Screening benefit

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Systematic review evidence

In 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, CT colonographyAlso known as virtual colonoscopy, a medical imaging procedure that uses low dose radiation CT scanning to obtain an interior view of the colon (the large bowel) that is otherwise only seen with a more invasive procedure where an endoscope is inserted into the rectum and passed through the entire colon., faecal or blood biomarkers, or any combinations) compared with no screening, reduces colorectal cancer mortality, or the incidence of metastases at diagnosis? (PSC1a)

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 three 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.

At the time of publication of the 2005 Australian Guidelines[1] the only high level evidence of screening benefit was from three randomised controlled trials (RCTs).[7][8][9][10][11][12] All three RCTs used Hemoccult, a guaiac faecal occult blood test (gFOBTA 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.). These trials collectively reported that screening for faecal occult blood reduced overall mortality from colorectal cancer on the basis of intention-to-screen by 15–33% (noting that the trials involved differing numbers of rounds of screening and differing follow-up periods). These findings are further supported by a 2012 update from the Nottingham trial of faecal occult blood testing for colorectal cancer [13] which, after a median of 19.5 years’ follow-up, reported a colorectal cancer-specific mortality reduction of 13%. To date, only one published RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control.[14] has compared 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.) to no screening in a population based setting. In this study, 94,423 individuals were offered once-only 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. screening and follow-up was 8 years.

The update systematic review identified four level II RCTs reported in 5 articles comparing outcomes for an asymptomatic population receiving flexible sigmoidoscopy with no screening (no contact). [15][16][17][18][19] No RCTs conducted in an asymptomatic population were found which compared any other screening methodology to no screening.

A meta-analysis of pooled data from the United Kingdom Flexible Sigmoidoscopy ScreeningPerforming tests to identify disease in people before any symptoms appear. (UKFSS), Norwegian ColorectalReferring to the large bowel, comprising the colon and rectum. Cancer Prevention (NORCCAP), Italian ‘SCreening for COlonREctum’ (SCORE) and US Prostate, Lung, ColorectalReferring to the large bowel, comprising the colon and rectum. and Ovarian (PLCO) trials was also identified.[20] This meta-analysis was at low risk of bias, and reported colorectal cancer-specific mortality, with subgroup analysis for distal and proximal disease.

Overall (all-cause) mortality

None of the screening RCTs,[7][8][9][15][16][14][18] whether based on screening by FOBT or flexible sigmoidoscopy, reported any significant difference in overall (all-cause) mortality.

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ColorectalReferring to the large bowel, comprising the colon and rectum. cancer-specific mortality

As reported in the review supporting the 2005 ColorectalReferring to the large bowel, comprising the colon and rectum. Cancer guidelines,[1] three level II RCTs reported colorectal cancer-specific mortality in gFOBTA 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. screening trials.[7][8][9] These trials, which involved 1–11 rounds of screening, collectively reported that screening for faecal occult blood reduced overall colorectal cancer-specific mortality on the basis of intention-to-screen by 15–33%. The 2012 update from the Nottingham trial[13] reported a colorectal cancer-specific mortality reduction of 13% at approximately 20 years follow-up. A 2003 Chinese RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control.[14] reported a statistically significant 32% reduction in rectal cancer mortality (Poisson test U = 2.5, p < 0.05, log-rank test p = 0.003), but no reduction in colonic (log-rank test, p = 0.222) or overall colorectal cancer-specific mortality. ColonoscopyAn examination of the large bowel using a camera on a flexible tube, which is passed through the anus. was only performed in those participants with a positive 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. when flexible sigmoidoscopy failed to reveal a distal lesion and then only if a second round 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. proved to be positive (0.16%).[14]

In this update review of the flexible sigmoidoscopy trials, the UKFSS,[17] and PLCO[16] trials both reported a statistically significant reduction in colorectal cancer specific mortality in the screened group compared with the control (no screening) group after a single round of sigmoidoscopy screening and screening with follow-up durations from 7–12 years. The relative reduction in colorectal cancer-specific mortality varied from hazard ratio (HR) 0.57[17] to relative risk (RR) 0.74.[16] In the final NORCCAP trial report[18] intention-to-treat analysis showed a significant reduction in colorectal cancer-specific mortality (HR = 0.73, p = 0.02) in the screened group. The NORCCAP trial is unique among these RCTs, as 50% of those screened had 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. in addition to flexible sigmoidoscopy.[18] In sub-analysis according to the screening modality, the overall reduction in colorectal cancer-specific mortality was statistically significant only for those who had both flexible sigmoidoscopy and 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. (HR = 0.62, p = 0.01) and not for flexible sigmoidoscopy alone (HR = 0.84, p = 0.30).

The meta-analysis[20] of pooled data from the UKFSS,[17] NORCCAP,[19] SCORE,[15] and PLCO[16] trials included data from a population of 337,905 participants with an average weighted median follow-up period of 10.8 years. It showed a statistically significant reduction in colorectal cancer-specific mortality in flexible sigmoidoscopy screened group, compared with the non-screened group: 28% relative risk reduction (RR = 0.72; 95% confidence interval (CI) 0.65 to 0.80).

All populations included in this update systematic review[15][16][17][14][18][19][20], were asymptomatic and from Western countries (UK, Sweden, Norway, USA, Italy), except for one RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. conducted in a Chinese population.[14] The early gFOBTA 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. screening trials[10][11][12] included participants from USA, UK, and Denmark.

