Colorectal cancer

Screening test accuracy

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Guideline contents > Colorectal cancer screening test accuracy

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Professor James St. John AO; MB,BS; MD; D Med Sc; FRCP; FRACP; AGAF, Dr Hooi Ee MB; BS; PhD; FRACP, Canfell,K, Chetcuti, A, Emery, J, Paul Grogan, Macrae, F, Professor Mark Jenkins PhD BSc, Rachel Mulqueeney MPH; BHSci (OT), Cancer Council Australia Colorectal Cancer Guidelines Working Party. Clinical question:Colorectal cancer screening test accuracy . In: Clinical practice guidelines for the prevention, early detection and management of colorectal cancer. Sydney: Cancer Council Australia. [Version URL: https://wiki.cancer.org.au/australiawiki/index.php?oldid=173041, cited 2023 May 28]. Available from: https://wiki.cancer.org.au/australia/Guidelines:Colorectal_cancer.


Last modified:
7 November 2017 23:30:48

Systematic review evidence[edit source]

For persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer, which screening modality (immunochemical faecal occult blood test [iFOBT], flexible sigmoidoscopy, colonoscopy, faecal or blood biomarkers, or any combination) performs best in detecting colorectal cancer, and does the diagnostic performance change with family history, age, or sex? (PSC1b)

A systematic review was performed to update the 2005 Australian guidelines for the prevention, early detection and management of colorectal cancer.[1]

We identified later relevant evidence-based guidelines which conducted systematic reviews of the literature for the period 2004–2010:

  • the International Agency for Research on Cancer’s European guidelines for quality assurance in colorectal cancer screening and diagnosis (2010)[2]
  • the Ontario Ministry of Health and Long-term Care’s Fecal occult blood test for colorectal cancer screening: evidence-based analysis (2009).[3]
  • the Ontario Ministry of Health and Long-term Care’s Flexible sigmoidoscopy for colorectal cancer screening: an evidence-based analysis (2009).[4]

We chose to adapt these guidelines, updating the systematic literature review up to 31 August 2016. The search strategy, inclusion and exclusion criteria, and quality assessment are described in detail in the Technical report.

While this systematic review was in preparation, the US Preventive Services Task Force published the 2016 update[5] of its 2008 colorectal cancer screening guidelines.[6] The literature described in the 2016 edition[5] is also covered in this review.

Our update systematic review identified 29 diagnosis accuracy studies[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] reporting the performance of colorectal cancer screening modalities, including immunochemical FOBT (iFOBT) and faecal or plasma biomarkers for the detection of colorectal cancer and/or advanced adenoma.

All studies used colonoscopy as the reference standard and all participants underwent colonoscopy. Three studies[8][9][10] (1,333 participants in total) reported the performance of iFOBT at detecting colorectal cancer and/or advanced adenoma in an above average risk population with known family history of colorectal cancer.

The majority of studies (26 in total) used iFOBTs of various brands. Very few studies reported blood/plasma cancer-specific biomarkers, or faecal cancer-specific biomarkers. Only three studies[11][12][34] reported the performance of multi-target faecal DNA tests. One study[13] reported the diagnostic performance of the faecal cancer-specific biomarker MMP-9 protein, and another[14] reported the diagnostic performance of plasma cancer-specific biomarker SEPT9 methylated DNA. Several studies reported the diagnostic performance of iFOBT[15][16] or the SEPT9[14] cancer-specific biomarker depending on participant age, and a few studies reported the diagnostic performance for iFOBT[15][17] or the SEPT9 cancer-specific biomarker[14] by sex. All participants had a colonoscopy as the reference standard.

