Systematic review evidence[edit source]
In 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, CT colonography, 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.
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)
- the Ontario Ministry of Health and Long-term Care’s Fecal occult blood test for colorectal cancer screening: evidence-based analysis (2009).
- the Ontario Ministry of Health and Long-term Care’s Flexible sigmoidoscopy for colorectal cancer screening: an evidence-based analysis (2009).
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 of its 2008 colorectal cancer screening guidelines. The literature described in the 2016 edition is also covered in this review.
At the time of publication of the 2005 Australian Guidelines the only high level evidence of screening benefit was from three randomised controlled trials (RCTs). All three RCTs used Hemoccult, a guaiac faecal occult blood test (gFOBT). 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  which, after a median of 19.5 years’ follow-up, reported a colorectal cancer-specific mortality reduction of 13%. To date, only one published RCT has compared immunochemical faecal occult blood test (iFOBT) to no screening in a population based setting. In this study, 94,423 individuals were offered once-only iFOBT 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).  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 Screening (UKFSS), Norwegian Colorectal Cancer Prevention (NORCCAP), Italian ‘SCreening for COlonREctum’ (SCORE) and US Prostate, Lung, Colorectal and Ovarian (PLCO) trials was also identified. 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[edit source]
None of the screening RCTs, whether based on screening by FOBT or flexible sigmoidoscopy, reported any significant difference in overall (all-cause) mortality.
Colorectal cancer-specific mortality[edit source]
As reported in the review supporting the 2005 Colorectal Cancer guidelines, three level II RCTs reported colorectal cancer-specific mortality in gFOBT screening trials. 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 reported a colorectal cancer-specific mortality reduction of 13% at approximately 20 years follow-up. A 2003 Chinese RCT 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. Colonoscopy was only performed in those participants with a positive iFOBT when flexible sigmoidoscopy failed to reveal a distal lesion and then only if a second round iFOBT proved to be positive (0.16%).
In this update review of the flexible sigmoidoscopy trials, the UKFSS, and PLCO 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 to relative risk (RR) 0.74. In the final NORCCAP trial report 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 iFOBT in addition to flexible sigmoidoscopy. 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 iFOBT (HR = 0.62, p = 0.01) and not for flexible sigmoidoscopy alone (HR = 0.84, p = 0.30).
The meta-analysis of pooled data from the UKFSS, NORCCAP, SCORE, and PLCO 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, were asymptomatic and from Western countries (UK, Sweden, Norway, USA, Italy), except for one RCT conducted in a Chinese population. The early gFOBT screening trials included participants from USA, UK, and Denmark.
In three flexible sigmoidoscopy trials, 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.
Application of the evidence on screening benefit[edit source]
To date, the only RCT level evidence comparing screening with an unscreened control group comes from three large gFOBT trials first reported in the 1990s, one iFOBT trial, and the recent flexible sigmoidoscopy trials.
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 gFOBT or iFOBT 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, 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 iFOBT 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
- ↑ 1.0 1.1 1.2 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.
- ↑ 2.0 2.1 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.
- ↑ 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.
- ↑ Medical Advisory Secretariat. Flexible sigmoidoscopy for colorectal cancer screening: an evidence-based analysis. Toronto, Ontario: Canada: Ministry of Health and Long-Term Care; 2009.
- ↑ 5.0 5.1 U.S. Preventive Services Task Force. Screening for Colorectal Cancer US Preventive Services Task Force Recommendation Statement. JAMA 2016;315:2564-75.
- ↑ 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.
- ↑ 7.0 7.1 7.2 7.3 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8474513.
- ↑ 8.0 8.1 8.2 8.3 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8942775.
- ↑ 9.0 9.1 9.2 9.3 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/8942774.
- ↑ 10.0 10.1 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/10070942.
- ↑ 11.0 11.1 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/11772963.
- ↑ 12.0 12.1 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12010887.
- ↑ 13.0 13.1 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22052062.
- ↑ 14.0 14.1 14.2 14.3 14.4 14.5 14.6 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 Colon Rectum 2003 Jan;46(1):51-8 Available from: http://www.ncbi.nlm.nih.gov/pubmed/12544522.
- ↑ 15.0 15.1 15.2 15.3 15.4 15.5 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/21852264.
- ↑ 16.0 16.1 16.2 16.3 16.4 16.5 16.6 16.7 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/22612596.
- ↑ 17.0 17.1 17.2 17.3 17.4 17.5 17.6 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/20430429.
- ↑ 18.0 18.1 18.2 18.3 18.4 18.5 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25117129.
- ↑ 19.0 19.1 19.2 19.3 Hoff G, Grotmol T, Skovlund E, Bretthauer M, Norwegian Colorectal Cancer Prevention Study Group. Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial. BMJ 2009 May 29;338:b1846 Available from: http://www.ncbi.nlm.nih.gov/pubmed/19483252.
- ↑ 20.0 20.1 20.2 20.3 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 Available from: http://www.ncbi.nlm.nih.gov/pubmed/25561818.