Workgroup I: criteria for screening. UICC International Workshop on Facilitating Screening for Colorectal Cancer, Oslo, Norway (29 and 30 June 2002)

P. Boyle1,{dagger}, H. Vainio1,{dagger}, R. Smith2,{ddagger},*, R. Benamouzig3, W. C. Lee4, N. Segnan5, K. Takima6 and Y. Tsubono7

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


    Introduction
 Top
 Introduction
 Colorectal cancer control
 Criteria for screening
 Criteria, guidelines and...
 Conclusions
 References
 
While there are many questions to be resolved, it is apparent that the biology of colorectal neoplasia is becoming increasingly understood, and prospects for prevention are becoming a reality. Achieving colorectal cancer control is an immediate challenge and should be approached in a positive frame of mind given that death from colorectal cancer frequently can be prevented if the disease is detected at an early stage [1Go].

Colorectal cancer is the fourth most common form of cancer occurring worldwide, with an estimated 1.02 million new cases diagnosed in 2002 [2Go], 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) [2Go].



View larger version (22K):
[in this window]
[in a new window]
 
Figure 1. Incidence of colorectal cancer: age-standardized rate (world), male (all ages).

 


View larger version (22K):
[in this window]
[in a new window]
 
Figure 2. Incidence of colorectal cancer: age-standardized rate (world), female (all ages).

 
This pattern of disease has led to the impression that colorectal cancer is a ‘Western lifestyle’ disease [3Go]. However, although colorectal cancer is a greater cause of morbidity in Western lifestyle countries, the majority of the world's cases of colorectal cancer in both men and women occur outside of countries in which traditional Western lifestyles are dominant.

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) [4Go]. Using the information from around the world in 2002 [2Go], 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 [5Go]. 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.



View larger version (24K):
[in this window]
[in a new window]
 
Figure 3. Colorectal cancer mortality in Japan, 1950–1999.

 


View larger version (14K):
[in this window]
[in a new window]
 
Figure 4. Colorectal cancer mortality in Korea, 1983–2000.

 

    Colorectal cancer control
 Top
 Introduction
 Colorectal cancer control
 Criteria for screening
 Criteria, guidelines and...
 Conclusions
 References
 
Prospects for prevention of colorectal cancer death are more favorable than for many cancers [6Go]. Recommendations to establish screening programmes for colorectal cancer come from a variety of sources, principally based on the observation that disease outcomes are significantly improved when the disease is treated at an early stage, and through the demonstrated efficacy of screening tests.

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 [7Go]. 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 [2Go].

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 [8Go–11Go]. A meta-analysis of all three studies produced a relative risk of colorectal cancer death of 0.84 (95% confidence interval 0.77–0.93) [12Go]. 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 [8Go], 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 [13Go]. These findings and others are important confirmation that Haemoccult screening may be effective in the prevention of death from colorectal cancer [14Go–21Go].

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 [22Go–24Go]. 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 [25Go]. 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.


    Criteria for screening
 Top
 Introduction
 Colorectal cancer control
 Criteria for screening
 Criteria, guidelines and...
 Conclusions
 References
 
Wilson and Jungner [26Go] established a series of criteria that should ideally be fulfilled before considering screening as a public health policy (Table 1). The decision to screen is not based on any single dimension (e.g. extent of the public health problem, magnitude of the benefit, cost), but on a careful evaluation of the multidimensionality of the issues.


View this table:
[in this window]
[in a new window]
 
Table 1. Screening criteria of Wilson and Junger [26Go]

 
1. Is the disease an important public health problem?
In the world, colorectal cancer is the second most common form of cancer in women and the third most common form in men, and this disease is no longer restricted to countries with Western lifestyle. Risk is rising quickly in many countries previously considered to be at low risk. However, even within low-risk populations there may be identifiable subgroups at higher risk.

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 [25Go, 27Go].

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). Case–control 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 [28Go, 29Go].

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 [30Go].

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 [31Go, 32Go].

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 [33Go–35Go]. 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.


