2010-07-06 15:33:07 UTC

Colorectal Cancer Screening: Which is the Best Test?

July 6, 2010

Sidney J. Winawer, MD, AGAF, MACG, FASGE

Sidney J. Winawer, MD, AGAF, MACG, FASGE

Paul Sherlock Chair in Medicine, Memorial Sloan-Kettering Cancer Center; Professor of Medicine, Weill Cornell Medical College, New York  


Anyone reading the eye-catching headlines or the full New York Times (NYT) cancer screening articles this past year would most likely conclude that screening has little value. Only by reading carefully and completely, would it be apparent that breast and prostate cancer were being specifically addressed. The reporters state later and briefly that colorectal cancer (CRC) screening is recommended and is effective. Not stated is that CRC screening is unique, having the potential to prevent cancer altogether, unlike breast and prostate cancer screening.1


Is CRC screening effective?

Figure 1: Death Rates from CRC per 100,000 Population

The effectiveness of CRC screening was challenged from the start. Early results of screening programs were glowing, with a predominance of early-stage cancers reported. This can be misleading. Many early-stage cancers may not surface and death may be from another cause (over-diagnosis bias). Cancers may be detected before symptoms appear, identifying the disease longer, but not improving outcome (lead-time bias). Screening may uncover less aggressive cancers more often (length bias). Long-term randomized controlled trials (RCTs) that have a mortality endpoint of the entire cohort eliminate these biases. For CRC screening, three RCTs of quiaiac fecal occult blood test (FOBT) showed significant mortality reductions.1

Figure 2: CRC Incidence Rates per 100,00 Age>50 YearsThe NYT articles cited the increase in annual incidence and lack of a mortality reduction nationally for breast and prostate cancer. The articles did not cite the decrease in annual incidence and mortality of CRC during the same time frame, decreased cancer incidence from removing adenomatous polyps, the predominant neoplastic screening outcome, and the decreased mortality from earlier stage of cancers detected (figures 1 and 2).2


“One-stop shopping”

Colonoscopy provides screening, diagnosis and treatment, and is the most commonly selected option in the U.S. and many other countries. We have learned much about its performance: 5 percent of a mixed gender cohort ages greater than or equal to 50 have advanced adenomas; less than 1 percent have cancer, and complications are rare.3, 4 Removal of all visible adenomatous polyps during colonoscopy results in about a 90 percent CRC incidence and mortality reduction.5 Retrospective studies have suggested a 50 percent to 75 percent mortality reduction in the general population, but the impact appears to be greater for distal as compared to proximal disease either due to a difference in biology or a less effective examination of the right colon.6, 7 Outcome is better when performed by a gastroenterologist. Precise data will be forthcoming in 10 to 15 years from several RCTs in Europe and the U.S.

Although screening colonoscopy has prevention potential, this screening modality results in a large resource expenditure. Polyps of all histological types are found in 30 percent of men and women, requiring polypectomy with its attendant risks. Of the 5 percent of a mixed gender cohort with advanced adenomas, 10 percent may progress to cancer over 10 years: an estimated 200 colonoscopies and 60 polypectomies to prevent one cancer. It is possible that high-definition/advanced imaging endoscopes may obviate the need to remove adenomatous polyps or alternatively, to resect and discard small polyps.


Two-stage approach

It would be desirable to have an effective two-stage screening approach, with the first stage identifying high-risk patients for targeted colonoscopy. Compliers who are q-FOBT positive and have colonoscopy have a 40 percent CRC mortality reduction, but only a 20 percent reduction in incidence, and therefore prevention is largely lost. Fecal immunochemical tests have a higher sensitivity and specificity. It is becoming the preferred FOBT since it can be done in one day and requires no dietary restrictions. The FOBT effect is limited since less than 50 percent of patients adhere to annual testing. Flexible sigmoidoscopy followed by colonoscopy, if positive, significantly reduced the incidence and mortality of distal colorectal cancer over an 11-year period of observation in an RCT in the U.K.8 Stool DNA testing and CT colonography (CTC) are promising and are included as options in the U.S. multi-society guidelines. Issues are: whole stool requirement and intervals (DNA), radiation, extra-colonic findings, flat adenoma miss rate (CTC) and cost-effectiveness (both).3 The future first-stage screening test may be a highly sensitive and specific molecular blood test.


Best test

CRC screening is a package. In addition to high-quality screening, it needs timely diagnosis, timely effective treatment and appropriate surveillance. It is effective. Deaths can be avoided, and many cancers prevented.6 The NYT articles raise the issue of which is the best test. No test is perfect. All have issues. All provide some level of protection. The best test is the one that gets done, and done well.


1. Winawer SJ, Fletcher RH, Miller L, et al. Colorectal Cancer Screening: Clinical Guidelines and Rationale. Gastroenterology 1997;112:594-642.
2. Jemal A, Siegel R, Ward E, et al. Cancer Statistics, 2009. CA Cancer J Clin 2009;59:225-249.
3. Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 2008;134:1570-1595.
4. Regula J, Rupinski M, Kraszewska E, et al. Colonoscopy in Colorectal-Cancer Screening for Detection of Advanced Neoplasia. N Engl J Med 2006;355:1863-1872.
5. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by colonoscopic polypectomy. N Engl J Med 1993;329:1977-1981.
6. Brenner H, Haug U, Arndt V, et al. Low Risk of Colorectal Cancer and Advanced Adenomas More Than 10 Years After Negative Colonoscopy. Gastroenterology 2010;138:870-876.
7. Baxter NN, Goldwasser MA, Paszat LF, et al. Association of Colonoscopy and Death from Colorectal Cancer. Ann Intern Med 2009;150:1-8.
8. Atkin W, Cuzik J, Duffy S, et al. 283 UK Flexible Sigmoidoscopy Screening Trial: Colorectal Cancer Incidence and Mortality Rates at 11 Years After a Single Screening Examination. Gastroenterology 2010;138:S-53.

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