EDITORIALS

Colorectal Cancer Screening: Sifting Through the Evidence

Bernard Levin

Correspondence to: Bernard Levin, M.D., Division of Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Box 203, 1515 Holcombe Blvd., Rm. HMB-11.02, Houston, TX 77030 (e-mail: blevin{at}notes.mdacc.tmc.edu).

Worldwide, colorectal cancer is the third most common form of cancer in men and the second in women, with approximately 875 000 new cases diagnosed annually with 570 000 deaths (1). In the United States, colorectal cancer is the fourth most common cancer and the second leading cause of cancer death. Annually, approximately 129 000 new cases of colorectal cancer are diagnosed, with 57 000 associated deaths (2). Early detection through effective screening is one of the strategies to decrease mortality from colorectal cancer.

The evidence to support the effectiveness of population-based screening by means of fecal occult blood testing (FOBT) and flexible sigmoidoscopy continues to mount (3). FOBT screening has been extensively studied in three prospectively randomized controlled trials involving more than 250 000 participants, one in the United States, one in the U.K, and one in Denmark (4-6). The University of Minnesota trial involving nearly 47 000 volunteers (men and women aged 50-80 years) was the first long-term randomized controlled study of FOBT screening to report definitive endpoint results (4). In 1993, after 13 years of screening and follow-up, the study investigators reported a 33% reduction in mortality from colorectal cancer in a group screened annually with Hemoccult® slides, mostly rehydrated, (SmithKline Diagnostics, San Jose, CA). More recently, the English (5) and Danish (6) studies showed statistically significant mortality reductions of 15% and 18%, respectively, from biennial FOBT without rehydration.

The University of Minnesota trial also evaluated biennial screening as reported in this issue of the Journal (7). After 18 years of follow-up, the biennial group had a 21% lower colorectal cancer mortality rate than the control group (rate ratio, 0.79; 95%, CI = 0.62-0.97). Early in the study, the cumulative colorectal cancer mortality was greater in the biennial than in the control group, a trend that was reversed by the 11th year.

The finding of a beneficial effect of biennial screening (7) is of considerable public health importance and confirms the findings of the other two randomized, controlled trials. However, in trying to understand better these results and their implications, it would be of great interest to know the relative incidence of early stage cancer in the annual, biennial and control groups. The reduction in stage IV (8) cancer could be due to earlier detection of cancer or it could be due to a reduction in incidence attributable to adenoma detection and removal, as alluded to by the authors in a recent publication (9).

Fletcher (10) has suggested that in reporting results of screening programs, it is important to calculate not only relative risk reduction but also absolute risk reduction incorporating the number needed to screen. Towler et al. (11) have used this approach to evaluate screening programs in terms of benefit and potential harm. Reduction in colorectal cancer mortality and a possible reduction in incidence through detection and removal of adenomas are very important benefits of screening. Furthermore, individuals who undergo colonoscopy because of a "false-positive" screen and who are found to have no adenomas probably do not need to be screened for a decade. Detection of early stage colorectal cancer also may involve less postsurgical care such as adjuvant therapy. Harmful effects of screening include complications caused by colonoscopy that are infrequent and anxiety and expense caused by false-positive screening tests.

One of the potential limitations to the benefits of colorectal cancer screening as recommended by the U.S. Preventive Services Task Force (12), the American Cancer Society (13), and a consortium of five medical and surgical gastroenterological societies (14) is the low compliance rate outside of study populations. For example, in the 1992 National Health Interview Study, 26% of the population more than 49 years of age reported an FOBT within the prior 3 years and 33% reported ever having had a sigmoidoscopy (15). Even as we strive to develop better screening methods (16,17), greater compliance with existing recommendations would substantially decrease morbidity and mortality from colorectal cancer. The implementation of biennial rather than annual FOBT may also enhance acceptability. In addition, recent legislation authorizing coverage by Medicare of colorectal cancer screening services should provide a substantial incentive to the public and medical care system to enhance compliance. While other strategies, such as chemoprevention (18) or life style changes, may ultimately surpass the effectiveness of periodic screening, for the present, screening with FOBT remains the only proven strategy from randomized prospective trials. For example, the decades-old assumption that a high-fiber diet protects against the development of colorectal cancer has recently been challenged in a large, prospective epidemiologic study (19). As science continues to grapple with issues related to the primary prevention of colorectal cancer using dietary intervention and chemoprevention, and while we await results from clinical trials, the report by Mandel et al. substantiates the important and clear finding that screening of men and women more than 50 years of age for colorectal cancer can save lives.

