[Skip to Content]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 54.159.202.12. Please contact the publisher to request reinstatement.
Sign In
Individual Sign In
Create an Account
Institutional Sign In
OpenAthens Shibboleth
[Skip to Content Landing]
Download PDF
Figure 1.
Analytic Framework
Analytic Framework

CTC indicates computed tomographic colonography; FIT, fecal immunochemical test; SIG, flexible sigmoidoscopy; gFOBT, guaiac-based fecal occult blood test; KQ, key question; mSEPT9, circulating methylated septin 9 gene DNA.

Figure 2.
Literature Search Flow Diagram
Literature Search Flow Diagram

KQ indicates key question; MA, meta-analysis; SER, systematic evidence review; SIG, flexible sigmoidoscopy; USPSTF, US Preventive Services Task Force.

aDetails about reasons for exclusion are as follows. Relevance: study aim not relevant. Design: study did not use an included design. Setting: study was not conducted in a country relevant to US practice. Population: study was not conducted in an average-risk population. Outcomes: study did not have relevant outcomes or had incomplete outcomes. Intervention: study used an excluded intervention or screening approach. Quality: study did not meet criteria for fair or good quality. Simulated SIG: study used the distal colon results from a colonoscopy to simulate flexible sigmoidoscopy. SER-MA outdated: study was an existing systematic evidence review with an out-of-date meta-analysis.

Figure 3.
Randomized Clinical Trials of Flexible Sigmoidoscopy Screening and Colorectal Cancer Mortality (Key Question 1)
Randomized Clinical Trials of Flexible Sigmoidoscopy Screening and Colorectal Cancer Mortality (Key Question 1)

Control indicates no colorectal cancer screening; IRR, incidence rate ratio; NORCCAP, Norwegian Colorectal Cancer Prevention; PLCO, Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial; SCORE, Screening for Colon Rectum; UKFSST, UK Flexible Sigmoidoscopy Screening Trial.

Figure 4.
Perforations from Colonoscopy in an Asymptomatic Population (Key Question 3)
Perforations from Colonoscopy in an Asymptomatic Population (Key Question 3)

Note: 1 trial was excluded from the meta-analysis because of a very small number of participants (n = 63).159 There were no episodes of serious bleeding or perforation in the study.

Figure 5.
Major Bleeding From Colonoscopy in an Asymptomatic Population (Key Question 3)
Major Bleeding From Colonoscopy in an Asymptomatic Population (Key Question 3)

Note: 1 trial was excluded from the meta-analysis because of a very small number of participants (n = 63).162 There were no episodes of serious bleeding or perforation in the study.

Figure 6.
Perforations From Flexible Sigmoidoscopy (Key Question 3)
Perforations From Flexible Sigmoidoscopy (Key Question 3)

Note: 1 trial was excluded from the meta-analysis because of a very small number of participants (n = 52).162 There were no episodes of serious bleeding or perforation in the study.

Figure 7.
Major Bleeding From Flexible Sigmoidoscopy (Key Question 3)
Major Bleeding From Flexible Sigmoidoscopy (Key Question 3)

Note: 1 trial was excluded from the meta-analysis because of a very small number of participants (n = 52).162 There were no episodes of serious bleeding or perforation in the study.

