Colonoscopy Reduces Colorectal Cancer Incidence and Mortality in Patients With Non-Malignant Findings: A Meta-Analysis

Jun Pan, Lei Xin, Yi-Fei Ma, Liang-Hao Hu, Zhao-Shen Li, Jun Pan, Lei Xin, Yi-Fei Ma, Liang-Hao Hu, Zhao-Shen Li

Abstract

Objectives: Observational studies have shown that colonoscopy reduces colorectal cancer (CRC) incidence and mortality in the general population. We aimed to conduct a meta-analysis quantifying the magnitude of protection by colonoscopy, with screening and diagnostic indications, against CRC in patients with non-malignant findings and demonstrating the potentially more marked effect of screening over diagnostic colonoscopy.

Methods: PubMed, EMBASE, and conference abstracts were searched through 30 April 2015. The primary outcomes were overall CRC incidence and mortality. Pooled relative risks (RRs) and 95% confidence intervals (CIs) were calculated using random-effect models.

Results: Eleven observational studies with a total of 1,499,521 individuals were included. Pooled analysis showed that colonoscopy was associated with a 61% RR reduction in CRC incidence (RR: 0.39; 95% CI: 0.26-0.60; I(2)=93.6%) and a 61% reduction in CRC mortality (RR: 0.39; 95% CI: 0.35-0.43; I(2)=12.0%) in patients with non-malignant findings, although there was high heterogeneity for the outcome of CRC incidence. After excluding one outlier study, there was low heterogeneity for the outcome of incidence (I(2)=44.7%). Subgroup analysis showed that the effect of screening colonoscopy was more prominent, corresponding to an 89% reduction in CRC incidence (RR: 0.11; 95% CI: 0.08-0.15), in comparison with settings involving diagnostic colonoscopy (RR: 0.51; 95% CI: 0.43-0.59; P<0.001).

Conclusions: On the basis of this meta-analysis of observational studies, CRC incidence and mortality in patients with non-malignant findings are significantly reduced after colonoscopy. The effect of screening colonoscopy on CRC incidence is more marked than diagnostic colonoscopy.

Figures

Figure 1
Figure 1
Flow diagram of literature search and study selection.
Figure 2
Figure 2
Forest plot of reduction in colorectal cancer incidence after colonoscopy in patients with non-malignant findings.
Figure 3
Figure 3
Forest plot of reduction in colorectal cancer mortality after colonoscopy in patients with non-malignant findings.