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Immunochemical faecal occult blood test (iFOBT)[edit source]

The diagnostic performance for detection of colorectal cancer using iFOBT was reported across 20 studies,[7][8][10][12][16][18][19][20][21][22][23][24][25][26][27][28][29][30][34][35] most of which used an Eiken branded test kit. Colorectal cancer prevalence determined by reference colonoscopy was 0.48% in a combined population of 100,093 participants in these 20 studies. All studies consistently reported a sensitivity of greater than 50%, with most studies reporting sensitivities in the 60–85% range. Specificity was consistently high across all 20 studies and ranged from 85% to 100%. The positive predictive value ranged from 1% to 25%, with the majority of studies reporting single-digit values. Negative predictive value was consistently above 99% for most studies.

The diagnostic performance for detection of advanced adenomas using iFOBT was reported in 13 studies. [7][12][15][19][20][26][28][29][30][31][32][34][35] The prevalence of advanced adenomas was 4.5% in a combined population of 60,671 participants included in these 13 studies. Sensitivities reported were lower than for colorectal cancer, the majority of studies reporting 20–40% sensitivity. Specificity was consistently high and most studies reported > 85%. Most studies reported a positive predictive value for adenoma ranging from 20–40%. Negative predictive value was consistently > 90%.

The diagnostic performance for detection of colorectal cancer and/or advanced adenomas was reported in 10 studies.[8][10][16][17][18][22][23][25][27][33] The prevalence of colorectal cancer and/or advanced adenomas was 3.6% in a combined population of 40,272 participants included in these 10 studies. Sensitivities reported ranged from 5% to 75%, but was commonly reported in the range 40–60%. Specificity was > 80% in most studies, and positive predictive value was < 30% in most studies. Negative predictive value was > 90% for all studies.

Only three studies[8][9][10] reported the diagnostic performance of iFOBT for the detection of colorectal cancer and/or advanced adenoma in above-average risk populations with known family history of colorectal cancer. These studies reported inconsistent results. No studies reported the use of biomarker assays in this above average risk population.

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Faecal cancer-specific biomarker (DNA)[edit source]

One study reported the diagnostic performance of two faecal DNA tests[11] for the detection of colorectal cancer. In addition, two studies[12][34] reported different multi-target faecal DNA assays to detect colorectal cancer.

Both multi-target faecal DNA tests outperformed other faecal DNA tests. One study reported sensitivities above 90%,[12] and the other reported sensitivities ranging from 25% to 58%.[34]

Specificities were above 84% for all tests reported.[11]

Two studies reported the diagnostic performance of faecal DNA tests[11][34] at detecting advanced adenomas. Reported sensitivities ranged from 17% to 46% and specificities ranged from 84% to 96%.

One study[12] reported the diagnostic performance of a multi-target faecal DNA in combination with an iFOBT for detection of colorectal cancer and/or advanced adenomas. Sensitivity and specificity were 42.4% and 86.6% respectively.[12]

No studies reported the use of faecal biomarker assays in an above-average risk population.

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Blood cancer-specific biomarkers[edit source]

A single study[14] reported the diagnostic performance of a plasma methylated SEPT9 DNA assay for the detection of colorectal cancer or advanced adenomas. Sensitivities ranged from 48% to 56% and specificity ranged from 89% to 92%, depending on age (< 65 versus ≥ 65 years) or sex analysis for detection of colorectal cancer. Sensitivities ranged from 4.6% to 13% and specificity ranged from 88.6% to 92.6%, depending on age (< 65 versus ≥ 65 years) or sex analysis for detection of advanced adenomas.

No studies specifically reported the diagnostic performance of blood cancer-specific biomarker assays for advance neoplasms (i.e. the combination of cancer and advanced adenomas) or in participants with above-average risk of colorectal cancer.

See the Evidence summary and recommendations section for guidance resulting from this systematic review.

