Faecal occult blood testing (FOBT) as screening for colorectal cancer: the current controversy

P. Boyle

Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy

Colorectal cancer is the fourth most common form of cancer that occurs worldwide, with an estimated 782 900 new cases diagnosed in 1990 [1]. The disease is not uniformly fatal, although there are large differences in survival according to the stage at which the disease is detected. In advanced colorectal cancer in which curative resection is possible, 5-year survival in Dukes’ B is 45%, dropping to 30% in Dukes’ C [2]. Five year survival in resected Dukes’ A is ~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%. Although it has been argued that death from colorectal cancer may be avoidable [3], it is estimated that there are still 394 000 deaths from colorectal cancer annually worldwide [4].

The identification of a well-defined pre-malignant lesion, the adenomatous polyp, together with the good survival associated with early disease, make colorectal cancer an ideal target for screening. In the past quarter of a century, great progress has been made in our ability to screen patients for colorectal cancer or its precursor state, using advances in imaging and diagnostic technology. Winawer [5] noted that Greegor [6] had first employed the faecal occult blood guaiac test cards, that the flexible sigmoidoscope was introduced in the mid-1970s to replace the rigid sigmoidoscope that had been first introduced in 1870 and that colonscopy has been available since 1970 [7].

Four randomised trials have examined annual or biennial screening with faecal occult blood testing (FOBT), whereas there are only early data available regarding sigmoidoscopy and colonoscopy, and little as yet from randomised trials. There is evidence from these randomised trials to support the use of FOBT [810], with a reduction in colorectal cancer mortality of ~16% [95% confidence interval (CI) 7% to 23%] from a meta-analysis [23% (95% CI 11% to 43%) reduction among those screened] [11] and a reduction in incidence reported, but only after 18 years of follow-up [12]. Concerns remain about the high level of false-positive results, the feasibility and the small clinical benefit of such screening. These concerns were recently outlined [13] and it was calculated that 1173 individuals needed to be tested for 10 years to avoid one death from colorectal cancer.

Various organisations have considered recommendations for colorectal cancer screening. A report to the Europe Against Cancer Advisory Committee on Cancer Prevention [14] recommended that ‘FOBT should be seriously considered as a preventive measure’. In an accompanying editorial, Coebergh [15] was not completely convinced by this report, pointing out that the modest effects seen could be due to the more intensive follow-up of controls in some of the trials [16].

Subsequently, some important findings have been reported. Lieberman and Weiss. [17] examined the sensitivity of FOBT and sigmoidoscopy for detecting neoplasia. Asymptomatic subjects (2885) provided stool specimens on cards, which underwent rehydration. They then underwent colonoscopy with sigmoidoscopy, defined as examination of the rectum and sigmoid colon during colonoscopy. Of subjects with advanced neoplasia, 23.9% had a positive test for occult blood. Compared with subjects who had a negative test for faecal occult blood, the relative risk of advanced neoplasia in subjects who had a positive test was 3.5 (95% CI 2.8, 4.4). Sigmoidoscopy identified 70% of all subjects with advanced neoplasia. Combined FOBT and sigmoidoscopy identified 75.8% of subjects with advanced neoplasia. The authors concluded that one-time screening with both FOBT (with rehydration) and sigmoidoscopy fails to detect advanced colonic cancer in 24% of subjects with the condition [17].

Detsky [18] considered that there are five important reasons why colonscopy is not routinely recommended as a screening tool: the standard of evidence, adherence, risk, economics and availability. The issue of standard of evidence is one that requires much attention in epidemiology at the present time. FOBT has been evaluated in randomised trials, whereas colonoscopy has not. Detsky [18] concluded that the higher sensitivity of colonoscopy plus the evidence that early detection improves survival is sufficient to conclude that colonoscopy is more effective than FOBT. In addition, there is support from observational studies.

There are some extremely important issues to address in the area of colorectal cancer screening. Should FOBT now be recommended as a population screening method? Should consideration be given to other screening modalities for colo-rectal cancer? Since a large proportion of individuals tested for FOB have positive tests and are referred for colonoscopy, could it prove effective to bypass FOBT and go directly to a screening colonoscopy? Or flexible sigmoidoscopy? This latter strategy is currently being assessed in a large, randomised trial and it is a clear reflection of the tremendous potential for the early detection of colorectal cancer by screening, which is clearly outlined in detail elsewhere [19].

Annals of Oncology has previously addressed such topical issues, notably the issue of prostate-specific antigen testing for prostate cancer [2025]. To bring all the arguments about colorectal cancer screening with FOBT to the readership, 12 international groups were invited to outline their position: eight accepted immediately and four declined to do so (on the grounds of pressing priorities). The groups were chosen for their expertise in the area of colorectal cancer; groups who have been involved in trials of colorectal cancer screening were excluded from consideration.

One common thread in all these articles relates to the economics of FOBT. La Vecchia [26] outlines the basic epidemiological data, both from observational studies and randomised trials, and indicates where there are key gaps in knowledge. McArdle [27] notes key issues such as compliance among deprived members of communities and the utility of two pilot studies on-going in the UK at the present to address such issues.

Lowenfels [28] invites the reader to reflect on the question: ‘Why don’t we screen for this potentially preventable cancer?’, emphasising that this is a major practical issue. He lays out the arguments in an epidemiological manner as to why screening is necessary and why FOBT may not be the best test, and weighs the potential benefits of other tests. The other gastroenterologists, Bleiberg [29], Crespi and Lisi [30], and Strul and Arber [31] have a more clinical approach and present good overviews and interpretations of the data available. Strul and Arber also give an interesting glimpse of new stool-based tests that may soon be available for population assessment and use.