References

    1. Ferlay J, Soerjomataram I, Ervik M et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. International Agency for Research on Cancer: Lyon, France. 2013. Available at Accessed on 4 May 2015.
    1. Mandel JS, Church TR, Bond JH et al. The effect of fecal occult-blood screening on the incidence of colorectal cancer. N Engl J Med 2000;343:1603–1607.
    1. Scholefield JH, Moss S, Sufi F et al. Effect of faecal occult blood screening on mortality from colorectal cancer: results from a randomised controlled trial. Gut 2002;50:840–844.
    1. Kronborg O, Jorgensen OD, Fenger C et al. Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds. Scand J Gastroenterol 2004;39:846–851.
    1. Lindholm E, Brevinge H, Haglind E. Survival benefit in a randomized clinical trial of faecal occult blood screening for colorectal cancer. Br J Surg 2008;95:1029–1036.
    1. Shaukat A, Mongin SJ, Geisser MS et al. Long-term mortality after screening for colorectal cancer. N Engl J Med 2013;369:1106–1114.
    1. Hoff G, Grotmol T, Skovlund E et al. Risk of colorectal cancer seven years after flexible sigmoidoscopy screening: randomised controlled trial. BMJ 2009;338:b1846.
    1. Atkin WS, Edwards R, Kralj-Hans I et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010;375:1624–1633.
    1. Segnan N, Armaroli P, Bonelli L et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian randomized controlled trial–SCORE. J Natl Cancer Inst 2011;103:1310–1322.
    1. Schoen RE, Pinsky PF, Weissfeld JL et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 2012;366:2345–2357.
    1. Holme O, Loberg M, Kalager M et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA 2014;312:606–615.
    1. Kaminski MF, Bretthauer M, Zauber AG et al. The NordICC Study: rationale and design of a randomized trial on colonoscopy screening for colorectal cancer. Endoscopy 2012;44:695–702.
    1. Quintero E, Castells A, Bujanda L et al. Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med 2012;366:697–706.
    1. Clinical Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM) 2012. Available at Accessed on 4 May 2015.
    1. Sali L, Grazzini G, Carozzi F et al. Screening for colorectal cancer with FOBT, virtual colonoscopy and optical colonoscopy: study protocol for a randomized controlled trial in the Florence district (SAVE study). Trials 2013;14:74.
    1. Kahi CJ, Imperiale TF, Juliar BE et al. Effect of screening colonoscopy on colorectal cancer incidence and mortality. Clin Gastroenterol Hepatol 2009;7:770–775.
    1. Manser CN, Bachmann LM, Brunner J et al. Colonoscopy screening markedly reduces the occurrence of colon carcinomas and carcinoma-related death: a closed cohort study. Gastrointest Endosc 2012;76:110–117.
    1. Nishihara R, Wu K, Lochhead P et al. Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med 2013;369:1095–1105.
    1. Brenner H, Chang-Claude J, Jansen L et al. Reduced risk of colorectal cancer up to 10 years after screening, surveillance, or diagnostic colonoscopy. Gastroenterology 2014;146:709–717.
    1. Segnan N, Patnick J, von Karsa L. European guidelines for quality assurance in colorectal cancer screening and diagnosis. European Union: Luxembourg. 2010.
    1. Altobelli E, Lattanzi A, Paduano R et al. Colorectal cancer prevention in Europe: burden of disease and status of screening programs. Prev Med 2014;62:132–141.
    1. Sung JJ, Ng SC, Chan FK et al. An updated Asia Pacific Consensus Recommendations on colorectal cancer screening. Gut 2015;64:121–132.
    1. Meester RG, Doubeni CA, Zauber AG et al. Public health impact of achieving 80% colorectal cancer screening rates in the United States by 2018. Cancer, advance online publication, 12 March 2015; doi:10.1002/cncr.29336.
    1. Brenner H, Altenhofen L, Stock C et al. Expected long-term impact of the German screening colonoscopy programme on colorectal cancer prevention: Analyses based on 4,407,971 screening colonoscopies. Eur J Cancer 2015;51:1346–1353.
    1. Baxter NN, Goldwasser MA, Paszat LF et al. Association of colonoscopy and death from colorectal cancer. Ann Intern Med 2009;150:1–8.
    1. Singh H, Nugent Z, Demers AA et al. The reduction in colorectal cancer mortality after colonoscopy varies by site of the cancer. Gastroenterology 2010;139:1128–1137.
    1. Brenner H, Chang-Claude J, Seiler CM et al. Protection from colorectal cancer after colonoscopy: a population-based, case-control study. Ann Intern Med 2011;154:22–30.