Next section: screening cost effectiveness

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References[edit source]

  1. ↑ Australian Cancer Network Colorectal Cancer Guidelines Revision Committee. Clinical practice guidelines for the prevention, early detection and management of colorectal cancer. The Cancer Council Australia and Australian Cancer Network 2005.
  2. ↑ International Agency for Research on Cancer. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition: International Agency for Research on Cancer; 2010.
  3. ↑ Medical Advisory Secretariat. Fecal Occult Blood Test for Colorectal Cancer Screening: an evidence-based analysis. Toronto, Ontario: Canada: Ministry of Health and Long-Term Care; 2009.
  4. ↑ Medical Advisory Secretariat. Flexible sigmoidoscopy for colorectal cancer screening: an evidence-based analysis. Toronto, Ontario: Canada: Ministry of Health and Long-Term Care; 2009.
  5. ↑ 5.0 5.1 U.S. Preventive Services Task Force. Screening for Colorectal Cancer US Preventive Services Task Force Recommendation Statement. JAMA 2016;315:2564-75.
  6. ↑ U.S. Preventive Services Task Force, Agency for Healthcare Research and Quality. Screening for Colorectal Cancer: U.S. Preventive Services Task Force Recommendation Statement. Annals of Internal Medicine 2008;149:627-37 Available from: http://annals.org/aim/article/743535/screening-colorectal-cancer-u-s-preventive-services-task-force-recommendation.
  7. ↑ 7.0 7.1 7.2 Park DI, Ryu S, Kim YH, Lee SH, Lee CK, Eun CS, et al. Comparison of guaiac-based and quantitative immunochemical fecal occult blood testing in a population at average risk undergoing colorectal cancer screening. Am J Gastroenterol 2010 Sep;105(9):2017-25 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20502450.
  8. ↑ 8.0 8.1 8.2 8.3 8.4 Castro I, Cubiella J, Rivera C, González-Mao C, Vega P, Soto S, et al. Fecal immunochemical test accuracy in familial risk colorectal cancer screening. Int J Cancer 2014 Jan 15;134(2):367-75 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23818169.
  9. ↑ 9.0 9.1 9.2 Gimeno-García AZ, Quintero E, Nicolás-Pérez D, Hernández-Guerra M, Parra-Blanco A, Jiménez-Sosa A. Screening for familial colorectal cancer with a sensitive immunochemical fecal occult blood test: a pilot study. Eur J Gastroenterol Hepatol 2009 Sep;21(9):1062-7 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19307978.
  10. ↑ 10.0 10.1 10.2 10.3 10.4 Ng SC, Ching JY, Chan V, Wong MC, Suen BY, Hirai HW, et al. Diagnostic accuracy of faecal immunochemical test for screening individuals with a family history of colorectal cancer. Aliment Pharmacol Ther 2013 Oct;38(7):835-41 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23957462.
  11. ↑ 11.0 11.1 11.2 11.3 11.4 Ahlquist DA, Sargent DJ, Loprinzi CL, Levin TR, Rex DK, Ahnen DJ, et al. Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann Intern Med 2008 Oct 7;149(7):441-50, W81 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18838724.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 12.7 Imperiale TF, Ransohoff DF, Itzkowitz SH, Levin TR, Lavin P, Lidgard GP, et al. Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med 2014 Apr 3;370(14):1287-97 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24645800.
  13. ↑ 13.0 13.1 Annaházi A, Ábrahám S, Farkas K, Rosztóczy A, Inczefi O, Földesi I, et al. A pilot study on faecal MMP-9: a new noninvasive diagnostic marker of colorectal cancer. Br J Cancer 2016 Mar 29;114(7):787-92 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26908323.
  14. ↑ 14.0 14.1 14.2 14.3 14.4 Church TR, Wandell M, Lofton-Day C, Mongin SJ, Burger M, Payne SR, et al. Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut 2014 Feb;63(2):317-25 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23408352.
