Screening test accuracy

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Systematic review evidence

For persons without a colorectal cancer diagnosis or symptoms that might indicate colorectal cancer, which screening modality (immunochemical faecal occult blood test [iFOBTA 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.], 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 sigmoidoscopyA 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. 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 (iFOBTA 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.) 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 iFOBTA 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. 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 iFOBTA 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.[15][16] or the SEPT9[14] cancer-specific biomarker depending on participant age, and a few studies reported the diagnostic performance for iFOBTA 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.[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 (iFOBTA 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.)

The diagnostic performance for detection of colorectal cancer using iFOBTA 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. 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. ColorectalReferring to the large bowel, comprising the colon and rectum. 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 iFOBTA 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. 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 iFOBTA 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. 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)

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 iFOBTA 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. 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

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

  1. Australian Cancer Network ColorectalReferring to the large bowel, comprising the colon and rectum. 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. 5.05.1 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 Abstract available at http://annals.org/aim/article/743535/screening-colorectal-cancer-u-s-preventive-services-task-force-recommendation.
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  34. 34.034.134.234.334.434.534.6 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 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/26520415.
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Appendices


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