REFERENCES

1 WHO. World Health Organization. The World Health Report WHO. Geneva (Switzerland); 1977.

2 Landis SH, Murray T, Bolden S, Wingo PA. Cancer statistics, 1999. CA Cancer J Clin 1999;49:8-31.[Abstract/Free Full Text]

3 Young GP. Screening for colorectal cancer: Clinical methods. In: Young GP, Rozen P, Levin B, editors. Prevention and early detection of colorectal cancer. London (England): Saunders; 1996. p. 241-70, 1996.

4 Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, 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;328:1365-71.[Abstract/Free Full Text]

5 Hardcastle JD, Chamberlain JO, Robinson MH, Moss SM, Amar SS, Balfour TW, et al. Randomized controlled trial of a faecal-occult-blood screening for colorectal cancer. Lancet 1996;384:1472-7.

6 Kronborg O, Ferger C, Olsen J, Jorgensen OD, Sondergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348:1467-71.[Medline]

7 Mandel JS, Church TR, Ederer F, Bond JH. Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst 1999;91:434-7.[Abstract/Free Full Text]

8 International Union Against Cancer. TNM classification of malignant tumours. Berlin (Germany): Springer-Verlag; 1987.

9 Ederer F, Church TR, Mandel JS. Fecal occult blood screening in the Minnesota study: role of chance detection of lesions. J Natl Cancer Inst 1997;89:1423-8.[Abstract/Free Full Text]

10 Fletcher SW. Evidenced-based screening: What kind of evidence is needed? [editorial]. ACP Journal Club 128(3) A-12-14, May/June 1998.

11 Towler BP, Irwig L, Glasziou P, Wetter D, Kewenter J. Screening for colorectal cancer using the faecal occult blood test (Hemoccult). Cochrane Review in: The Cochrane Library, Issue 4, 1998, Oxford (U.K.): Update Software.

12 Preventive Services Task Force. Guide to clinical preventive services, 2nd ed. Baltimore (MD): Williams & Wilkins, 1996.

13 Byers T, Levin B, Rothenberger D, Dodd GD, Smith RA. American Cancer Society guidelines for screening and surveillance for early detection of colorectal polyps and cancer: update 1997. American Cancer Society Detection and Treatment Advisory Group on Colorectal Cancer.CA Cancer J Clin 1997;47:154-60.[Abstract/Free Full Text]

14 Winawer SJ, Fletcher RH, Miller L, Godlee F, Stolar MH, Mulrow CD. Colorectal cancer screening: clinical guidelines and rationale [published errata appear in Gastroenterology 1997;112:1060 and 1998;114:625]. Gastroenterology 1997;112:594-642.[Medline]

15 Vernon SW. Participation in colorectal cancer screening: a review. J Natl Cancer Inst 1997;89:1406-22.[Abstract/Free Full Text]

16 Jen J, Johnson C, Levin B. Molecular approaches for colorectal cancer screening. Eur J Gastroenterol Hepatol 1998;10:213-7.[Medline]

17 Fenlon HM, Clarke PD, Ferrucci JT. Virtual colonoscopy: imaging features with colonoscopic correlation. AJR Am J Roentgenol 1998;170:1303-9.[Medline]

18 Lippman SM, Lee JJ, Sabichi AL. Cancer chemoprevention: progress and promise. J Natl Cancer Inst 1998;90:1514-28[Free Full Text]

19 Fuchs CS, Giovannucci EL, Colditz GA, Hunter DJ, Stampfer MJ, Rosner B, et al. Dietary fiber and the risk of colorectal cancer and adenoma in women. N Engl J Med 1999;340:169-76.[Abstract/Free Full Text]


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