  15. ↑ 15.0 15.1 15.2 15.3 Khalid-de Bakker CA, Jonkers DM, Sanduleanu S, de Bruïne AP, Meijer GA, Janssen JB, et al. Test performance of immunologic fecal occult blood testing and sigmoidoscopy compared with primary colonoscopy screening for colorectal advanced adenomas. Cancer Prev Res (Phila) 2011 Oct;4(10):1563-71 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21750209.
  16. ↑ 16.0 16.1 16.2 16.3 Chen Y-Y, Chen T-H, Su M-Y, Ning H-C, Kuo C-J, Lin W-P, et al.. Accuracy of immunochemical fecal occult blood test for detecting colorectal neoplasms in individuals undergoing health check-ups. Advances in Digestive Medicine 2014 Sep;Volume 1, Issue 3, Pages 74–79 Available from: http://www.aidm-online.com/article/S2351-9797(14)00045-0/abstract.
  17. ↑ 17.0 17.1 17.2 Brenner H, Haug U, Hundt S. Sex differences in performance of fecal occult blood testing. Am J Gastroenterol 2010 Nov;105(11):2457-64 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20700114.
  18. ↑ 18.0 18.1 18.2 Brenner H, Tao S. Superior diagnostic performance of faecal immunochemical tests for haemoglobin in a head-to-head comparison with guaiac based faecal occult blood test among 2235 participants of screening colonoscopy. Eur J Cancer 2013 Sep;49(14):3049-54 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23706981.
  19. ↑ 19.0 19.1 19.2 Chiu HM, Lee YC, Tu CH, Chen CC, Tseng PH, Liang JT, et al. Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test. Clin Gastroenterol Hepatol 2013 Jul;11(7):832-8.e1-2 Available from: http://www.ncbi.nlm.nih.gov/pubmed/23376002.
  20. ↑ 20.0 20.1 20.2 de Wijkerslooth TR, Stoop EM, Bossuyt PM, Meijer GA, van Ballegooijen M, van Roon AH, et al. Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia. Am J Gastroenterol 2012 Oct;107(10):1570-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22850431.
  21. ↑ 21.0 21.1 Elsafi SH, Alqahtani NI, Zakary NY, Al Zahrani EM. The sensitivity, specificity, predictive values, and likelihood ratios of fecal occult blood test for the detection of colorectal cancer in hospital settings. Clin Exp Gastroenterol 2015;8:279-84 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26392783.
  22. ↑ 22.0 22.1 22.2 Hernandez V, Cubiella J, Gonzalez-Mao MC, Iglesias F, Rivera C, Iglesias MB, et al. Fecal immunochemical test accuracy in average-risk colorectal cancer screening. World J Gastroenterol 2014 Jan 28;20(4):1038-47 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24574776.
  23. ↑ 23.0 23.1 23.2 Kato J, Morikawa T, Kuriyama M, Yamaji Y, Wada R, Mitsushima T, et al. Combination of sigmoidoscopy and a fecal immunochemical test to detect proximal colon neoplasia. Clin Gastroenterol Hepatol 2009 Dec;7(12):1341-6 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19426835.
  24. ↑ 24.0 24.1 Lee YC, Chiu HM, Chiang TH, Yen AM, Chiu SY, Chen SL, et al. Accuracy of faecal occult blood test and Helicobacter pylori stool antigen test for detection of upper gastrointestinal lesions. BMJ Open 2013 Oct 30;3(10):e003989 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24176798.
  25. ↑ 25.0 25.1 25.2 Lee YH, Hur M, Kim H, Jeon KN, Yun CH, Lee CH, et al. Optimal cut-off concentration for a faecal immunochemical test for haemoglobin by Hemo Techt NS-Plus C15 system for the colorectal cancer screening. Clin Chem Lab Med 2015 Feb;53(3):e69-71 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25153599.
  26. ↑ 26.0 26.1 26.2 Morikawa T, Kato J, Yamaji Y, Wada R, Mitsushima T, Shiratori Y. A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population. Gastroenterology 2005 Aug;129(2):422-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/16083699.