In three flexible sigmoidoscopy trials,[15][16][17] those involved were volunteers who expressed willingness to accept flexible sigmoidoscopy if randomised to the screening arm. Reported participation rates may therefore over-estimate participation rates achievable in the general population.

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Application of the evidence on screening benefit

To date, the only RCTA study in which people are allocated at random (by chance alone) to receive one of several clinical interventions. One of these interventions is the standard of comparison or control. level evidence comparing screening with an unscreened control group comes from three large gFOBTA 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. trials[7][8][9] first reported in the 1990s, one 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. trial,[14] and the recent flexible sigmoidoscopy trials.[15][16][17][18][19][20]

Currently, many countries around the world, including Australia, New Zealand, Canada, and a number of European countries, have established national population-based colorectal cancer screening programs that utilise either gFOBTA 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. or 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 screening. The use of FOBT is the preferred screening modality in those countries, based on the available evidence and their own screening experience.

An advantage of FOBT is that the test kit can be posted in the mail to the participant, with collection of tiny samples at home and return of these samples by mail. As reported in the 2010 European guidelines for quality assurance in colorectal cancer screening and diagnosis,[2] iFOBTs have the added advantage that they specifically detect human globin, and there is no need to change diet or medication prior to testing. The analysis of many brands 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. is automated and a number of them allow quantitative analysis of haemoglobin. In contrast, flexible sigmoidoscopy is an invasive procedure, requiring a highly trained workforce and special facilities. There are particular concerns about its acceptability and feasibility in the Australian setting as well as its cost-effectiveness.

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

Next section: screening test accuracy

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References

  1. 1.01.11.2 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. 2.02.1 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.
  7. 7.07.17.27.3 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. N Engl J Med 1993 May 13;328(19):1365-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8474513.
  8. 8.08.18.28.3 Hardcastle JD, Chamberlain JO, Robinson MH, Moss SM, Amar SS, Balfour TW, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996 Nov 30;348(9040):1472-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8942775.
  9. 9.09.19.29.3 Kronborg O, Fenger C, Olsen J, Jørgensen OD, Søndergaard O. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996 Nov 30;348(9040):1467-71 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/8942774.
  10. 10.010.1 Mandel JS, Church TR, Ederer F, Bond JH. Colorectal cancer mortality: effectiveness of biennial screening for fecal occult blood. J Natl Cancer Inst 1999 Mar 3;91(5):434-7 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/10070942.
  11. 11.011.1 Jørgensen OD, Kronborg O, Fenger C. A randomised study of screening for colorectal cancer using faecal occult blood testing: results after 13 years and seven biennial screening rounds. Gut 2002 Jan;50(1):29-32 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/11772963.
  12. 12.012.1 Scholefield JH, Moss S, Sufi F, Mangham CM, Hardcastle JD. Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial. Gut 2002 Jun;50(6):840-4 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12010887.
  13. 13.013.1 Scholefield JH, Moss SM, Mangham CM, Whynes DK, Hardcastle JD. Nottingham trial of faecal occult blood testing for colorectal cancer: a 20-year follow-up. Gut 2012 Jul;61(7):1036-40 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22052062.
  14. 14.014.114.214.314.414.514.6 Zheng S, Chen K, Liu X, Ma X, Yu H, Chen K, et al. Cluster randomization trial of sequence mass screening for colorectal cancer. Dis ColonThe main part of the large bowel, which absorbs water and electrolytes from undigested food (solid waste). Its four parts are the ascending colon, transverse colon, descending colon and sigmoid colon. RectumThe final section of the large bowel, ending at the anus. 2003 Jan;46(1):51-8 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/12544522.
  15. 15.015.115.215.315.415.5 Segnan N, Armaroli P, Bonelli L, Risio M, Sciallero S, Zappa M, et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial--SCORE. J Natl Cancer Inst 2011 Sep 7;103(17):1310-22 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/21852264.
  16. 16.016.116.216.316.416.516.616.7 Schoen RE, Pinsky PF, Weissfeld JL, Yokochi LA, Church T, Laiyemo AO, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 2012 Jun 21;366(25):2345-57 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/22612596.
  17. 17.017.117.217.317.417.517.6 Atkin WS, Edwards R, Kralj-Hans I, Wooldrage K, Hart AR, Northover JM, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010 May 8;375(9726):1624-33 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/20430429.
  18. 18.018.118.218.318.418.5 Holme Ø, Løberg M, Kalager M, Bretthauer M, Hernán MA, Aas E, et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA 2014 Aug 13;312(6):606-15 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25117129.
  19. 19.019.119.219.3 Hoff G, Grotmol T, Skovlund E, Bretthauer M, Norwegian ColorectalReferring to the large bowel, comprising the colon and rectum. Cancer Prevention Study Group. Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial. BMJ 2009 May 29;338:b1846 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/19483252.
  20. 20.020.120.220.3 Shroff J, Thosani N, Batra S, Singh H, Guha S. Reduced incidence and mortality from colorectal cancer with flexible-sigmoidoscopy screening: a meta-analysis. World J Gastroenterol 2014 Dec 28;20(48):18466-76 Abstract available at http://www.ncbi.nlm.nih.gov/pubmed/25561818.

Appendices


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