    1. Baxter NN, Warren JL, Barrett MJ et al. Association between colonoscopy and colorectal cancer mortality in a US cohort according to site of cancer and colonoscopist specialty. J Clin Oncol 2012;30:2664–2669.
    1. Kahi CJ, Myers LJ, Slaven JE et al. Lower endoscopy reduces colorectal cancer incidence in older individuals. Gastroenterology 2014;146:718–725.
    1. Brenner H, Stock C, Hoffmeister M. Effect of screening sigmoidoscopy and screening colonoscopy on colorectal cancer incidence and mortality: systematic review and meta-analysis of randomised controlled trials and observational studies. BMJ 2014;348:g2467.
    1. Elmunzer BJ, Singal AG, Sussman JB et al. Comparing the effectiveness of competing tests for reducing colorectal cancer mortality: a network meta-analysis. Gastrointest Endosc 2015;81:700–709.
    1. Rex DK. Colonoscopy: a review of its yield for cancers and adenomas by indication. Am J Gastroenterol 1995;90:353–365.
    1. Lieberman DA, Weiss DG, Bond JH et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. Veterans Affairs Cooperative Study Group 380. N Engl J Med 2000;343:162–168.
    1. Lieberman DA, Rex DK, Winawer SJ et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844–857.
    1. Steele RJ, Pox C, Kuipers EJ et al. European guidelines for quality assurance in colorectal cancer screening and diagnosis. First Edition—Management of lesions detected in colorectal cancer screening. Endoscopy 2012;44 Suppl 3:SE140–SE150.
    1. Stroup DF, Berlin JA, Morton SC et al. Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group. JAMA 2000;283:2008–2012.
    1. Wells GA, Shea B, O'Connell D et alThe Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomized studies in meta-analyses Available at Accessed on 4 May 2015.
    1. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev 1987;9:1–30.
    1. DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177–188.
    1. Higgins JP, Thompson SG. Quantifying heterogeneity in a meta-analysis. Stat Med 2002;21:1539–1558.
    1. Higgins JP, Thompson SG, Deeks JJ et al. Measuring inconsistency in meta-analyses. BMJ 2003;327:557–560.
    1. Tobias A. Assessing the influence of a single study in the meta-analysis estimate. Stata Tech Bull 1999;8:15–17.
    1. Altman DG, Bland JM. Interaction revisited: the difference between two estimates. BMJ 2003;326:219.
    1. Begg CB, Mazumdar M. Operating characteristics of a rank correlation test for publication bias. Biometrics 1994;50:1088–1101.
    1. Egger M, Davey Smith G, Schneider M et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997;315:629–634.
    1. Cotterchio M, Manno M, Klar N et al. Colorectal screening is associated with reduced colorectal cancer risk: a case-control study within the population-based Ontario Familial Colorectal Cancer Registry. Cancer Causes Control 2005;16:865–875.
    1. Murakami R, Tsukuma H, Kanamori S et al. Natural history of colorectal polyps and the effect of polypectomy on occurrence of subsequent cancer. Int J Cancer 1990;46:159–164.
    1. Kavanagh AM, Giovannucci EL, Fuchs CS et al. Screening endoscopy and risk of colorectal cancer in United States men. Cancer Causes Control 1998;9:455–462.
    1. Brenner H, Arndt V, Sturmer T et al. Long-lasting reduction of risk of colorectal cancer following screening endoscopy. Br J Cancer 2001;85:972–976.
    1. Rabeneck L, Paszat LF, Saskin R et al. Association between colonoscopy rates and colorectal cancer mortality. Am J Gastroenterol 2010;105:1627–1632.
    1. Steffen A, Weber MF, Roder DM et al. Colorectal cancer screening and subsequent incidence of colorectal cancer: results from the 45 and Up Study. Med J Aust 2014;201:523–527.
    1. Barret M, Boustiere C, Canard JM et al. Factors associated with adenoma detection rate and diagnosis of polyps and colorectal cancer during colonoscopy in France: results of a prospective, nationwide survey. PLoS One 2013;8:e68947.
    1. Doubeni CA, Weinmann S, Adams K et al. Screening colonoscopy and risk for incident late-stage colorectal cancer diagnosis in average-risk adults: a nested case-control study. Ann Intern Med 2013;158:312–320.
    1. Hoffmeister M, Chang-Claude J, Brenner H. Validity of self-reported endoscopies of the large bowel and implications for estimates of colorectal cancer risk. Am J Epidemiol 2007;166:130–136.