Table 1.  
Effectiveness of Screening to Reduce Colorectal Cancer Mortality: Flexible Sigmoidoscopy and Hemoccult II RCTs (Key Question 1)a
Effectiveness of Screening to Reduce Colorectal Cancer Mortality: Flexible Sigmoidoscopy and Hemoccult II RCTs (Key Question 1)a
Table 2.  
Prospective Diagnostic Accuracy Studies of Screening Computed Tomographic Colonography (Key Question 2)
Prospective Diagnostic Accuracy Studies of Screening Computed Tomographic Colonography (Key Question 2)
Table 3.  
Prospective Diagnostic Accuracy Studies of FIT Tests (With or Without Stool DNA Test) Using Colonoscopy Reference Standard (Key Question 2)
Prospective Diagnostic Accuracy Studies of FIT Tests (With or Without Stool DNA Test) Using Colonoscopy Reference Standard (Key Question 2)
Table 4.  
Summary of Evidence by Key Question and Screening Test
Summary of Evidence by Key Question and Screening Test
1.
Cancer Facts and Figures 2013. American Cancer Society. http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2013/. Accessed May 24, 2016.
2.
Centers for Disease Control and Prevention (CDC).  Vital signs: colorectal cancer screening test use: United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(44):881-888.
PubMed
3.
US Preventive Services Task Force.  Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(9):627-637.
PubMedArticle
4.
Levin  B, Lieberman  DA, McFarland  B,  et al; American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee.  Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58(3):130-160.
PubMedArticle
5.
Lin  JS, Piper  MA, Perdue  LA,  et al. Screening for Colorectal Cancer: A Systematic Evidence Review for the US Preventive Services Task Force: Evidence Synthesis No. 135. Rockville, MD: Agency for Healthcare Research and Quality; 2016. AHRQ publication 14-05203-EF-1.
6.
Whitlock  EP, Lin  J, Liles  E,  et al. Screening for Colorectal Cancer: An Updated Systematic Review. Rockville, MD: Agency for Healthcare Research and Quality; 2008.
7.
Pooler  BD, Kim  DH, Pickhardt  PJ.  Potentially important extracolonic findings at screening CT colonography: incidence and outcomes data from a clinical screening program. AJR Am J Roentgenol. 2016;206(2):313-318.
PubMedArticle
8.
Sali  L, Mascalchi  M, Falchini  M,  et al; SAVE Study Investigators.  Reduced and full-preparation CT colonography, fecal immunochemical test, and colonoscopy for population screening of colorectal cancer: a randomized trial. J Natl Cancer Inst. 2015;108(2):108.
PubMed
9.
Redwood  DG, Asay  ED, Blake  ID,  et al.  Stool DNA testing for screening detection of colorectal neoplasia in Alaska Native people. Mayo Clin Proc. 2016;91(1):61-70.
PubMedArticle
10.
Lijmer  JG, Mol  BW, Heisterkamp  S,  et al.  Empirical evidence of design-related bias in studies of diagnostic tests. JAMA. 1999;282(11):1061-1066.
PubMedArticle
11.
Whiting  P, Rutjes  AW, Reitsma  JB, Glas  AS, Bossuyt  PM, Kleijnen  J.  Sources of variation and bias in studies of diagnostic accuracy: a systematic review. Ann Intern Med. 2004;140(3):189-202.
PubMedArticle
12.
Leeflang  MM, Bossuyt  PM, Irwig  L.  Diagnostic test accuracy may vary with prevalence: implications for evidence-based diagnosis. J Clin Epidemiol. 2009;62(1):5-12.
PubMedArticle
13.
Ransohoff  DF, Feinstein  AR.  Problems of spectrum and bias in evaluating the efficacy of diagnostic tests. N Engl J Med. 1978;299(17):926-930.
PubMedArticle
14.
Rutjes  AW, Reitsma  JB, Di Nisio  M, Smidt  N, van Rijn  JC, Bossuyt  PM.  Evidence of bias and variation in diagnostic accuracy studies. CMAJ. 2006;174(4):469-476.
PubMedArticle
15.
Zalis  ME, Barish  MA, Choi  JR,  et al; Working Group on Virtual Colonoscopy.  CT colonography reporting and data system: a consensus proposal. Radiology. 2005;236(1):3-9.
PubMedArticle
16.
Harris  RP, Helfand  M, Woolf  SH,  et al; Methods Work Group, Third US Preventive Services Task Force.  Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3)(suppl):21-35.
PubMedArticle
17.
National Institute for Health and Clinical Excellence. The Guidelines Manual. London, UK: National Institute for Health and Clinical Excellence; 2006.
18.
Shea  BJ, Grimshaw  JM, Wells  GA,  et al.  Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10.
PubMedArticle
19.
Wells  GA, Shea  B, O’Connell  D,  et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis. Ottawa Hospital Research Institute. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed May 25, 2016.
20.
Whiting  P, Rutjes  AW, Reitsma  JB, Bossuyt  PM, Kleijnen  J.  The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25.
PubMedArticle
21.
Whiting  PF, Rutjes  AW, Westwood  ME,  et al; QUADAS-2 Group.  QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529-536.