    Criteria, guidelines and evaluation
 Top
 Introduction
 Colorectal cancer control
 Criteria for screening
 Criteria, guidelines and...
 Conclusions
 References
 
Clearly, colorectal cancer screening fulfils the WHO criteria by a comfortable margin. In order to proceed with colorectal cancer screening, agreed guidelines need to be in place, as does the capacity to deliver the program and assure follow-up when necessary (see Table 2).


View this table:
[in this window]
[in a new window]
 
Table 2. Areas where guidelines are required

 
Minimum guidelines require that there should be a list of the target population available, whether at a national, regional or practice level. There needs to be an established infrastructure for diagnosis and treatment and a program for training of health-care professionals. Follow-up is essential and the cancer registry would be an important partner. Screening programs will identify a series of individuals at high risk of colorectal cancer by reasons of hereditary (e.g. familial adenomatous polyposis, hereditary non-polyposis colon cancer), or non-familial factors, and programs need to be equipped with an infrastructure and resources to identify, counsel and follow-up these subgroups.

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.


View this table:
[in this window]
[in a new window]
 
Table 3. Evaluation of screening program

 

    Conclusions
 Top
 Introduction
 Colorectal cancer control
 Criteria for screening
 Criteria, guidelines and...
 Conclusions
 References
 
Colorectal cancer is the fourth most common form of cancer diagnosed worldwide. It causes over half a million deaths annually, and is a disease that is no longer restricted to Western countries. There is adequate evidence that screening for colorectal cancer, conducted in a setting with good quality assurance, can significantly reduce the mortality rates from this disease.

Screening has an important role to play in any program of colorectal cancer control. The criteria of the WHO [26Go] 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.


    Notes
 
{dagger} Co-chairs Back

{ddagger} Rapporteur Back


    References
 Top
 Introduction
 Colorectal cancer control
 Criteria for screening
 Criteria, guidelines and...
 Conclusions
 References
 
1. Boyle P. Progress in preventing death from colorectal cancer. Br J Cancer 1995; 72: 528–530.[ISI][Medline]

2. Ferlay J, Bray F, Pisani P, Parkin DM. Globocan 2002: Cancer Incidence, Mortality, and Prevalence Worldwide. IARC Cancerbase No. 5, version 2.0. IARC Press, Lyon 2004.

3. Muir CS, Nectous J. International patterns of cancer. In Schottenfeld D, Fraumeni JF Jr (eds): Cancer Epidemiology and Prevention. New York: Oxford University Press 1996; 141–167.

4. Parkin DM, Whelan S, Ferlay J et al. Cancer Incidence in Five Continents, Vol. VII. IARC Scientific Publications, Vol. 143. Lyon: IARC Press 1997.

5. Boyle P, Golia S, Daly P et al. Cancer mortality in Ireland, 1926-1995. Ann Oncol 2003; 14: 323–332.[Abstract/Free Full Text]

6. Zaridze DG. Environmental etiology of large-bowel cancer. J Natl Cancer Inst 1983; 70: 389–400.[ISI][Medline]

7. Morson BC. Gastrointestinal Pathology. Oxford: Blackwell Scientific Publications 1979.

8. Mandel JS, Bond JH, Church TR et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study [published erratum appears in N Engl J Med 1993; 329 672]. N Engl J Med 1993; 328: 1365–1371.[Abstract/Free Full Text]

9. Kewenter J, Brevinge H, Engaras B et al. Follow-up after screening for colorectal neoplasms with fecal occult blood testing in a controlled trial. Dis Colon Rectum 1994; 37: 115–119.[ISI][Medline]

10. Hardcastle JD, Chamberlain JO, Robinson MH et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996; 348: 1472–1477.[CrossRef][ISI][Medline]

11. Kronborg O, Fenger C, Olsen J et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996; 348: 1467–1471.[CrossRef][ISI][Medline]

12. Towler B, Irwig L, Glasziou P et al. A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, haemoccult. BMJ 1998; 317: 559–565.[Abstract/Free Full Text]

13. Mandel JS, Church TR, Bond JH et al. The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000; 343: 1603–1607.[Abstract/Free Full Text]

14. McArdle CS. Faecal occult blood testing for colorectal cancer. Ann Oncol 2002; 13: 35–39.[Free Full Text]

15. Lowenfels AB. Fecal occult blood testing as a screening procedure for colorectal cancer. Ann Oncol 2002; 13: 40–43.[Free Full Text]

