Background/Aims: The purpose of this review is to clarify the place of new-technology stool tests in screening for colorectal neoplasia. Findings: New technologies have been based on blood and cellular products of neoplasia. Fecal occult blood tests (FOBTs) based on guaiac (i.e. GFOBTs) have been proved to be effective, but their impact on mortality is modest. When GFOBTs are reconfigured to provide improved sensitivity for cancer, their specificity often becomes unacceptable. Fecal immunochemical tests (FITs) targeting the human hemoglobin molecule have been shown to have better sensitivity for neoplasia without an unacceptable deterioration in specificity. The new stool-sampling technologies for FITs also improve population participation rates in screening. Most recently, quantitative FITs have become available; these provide flexibility for the end-user as a desired sensitivity: specificity ratio can be selected that is feasible in the context of available colonoscopic resources. A multi-target fecal DNA test, comprising a test for undegraded DNA and certain common mutations, was found more sensitive for cancer, but not for adenoma, than the early GFOBTs. A more recent version including an epigenetic marker for the vimentin gene has further improved sensitivity for cancer, but performance relative to GFOBT or FIT is not clear. These ‘fecal DNA tests’ have not proved to be more specific for neoplasia than tests that detect blood. Conclusions: FIT should replace GFOBT as the first test in two-step screening of large populations. It is not yet clear that tests targeting nonhemoglobin molecular events provide a clear advantage over FIT.

1.
Young GP, Allison J: Screening for colorectal cancer; in Yamada T, Alpers D, Kaplowitz N, Laine L, Owyang C, Powell D (eds): Textbook of Gastroenterology, ed 5. Philadelphia, Lippincott, Williams and Wilkins, 2007, in press.
2.
Watson JMG, Junger G: Principles and practice of screening for disease. Public Health Pap 1968;34.
3.
Young GP, Macrae FA, St John DJB: Clinical methods of early detection: basis, use and evaluation; in Young GP, Rozen P, Levin B (eds): Prevention and Early Detection of Colorectal Cancer. London, Saunders, 1996, pp 241–270.
4.
Osborn NK, Ahlquist DA: Stool screening for colorectal cancer: molecular approaches. Gastroenterology 2005;128:1–22.
5.
Regueiro CR: AGA Future Trends Committee report: colorectal cancer: a qualitative review of emerging screening and diagnostic technologies. Gastroenterology 2005;129:1083–1103.
[PubMed]
6.
Mandel JS, Bond JH, Church TR, Snover DC, Bradley GM, Schuman LM, Ederer F: Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. NEJM 1993;328:1365–1371.
7.
Kronborg O, Fenger C, Olsen J, Jorgensen OD, Sondergaard O: Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348:1467–1471.
[PubMed]
8.
Hardcastle JD, Chamberlain JO, Robinson MH, Moss SM, Amar SS, Balfour TW, James PD, Mangham CM: Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996;348:1472–1477.
[PubMed]
9.
Mandel JS, Church TR, Bond JH, Ederer F, Geisser MS, Mongin SJ, Snover D, Schuman LM: The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000;343:1603–1607.
[PubMed]
10.
Cole SR, Young GP, Esterman A, Cadd B, Morcom J: A randomized trial of the impact of new fecal hemoglobin test technologies on population participation in screening for colorectal cancer. J Med Screen 2003;10:117–122.
[PubMed]
11.
Allison JE, Tekawa IS, Ransom LJ, Adrain AL: A comparison of fecal occult blood tests for colorectal cancer screening. N Engl J Med 1996;334:155–159.
[PubMed]
12.
Young GP, St John DJB, Winawer SJ, Rozen P: Choice of fecal occult blood tests for colorectal cancer screening: recommendations based on performance characteristics in population studies. Am J Gastroenterol 2002;97:2499–2507.
[PubMed]
13.
Young GP, St John DJB: Faecal occult blood tests: choice, usage and clinical applications. Clin Biochem Rev 1992;13:161–167.
14.
Smith A, Young GP, Cole SR, Bampton P: Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia. Cancer 2006;107:2152–2159.
[PubMed]
15.
Wong BC, Wong WM, Cheung KL, Tong TS, Rozen P, Young GP, Chu KW, Ho J, Law WL, Tung HM, Lai KC, Hu WH, Chan CK, Lam SK: A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population. Aliment Pharmacol Ther 2003;18:941–946.
[PubMed]
16.
Young GP: Molecular approaches to stool screening for colorectal cancer. Curr Colorect Cancer Rep 2006;2:30–35.
17.
Fraser CG, Matthew CM, Mowat NA, Wilson JA, Carey FA, Steele RJ: Immunochemical testing of individuals positive for guaiac faecal occult blood tests in a screening programme for colorectal cancer. Lancet Oncol 2006;7:101–103.
[PubMed]
18.
Levi Z, Rozen P, Hazazi R, Vilkin A, Waked A, Maoz E, Birkenfeld S, Leshno M, Niv Y: A quantitative immunochemical fecal occult blood test for colorectal neoplasia. Ann Intern Med 2007;146:244–255.
[PubMed]
19.
Smith A, Young G, Cole S, Morcom J, Chandler H, La Pointe L: A quantifiable fecal immunochemical test (FIT) for hemoglobin facilitates balancing sensitivity with specificity when screening for colorectal cancer. Gastroenterology 2004;126:S1346.
20.
Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME: Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med 2004;351:2704–2714.
[PubMed]
21.
Woolf SH: A smarter strategy? – reflections on fecal DNA screening for colorectal cancer. N Engl J Med 2004;351:2755–2758.
[PubMed]
22.
Haug U, Hillebrand T, Bendzko P, Low M, Rothenbacher D, Stegmaier C, Brenner H: Mutant-enriched PCR and allele-specific hybridization reaction to detect K-ras mutations in stool DNA. Clin Chem 2007;53:787–790.
[PubMed]
23.
Itzkowitz S, Jandorf L, Brand R, Rabeneck L, Schroy PC 3rd, Sontag S, Johnson D, Skoletsky J, Durkee K, Markowitz S, Shuber A: Improved fecal DNA test for colorectal cancer screening. Clin Gastroenterol Hepatol 2007;5:111–117.
[PubMed]
24.
O’Brien MJ, Yang S, Mack C, Xu H, Huang CS, Mulcahy E, Amorosino M, Farraye FA: Comparison of microsatellite instability, CpG island methylation phenotype, BRAF and KRAS status in serrated polyps and traditional adenomas indicates separate pathways to distinct colorectal carcinoma end points. Am J Surg Pathol 2006;30:1491–1501.
[PubMed]
You do not currently have access to this content.