PubMedArticle
22.
Hardy  RJ, Thompson  SG.  A likelihood approach to meta-analysis with random effects. Stat Med. 1996;15(6):619-629.
PubMedArticle
23.
Thompson  SG, Sharp  SJ.  Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999;18(20):2693-2708.
PubMedArticle
24.
Guolo A, Varin C. Package metaLik. https://cran.r-project.org/web/packages/metaLik/index.html. Accessed May 25, 2016.
25.
Atkin  WS, Edwards  R, Kralj-Hans  I,  et al; UK Flexible Sigmoidoscopy Trial Investigators.  Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010;375(9726):1624-1633.
PubMedArticle
26.
Berry  DP, Clarke  P, Hardcastle  JD, Vellacott  KD.  Randomized trial of the addition of flexible sigmoidoscopy to faecal occult blood testing for colorectal neoplasia population screening. Br J Surg. 1997;84(9):1274-1276.
PubMedArticle
27.
Brevinge  H, Lindholm  E, Buntzen  S, Kewenter  J.  Screening for colorectal neoplasia with faecal occult blood testing compared with flexible sigmoidoscopy directly in a 55-56 years’ old population. Int J Colorectal Dis. 1997;12(5):291-295.
PubMedArticle
28.
Faivre  J, Dancourt  V, Denis  B,  et al.  Comparison between a guaiac and three immunochemical faecal occult blood tests in screening for colorectal cancer. Eur J Cancer. 2012;48(16):2969-2976.
PubMedArticle
29.
Faivre  J, Dancourt  V, Lejeune  C,  et al.  Reduction in colorectal cancer mortality by fecal occult blood screening in a French controlled study. Gastroenterology. 2004;126(7):1674-1680.
PubMedArticle
30.
Guittet  L, Bouvier  V, Mariotte  N,  et al.  Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location. Br J Cancer. 2009;100(8):1230-1235.
PubMedArticle
31.
Hamza  S, Dancourt  V, Lejeune  C, Bidan  JM, Lepage  C, Faivre  J.  Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer. Eur J Cancer. 2013;49(12):2727-2733.
PubMedArticle
32.
Hol  L, van Leerdam  ME, van Ballegooijen  M,  et al.  Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy. Gut. 2010;59(1):62-68.
PubMedArticle
33.
Kronborg  O, Jørgensen  OD, Fenger  C, Rasmussen  M.  Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds. Scand J Gastroenterol. 2004;39(9):846-851.
PubMedArticle
34.
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(8):1029-1036.
PubMedArticle
35.
Malila  N, Palva  T, Malminiemi  O,  et al.  Coverage and performance of colorectal cancer screening with the faecal occult blood test in Finland. J Med Screen. 2011;18(1):18-23.
PubMedArticle
36.
Nishihara  R, Wu  K, Lochhead  P,  et al.  Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med. 2013;369(12):1095-1105.
PubMedArticle
37.
Quintero  E, Castells  A, Bujanda  L,  et al; COLONPREV Study Investigators.  Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med. 2012;366(8):697-706.
PubMedArticle
38.
Rasmussen  M, Kronborg  O, Fenger  C, Jørgensen  OD.  Possible advantages and drawbacks of adding flexible sigmoidoscopy to Hemoccult-II in screening for colorectal cancer: a randomized study. Scand J Gastroenterol. 1999;34(1):73-78.
PubMedArticle
39.
Schoen  RE, Pinsky  PF, Weissfeld  JL,  et al; PLCO Project Team.  Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366(25):2345-2357.
PubMedArticle
40.
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;61(7):1036-1040.
PubMedArticle
41.
Segnan  N, Armaroli  P, Bonelli  L,  et al; SCORE Working Group.  Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial: SCORE. J Natl Cancer Inst. 2011;103(17):1310-1322.
PubMedArticle
42.
Segnan  N, Senore  C, Andreoni  B,  et al; SCORE3 Working Group-Italy.  Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening. Gastroenterology. 2007;132(7):2304-2312.
PubMedArticle
43.
Segnan  N, Senore  C, Andreoni  B,  et al; SCORE2 Working Group-Italy.  Randomized trial of different screening strategies for colorectal cancer: patient response and detection rates. J Natl Cancer Inst. 2005;97(5):347-357.
PubMedArticle
44.
Shaukat  A, Mongin  SJ, Geisser  MS,  et al.  Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106-1114.
PubMedArticle
45.
Stoop  EM, de Haan  MC, de Wijkerslooth  TR,  et al.  Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial. Lancet Oncol. 2012;13(1):55-64.
PubMedArticle
46.
van Roon  AH, Goede  SL, van Ballegooijen  M,  et al.  Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening. Gut. 2013;62(3):409-415.
PubMedArticle
47.
van Rossum  LG, van Rijn  AF, Laheij  RJ,  et al.  Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology. 2008;135(1):82-90.
PubMedArticle
48.
Verne  JECW, Aubrey  R, Love  SB, Talbot  IC, Northover  JM.  Population based randomized study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by faecal occult blood testing. BMJ. 1998;317(7152):182-185.