16. Bleiberg H. Haemoccult should no longer be used for the screening of colorectal cancer. Ann Oncol 2002; 13: 44–46.[Free Full Text]

17. Crespi M, Lisi D. Is colorectal cancer screening by fecal occult blood feasible? Ann Oncol 2002; 13: 47–50.[Free Full Text]

18. Strul H, Arber N. Fecal occult blood test for colorectal cancer screening. Ann Oncol 2002; 13: 51–56.[Free Full Text]

19. Autier P. Should organised faecal occult blood test screening be established? Ann Oncol 2002; 13: 57–60.[Abstract/Free Full Text]

20. Barry MJ. Fecal occult blood testing for colorectal cancer: a perspective. Ann Oncol 2002; 13: 61–64.[Abstract/Free Full Text]

21. Boyle P. Faecal occult blood testing (FOBT) as screening for colorectal cancer: the current controversy. Ann Oncol 2002; 13: 16–18.[Free Full Text]

22. Gilbertsen VA, Nelms JM. The prevention of invasive cancer of the rectum. Cancer 1978; 41: 1137–1139.[ISI][Medline]

23. Selby JV, Friedman GD, Quesenberry CPJ, Weiss NS. A case-control study of screening sigmoidoscopy and mortality from colorectal cancer. N Engl J Med 1992; 326: 653–657.[Abstract]

24. Newcomb PA, Norfleet RG, Storer BE et al. Screening sigmoidoscopy and colorectal cancer mortality. J Natl Cancer Inst 1992; 84: 1572–1575.[Abstract]

25. Winawer SJ, Zauber AG, Ho MN et al. Prevention of colorectal cancer by colonoscopic polypectomy The National Polyp Study Workgroup. N Engl J Med 1993; 329: 1977–1981.[Abstract/Free Full Text]

26. Wilson JMG, Junger G. Principles and Practice of Screening for Disease. Geneva: WHO 1968.

27. Stryker S, Wolff B, Culp C et al. Natural history of untreated colonic polyps. Gastroenterology 1987; 93: 1009–1013.[ISI][Medline]

28. Glick S, Wagner JL, Johnson CD. Cost-effectiveness of double-contrast barium enema in screening for colorectal cancer. AJR Am J Roentgenol 1998; 170: 629–636.[ISI][Medline]

29. Winawer SJ, Stewart ET, Zauber AG et al. A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. The National Polyp Study Workgroup. N Engl J Med 2000; 342: 1766–1772.[Abstract/Free Full Text]

30. Vernon SW. Participation in colorectal cancer screening: a review. J Natl Cancer Inst 1997; 89: 1406–1422.[Abstract/Free Full Text]

31. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell 1990; 61: 759–767.[ISI][Medline]

32. Vogelstein B, Fearon ER, Hamilton SR et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988; 319: 525–532.[Abstract]

33. Kronborg O. Population screening for colorectal cancer, the goals and means. Ann Med 1991; 23: 373–379.[ISI][Medline]

34. Wagner JL, Tunis J, Brown M, et al. Cost-effectiveness of colorectal cancer screening in average-risk adults. In Young G, Levin B (eds): Prevention and Early Detection of Colorectal Cancer. London: Saunders 1996; 321–356.

35. Frazier AL, Colditz GA, Fuchs CS, Kuntz KM. Cost-effectiveness of screening for colorectal cancer in the general population. JAMA 2000; 284: 1954–1961.[Abstract/Free Full Text]





This Article
Full Text (PDF)
E-letters: Submit a response
Alert me when this article is cited
Alert me when E-letters are posted
Alert me if a correction is posted
Services
Email this article to a friend
Similar articles in this journal
Similar articles in ISI Web of Science
Similar articles in PubMed
Alert me to new issues of the journal
Add to My Personal Archive
Download to citation manager
Search for citing articles in:
ISI Web of Science (2)
Disclaimer
Request Permissions
Google Scholar
Articles by Boyle, P.
Articles by Tsubono, Y.
PubMed
PubMed Citation
Articles by Boyle, P.
Articles by Tsubono, Y.