-year survival in Dukes B is 45%, and survival drops to 30% for Dukes C colorectal cancer [7]. However, 5-year survival in resected Dukes A is around 80%, and survival following simple resection of an adenomatous pedunculated polyp containing carcinoma in situ (or severe dysplasia) or intramucosal carcinoma is generally close to 100%. Despite this knowledge and apparent pathway to avoid colorectal cancer mortality, there are still 529 000 deaths from colorectal cancer worldwide annually [2
].
The large differences in survival between early- and late-stage disease clearly indicate the advantage in detecting colorectal cancer early. For disease that becomes symptomatic, the simplest advice is to ensure that any change in bowel habits or unexpected presence of blood in the stool should be investigated. Fecal occult blood testing (FOBT) is aimed at the detection of early asymptomatic cancer, and is based on the assumption that such cancers will bleed and that small quantities of blood lost in the stool may be detected chemically or immunologically. A significant reduction in colorectal cancer mortality with Haemoccult testing has been reported from three randomized controlled trials, one in the USA and two in Europe [811
]. A meta-analysis of all three studies produced a relative risk of colorectal cancer death of 0.84 (95% confidence interval 0.770.93) [12
]. The results are of considerable importance, although emphasis on FOBT as a simple, inexpensive screening test must also take into consideration the requirement to evaluate any positive screening test with colonoscopy. In the Minnesota trial [8
], 38% of those screened annually and 28% of those screened biennially underwent at least one colonoscopy during the study. A favorable observation associated with excess colonoscopy resulting from false-positive FOBT results is that polyps may be identified and removed. An important finding has been the demonstration that after 18 years there was a significant reduction in the incidence of colorectal cancer in subjects randomized to the Haemoccult arm of the Minnesota study [13
]. These findings and others are important confirmation that Haemoccult screening may be effective in the prevention of death from colorectal cancer [14
21
].
There is a good deal of evidence supporting infrequent sigmoidoscopy as a potentially effective screening modality for colorectal cancer, although results from randomized trials have not yet been reported. Impressive reductions in rectal cancer and cancer of the distal colon have been reported from epidemiological studies [2224
]. Although the initial examination may be expensive, there is the advantage that polyps in the distal bowel may be removed at the time of the initial procedure, and the use of colonoscopy can be restricted to those at increased risk of proximal neoplasia. At this time, use of a 65-cm flexible sigmoidoscope appears to be an effective strategy, since it can examine the area of the bowel where about half of colorectal neoplasias are detected.
Although colonoscopy is most commonly used for diagnostic investigation, screening with colonoscopy is becoming more frequent in some countries. Like sigmoidoscopy, there are no results available from randomized trials, and none are forthcoming since at present there is no randomized trial of screening with colonoscopy underway. However, the effectiveness of colonoscopy to examine the entire large bowel, and identify and clear polyps, is strongly supported from observational studies [25]. Both sigmoidoscopy and colonoscopy offer the possibility of reducing the incidence of colorectal cancer both by a greater magnitude and considerably more quickly than FOBT.
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Criteria for screening |
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2. Is there an effective treatment for localized disease?
Five-year survival in resected Dukes A is around 80% and survival following simple resection of an adenomatous pedunculated polyp containing carcinoma in situ (or severe dysplasia) or intramucosal carcinoma is close to 100%. The large differences in survival between early- and late-stage disease clearly indicate the advantage in detecting colorectal cancer at an early stage. Removal of polyps can be expected to lead to reductions in incidence of invasive cancers.
3. Are facilities for further diagnosis and treatment available?
It is essential to see screening as only one step in the global management of a patient with colorectal cancer. There are important lessons to be learned from mammographic screening, particularly that the best outcomes occur when the multidisciplinary diagnostic and treatment team is integrated with the screening programme.
4. Is there an identifiable latent or early symptomatic stage of disease?
Most invasive colorectal cancers arise from adenomatous polyps and this may well be the best biological marker of risk identified at the present time [25, 27
].