  27. ↑ 27.0 27.1 27.2 Omata F, Shintani A, Isozaki M, Masuda K, Fujita Y, Fukui T. Diagnostic performance of quantitative fecal immunochemical test and multivariate prediction model for colorectal neoplasms in asymptomatic individuals. Eur J Gastroenterol Hepatol 2011 Nov;23(11):1036-41 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21897207.
  28. ↑ 28.0 28.1 28.2 Parra-Blanco A, Gimeno-García AZ, Quintero E, Nicolás D, Moreno SG, Jiménez A, et al. Diagnostic accuracy of immunochemical versus guaiac faecal occult blood tests for colorectal cancer screening. J Gastroenterol 2010 Jul;45(7):703-12 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20157748.
  29. ↑ 29.0 29.1 29.2 Terhaar sive Droste JS, Oort FA, van der Hulst RW, van Heukelem HA, Loffeld RJ, van Turenhout ST, et al. Higher fecal immunochemical test cutoff levels: lower positivity rates but still acceptable detection rates for early-stage colorectal cancers. Cancer Epidemiol Biomarkers Prev 2011 Feb;20(2):272-80 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21135261.
  30. ↑ 30.0 30.1 30.2 Viana Freitas BR, Kibune Nagasako C, Pavan CR, Silva Lorena SL, Guerrazzi F, Saddy Rodrigues Coy C, et al. Immunochemical fecal occult blood test for detection of advanced colonic adenomas and colorectal cancer: comparison with colonoscopy results. Gastroenterol Res Pract 2013;2013:384561 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24319453.
  31. ↑ 31.0 31.1 Graser A, Stieber P, Nagel D, Schäfer C, Horst D, Becker CR, et al. Comparison of CT colonography, colonoscopy, sigmoidoscopy and faecal occult blood tests for the detection of advanced adenoma in an average risk population. Gut 2009 Feb;58(2):241-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/18852257.
  32. ↑ 32.0 32.1 Hundt S, Haug U, Brenner H. Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med 2009 Feb 3;150(3):162-9 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19189905.
  33. ↑ 33.0 33.1 Levy BT, Bay C, Xu Y, Daly JM, Bergus G, Dunkelberg J, et al. Test characteristics of faecal immunochemical tests (FIT) compared with optical colonoscopy. J Med Screen 2014 Sep;21(3):133-43 Available from: http://www.ncbi.nlm.nih.gov/pubmed/24958730.
  34. ↑ 34.0 34.1 34.2 34.3 34.4 34.5 34.6 Redwood DG, Asay ED, Blake ID, Sacco PE, Christensen CM, Sacco FD, et al. Stool DNA Testing for Screening Detection of Colorectal Neoplasia in Alaska Native People. Mayo Clin Proc 2016 Jan;91(1):61-70 Available from: http://www.ncbi.nlm.nih.gov/pubmed/26520415.
  35. ↑ 35.0 35.1 35.2 Nakazako M. YH, Matsushita H., Sato K., Fujita K., Yamanaka Y., Imai Y.. Immunologic Fecal Occult Blood test for Colorectal cancer Screening. Japan med Assoc J 2006 Jun;49:203-7 Available from: http://www.med.or.jp/english/pdf/2006_05+/203_207.pdf.

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Appendices[edit source]

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View Systematic review report PSC1b Systematic review report PSC1b


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Referring to the large bowel, comprising the colon and rectum.

A test that can detect microscopic amounts of blood in stools. Types of FOBT include immunochemical FOBTs (iFOBTs), which directly detect haemoglobin using antibodies specific for the globin moiety of human haemoglobin, and guaiac FOBTs (gFOBTs), which detect peroxidase activity, an indirect method for identification of haemoglobin.

A procedure used by physicians to examine the inner lining of the rectum, particularly the lower portion of the colon (unlike the colonoscopy that examines the entirety of the colon). It consists of a flexible tube that is approximately 60 cm long, a small light and a camera attached at the tip of the tube.

A medical professional who treats acute and chronic illnesses and provides preventive care and health education to a wide range of patients.

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