Autier [32] and Barry [33] take a broader public health perspective. Arguing that FOBT produces modest changes in mortality rates, Autier concludes that FOBT is less efficient than screening tests for other cancers, such as Pap smear for cervix cancer and mammography for breast cancer [32]. Barry points out that ‘most Americans have not been screened for colorectal cancer by any means’, and the situation is identical throughout the rest of the world [33]. Unfortunately, as Barry emphasises, there is a gap between what the (public health) doctor prescribes and what the patient is willing to do. While this situation persists, and scientific squabbles continue about the best way to screen populations for colorectal cancer, the chance is being missed to prevent a significant number of the 400 000 colorectal cancer deaths that occur each year throughout the world.

I greatly enjoyed reading the expert opinions proposed by the authors of the articles in this issue [2633], and it is quite important to note both the similarities in the assessments and also the differences in the conclusions that are reached based on the same evidence. Consensus is an interesting, and frequently very useful, process, but sometimes a variety of viewpoints can give depth of insight. It is clear that there is a wide range of opinions about recommendations regarding the introduction of FOBT, or indeed any other test, as a popula-tion screening method for colorectal cancer.

This is not the end of the story. Eight opinions out of the hundreds potentially available does not constitute a random sample by any means. Annals of Oncology recognises the colorectal cancer screening debate as one of the most current in oncology and public health. To encourage this debate, we invite those interested to reply (in less than 1000 words) to the debate engaged above. These replies will be considered for publication in Annals of Oncology using an accelerated review process.

Acknowledgements

It is a pleasure to acknowledge that this work was conducted within the framework of support from the Associazione Italiana per la Ricerca sul Cancro (Italian Association for Research on Cancer).

P. Boyle

Division of Epidemiology and Biostatistics, European Institute of Oncology, Milan, Italy

References

1. Parkin DM, Whelan S, Ferlay J et al. (eds). Cancer Incidence in Five Continents. Volume VII. Lyon: IARC Sci Publ 1997.

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

3. Boyle P. Progress in preventing death from colorectal cancer. Br J Cancer 1995; 72: 528–530.[ISI][Medline]

4. Pisani P, Parkin DM, Bray F, Ferlay J. Estimates of the worldwide mortality from 25 major cancers in 1990. Int J Cancer 1999; 83: 18–29.[ISI][Medline]

5. Winawer SJ. A quarter century of colorectal cancer screening: progress and prospects. J Clin Oncol 2001; 19 (18 Suppl): 6S–12S.[ISI][Medline]

6. Greegor DH. Diagnosis of large-bowel cancer in the asymptomatic patient. JAMA 1967; 201: 943–945.[Medline]

7. Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; 112: 594–642.[ISI][Medline]

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. N Engl J Med 1993; 328: 1365–1371.[Abstract/Free Full Text]

9. 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.[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.[ISI][Medline]

11. 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, hemocult. BMJ 1998; 317: 559–565.[Abstract/Free Full Text]

12. 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]

13. Canadian Task Force on Preventive Health Care. Colorectal cancer screening. Recommendation from the Canadian Task Force on Preventive Health Care. Can Med Assoc J 2001; 165: 206–208.[Free Full Text]

14. Advisory Committee on Cancer Prevention. Recommendations on cancer screening in the European Union. Eur J Cancer 2000; 36: 1473–1478.[ISI][Medline]

15. Coebergh JW. Challenges and pitfalls of mass-screening in the European Union. Eur J Cancer 2000; 36: 1469–1472.[ISI][Medline]

16. Faivre J, Tazi MA, Autier P, Bleiberg H. Should there be mass screening using faecal occult blood tests for colorectal cancer? Eur J Cancer 1998; 34: 773–780.[ISI][Medline]

17. Lieberman DA, Weiss DG. One-time screening for colorectal cancer with combined fecal occult-blood testing and examination of the distal colon. N Engl J Med 2001; 345: 555–560.[Abstract/Free Full Text]

18. Detsky A. Screening for colon cancer—can we afford colonoscopy? N Engl J Med 2001; 345: 607–608.[Free Full Text]

19. Mandel JS. Colon and rectal cancer. In Reintgen DS, Clark RA (eds): Cancer Screening. St Louis, MO: Mosby 1996; pp. 55–96.

20. Boyle P. Prostate specific antigen (PSA) testing as screening for prostate cancer: the current controversy. Ann Oncol 1998; 9: 1263– 1264.[ISI][Medline]

21. Zappa M, Ciatto S, Bonardi R, Mazzotta A. Overdiagnosis of pros- tate carcinoma by screening: an estimate based on the results of the Florence Screening Pilot Study. Ann Oncol 1998; 9: 1297–1300.[Abstract]

22. Barry MJ. PSA screening for prostate cancer: the current controversy—a viewpoint. Patient Outcomes Research Team for Prostatic Diseases. Ann Oncol 1998; 9: 1279–1282.[Abstract]

23. Svetec D, Thompson IM. PSA screening—current controversy. Ann Oncol 1998; 9: 1283–1288.[Abstract]

24. de Koning HJ, Schroder FH. PSA screening for prostate cancer: the current controversy. Ann Oncol 1998; 9: 1293–1296.[ISI][Medline]

25. Neal DE, Donovan JL. Screening for prostate cancer. Ann Oncol 1998; 9: 1289–1292.[ISI][Medline]

26. La Vecchia C. Fecal occult blood screening for colorectal cancer: open issues. Ann Oncol 2002; 13: 31–34.[Abstract/Free Full Text]

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

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

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

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

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

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

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