    1. Baxter NN, Warren J, Barrett MJ et al. The association between colonoscopy and colorectal cancer mortality in a U.S. cohort according to site of cancer and colonoscopist specialty. Gastroenterology 2011;140:S74–S-75.
    1. Jacob B, Moineddin R, Sutradhar R et al. 658 Effect of colonoscopy on colorectal cancer incidence and mortality: an instrumental variable analysis. Gastrointest Endosc 2012;75:AB155.
    1. Kahi CJ, Myers LJ, Slaven JE et al. 85 endoscopic prevention of colorectal cancer in older individuals. Gastroenterology 2013;144:S19.
    1. Morois S, Cottet V, Racine A et al. Tu1184 colonoscopy, family history of colorectal cancer and colorectal tumor risk: results from a French prospective cohort. Gastroenterology 2012;142:S768–S-769.
    1. Wang YR, Cangemi JR, Loftus EV et al. 766 decreased risk of colorectal cancer after colonoscopy in patients 76-85 years old in the united states: a population-based analysis of the SEER-Medicare Linked Database, 1998-2005. Gastrointest Endosc 2013;77:AB166.
    1. Eldridge RC, Doubeni CA, Fletcher RH et al. Uncontrolled confounding in studies of screening effectiveness: an example of colonoscopy. J Med Screen 2013;20:198–207.
    1. Morois S, Cottet V, Racine A et al. Colonoscopy reduced distal colorectal cancer risk and excess cancer risk associated with family history. Cancer Causes Control 2014;25:1329–1336.
    1. Jacob BJ, Moineddin R, Sutradhar R et al. Effect of colonoscopy on colorectal cancer incidence and mortality: an instrumental variable analysis. Gastrointest Endosc 2012;76:355–364.
    1. Wang YR, Cangemi JR, Loftus EV Jr et al. Risk of colorectal cancer after colonoscopy compared with flexible sigmoidoscopy or no lower endoscopy among older patients in the United States, 1998-2005. Mayo Clin Proc 2013;88:464–470.
    1. Mìller AD, Sonnenberg A. Prevention of colorectal cancer by flexible endoscopy and polypectomy. A case-control study of 32,702 veterans. Ann Intern Med 1995;123:904–910.
    1. Mìller AD, Sonnenberg A. Protection by endoscopy against death from colorectal cancer. A case-control study among veterans. Arch Intern Med 1995;155:1741–1748.
    1. Mulder SA, van Soest EM, Dieleman JP et al. Exposure to colorectal examinations before a colorectal cancer diagnosis: a case-control study. Eur J Gastroenterol Hepatol 2010;22:437–443.
    1. Pan J, Xin L, Li ZS. Modifying the definition of screening exposure to settle existing differences. Gastroenterology 2014;147:717.
    1. Brenner H, Chang-Claude J, Jansen L et al. Reply: To PMID 25075945. Gastroenterology 2014;147:717–718.
    1. Winawer SJ, Zauber AG, Ho MN et al. Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977–1981.
    1. Zauber AG, Winawer SJ, O'Brien MJ et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012;366:687–696.
    1. Singh H, Turner D, Xue L et al. Risk of developing colorectal cancer following a negative colonoscopy examination: evidence for a 10-year interval between colonoscopies. JAMA 2006;295:2366–2373.
    1. le Clercq CM, Bouwens MW, Rondagh EJ et al. Postcolonoscopy colorectal cancers are preventable: a population-based study. Gut 2014;63:957–963.
    1. Keddie N, Hargreaves A. Symptoms of carcinoma of the colon and rectum. Lancet 1968;2:749–750.
    1. Majumdar SR, Fletcher RH, Evans AT. How does colorectal cancer present? Symptoms, duration, and clues to location. Am J Gastroenterol 1999;94:3039–3045.
    1. Soetikno RM, Kaltenbach T, Rouse RV et al. Prevalence of nonpolypoid (flat and depressed) colorectal neoplasms in asymptomatic and symptomatic adults. JAMA 2008;299:1027–1035.
    1. Rex DK, Ahnen DJ, Baron JA et al. Serrated lesions of the colorectum: review and recommendations from an expert panel. Am J Gastroenterol 2012;107:1315–1329.
    1. Singh S, Singh PP, Murad MH et al. Prevalence, risk factors, and outcomes of interval colorectal cancers: a systematic review and meta-analysis. Am J Gastroenterol 2014;109:1375–1389.
    1. Samadder NJ, Curtin K, Tuohy TM et al. Characteristics of missed or interval colorectal cancer and patient survival: a population-based study. Gastroenterology 2014;146:950–960.
    1. Egger M, Schneider M, Davey Smith G. Spurious precision? Meta-analysis of observational studies. BMJ 1998;316:140–144.
    1. Brenner H, Stock C, Hoffmeister M. In the era of widespread endoscopy use, randomized trials may strongly underestimate the effects of colorectal cancer screening. J Clin Epidemiol 2013;66:1144–1150.

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