5. Is the technique to be used for screening effective?
FOBT, sigmoidoscopy, double-contrast barium enema and colonoscopy are all effective screening tools. Randomized trials demonstrate a reduction of colorectal cancer mortality (and incidence) in individuals randomized to invitation to FOBT screening (using Haemoccult). Casecontrol studies also demonstrate a benefit of both Haemoccult and immunological FOBT. One-time FOBT in the doctor's office obtained by digital rectal examination is an unproductive use of resources. There is evidence from observational studies that once-only sigmoidoscopy can reduce colorectal cancer incidence and mortality, and large randomized trials are underway. There is also evidence from observational studies that colonoscopy can reduce colorectal cancer incidence and mortality, and colonoscopy was integral to observed benefits, reductions in both mortality and incidence, in the Minnesota trial. Observational studies demonstrate that barium enema is associated with a reduction in mortality but it has lower sensitivity for important polyps and cancer than colonoscopy [28, 29
].
6. Are the tests acceptable to the population?
The participation rate in trials and organized (pilot) programs indicates that the FOBT and sigmoidoscopy are acceptable to a large proportion of the population, although the accumulated evidence indicates that there are variations in individual preferences for the different colorectal cancer screening tests [30].
7. Is the natural history of the disease known?
There is, arguably, a better understanding of the natural history of colorectal carcinogenesis than of any other solid tumor [31, 32
].
8. Is there a strategy for determining which patients should and should not be treated?
It is unthinkable to screen a volunteer, find a cancer and then offer no treatment. There need to be guidelines in place to describe the treatment modalities and follow-up after diagnosis.
9. Is the cost of screening acceptable?
The decision to make a large investment in a preventive health program is based on a balance of many considerations including scientific evidence, public pressure and political will. Screening for colorectal cancer has been shown to be cost-effective from a variety of studies [3335
]. However, rational decisions to spend money on screening cannot simply be based on costs or any other single dimension.
10. Screening should be an on-going process
Once a screening program is established it is essential to see it through (except in exceptional circumstances). It is not acceptable to offer screening to the public and then abandon the program or neglect attention to quality assurance and on-going program monitoring. Informed consent for an individual to participate in a screening program carries the implicit bargain that the program will continue until the benefit is evaluated.
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Criteria, guidelines and evaluation |
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Ideally, screening programs should be organized and population-based. However, there are regions where this is not available and there will be a certain amount of opportunistic screening available. However, it is essential that the same guidelines be applied to this form of screening, being particularly aware that an essential prerequisite for screening is to have quality assurance standards and practices in place, as well as established method available for monitoring and evaluation of these procedures in addition to the outcome of the screening programme. Guidelines for follow-up of cases are mandatory, as are guidelines about informed consent, counseling and follow-up of high-risk groups, treatment policy, diagnosis and reporting, and quality assurance. A key element of having quality assurance guidelines is that there is a procedure in place for their evaluation.
It is arguably unethical to set up a screening program without having an apparatus for evaluation in place. It is essential that several key pieces of information are available to evaluate the program (Table 3). These range from the participation rate, both overall and in relevant subgroups (i.e. the most deprived members of the community being screened, or high-risk groups), to indicators of outcome such as the overall incidence rate, the incidence rate of advanced disease, survival and ultimately death from colorectal cancer.
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Conclusions |
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Screening has an important role to play in any program of colorectal cancer control. The criteria of the WHO [26] are fulfilled and local and international guidelines can be developed. The Workgroup was of the opinion that there is little reason to continue to have meetings to discuss whether it is useful to screen for colorectal cancer and to continue to anguish over which test to use. It is clear that screening for colorectal cancer is useful and we have clear evidence of the utility of each of the tests. At this time, it is essential to understand that the best test is the one that is done, and, as far as implementing colorectal cancer screening programmes, the message is simple: Just Do It.
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Notes |
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References |
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