PubMedArticle
49.
Zubero  MB, Arana-Arri  E, Pijoan  JI,  et al.  Population-based colorectal cancer screening: comparison of two fecal occult blood test. Front Pharmacol. 2014;4:175.
PubMedArticle
50.
Atkin  WS, Cook  CF, Cuzick  J, Edwards  R, Northover  JM, Wardle  J; UK Flexible Sigmoidoscopy Screening Trial Investigators.  Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet. 2002;359(9314):1291-1300.
PubMedArticle
51.
Atkin  WS, Cuzick  J, Northover  JM, Whynes  DK.  Prevention of colorectal cancer by once-only sigmoidoscopy. Lancet. 1993;341(8847):736-740.
PubMedArticle
52.
Bretthauer  M, Gondal  G, Larsen  K,  et al.  Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention). Scand J Gastroenterol. 2002;37(5):568-573.
PubMedArticle
53.
de Wijkerslooth  TR, de Haan  MC, Stoop  EM,  et al.  Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial. BMC Gastroenterol. 2010;10:47.
PubMedArticle
54.
Denters  MJ, Deutekom  M, Bossuyt  PM, Stroobants  AK, Fockens  P, Dekker  E.  Lower risk of advanced neoplasia among patients with a previous negative result from a fecal test for colorectal cancer. Gastroenterology. 2012;142(3):497-504.
PubMedArticle
55.
Denters  MJ, Deutekom  M, Fockens  P, Bossuyt  PM, Dekker  E.  Implementation of population screening for colorectal cancer by repeated fecal occult blood test in the Netherlands. BMC Gastroenterol. 2009;9:28.
PubMedArticle
56.
Faivre  J, Dancourt  V, Manfredi  S,  et al.  Positivity rates and performances of immunochemical faecal occult blood tests at different cut-off levels within a colorectal cancer screening programme. Dig Liver Dis. 2012;44(8):700-704.
PubMedArticle
57.
Guittet  L, Bouvier  V, Guillaume  E,  et al.  Colorectal cancer screening: why immunochemical faecal occult blood test performs as well with either one or two samples. Dig Liver Dis. 2012;44(8):694-699.
PubMedArticle
58.
Guittet  L, Bouvier  V, Mariotte  N,  et al.  Performance of immunochemical faecal occult blood test in colorectal cancer screening in average-risk population according to positivity threshold and number of samples. Int J Cancer. 2009;125(5):1127-1133.
PubMedArticle
59.
Hardcastle  JD, Chamberlain  JO, Robinson  MH,  et al.  Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet. 1996;348(9040):1472-1477.
PubMedArticle
60.
Holme  Ø, Løberg  M, Kalager  M,  et al.  Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA. 2014;312(6):606-615.
PubMedArticle
61.
Kewenter  J, Brevinge  H, Engarås  B, Haglind  E, Ahrén  C.  Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing: results for 68,308 subjects. Scand J Gastroenterol. 1994;29(5):468-473.
PubMedArticle
62.
Malila  N, Oivanen  T, Malminiemi  O, Hakama  M.  Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design. BMJ. 2008;337:a2261.
PubMedArticle
63.
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(22):1603-1607.
PubMedArticle
64.
Mandel  JS, Bond  JH, Church  TR,  et al.  Reducing mortality from colorectal cancer by screening for fecal occult blood: Minnesota Colon Cancer Control Study. N Engl J Med. 1993;328(19):1365-1371.
PubMedArticle
65.
Parra-Blanco  A, Nicolas-Perez  D, Gimeno-Garcia  A,  et al.  The timing of bowel preparation before colonoscopy determines the quality of cleansing, and is a significant factor contributing to the detection of flat lesions: a randomized study. World J Gastroenterol. 2006;12(38):6161-6166.
PubMedArticle
66.
Segnan  N, Senore  C, Andreoni  B,  et al; SCORE Working Group-Italy.  Baseline findings of the Italian multicenter randomized controlled trial of “once-only sigmoidoscopy”: SCORE. J Natl Cancer Inst. 2002;94(23):1763-1772.
PubMedArticle
67.
Thomas  W, White  CM, Mah  J, Geisser  MS, Church  TR, Mandel  JS.  Longitudinal compliance with annual screening for fecal occult blood: Minnesota Colon Cancer Control Study. Am J Epidemiol. 1995;142(2):176-182.
PubMed
68.
Atkin  WS, Cook  CF, Cuzick  J, Edwards  R, Northover  JM, Wardle  J; UK Flexible Sigmoidoscopy Screening Trial Investigators.  Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet. 2002;359(9314):1291-1300.
PubMedArticle
69.
van Roon  AH, Wilschut  JA, Hol  L,  et al.  Diagnostic yield improves with collection of 2 samples in fecal immunochemical test screening without affecting attendance. Clin Gastroenterol Hepatol. 2011;9(4):333-339.
PubMedArticle
70.
van Dam  L, de Wijkerslooth  TR, de Haan  MC,  et al.  Time requirements and health effects of participation in colorectal cancer screening with colonoscopy or computed tomography colonography in a randomized controlled trial. Endoscopy. 2013;45(3):182-188.
PubMedArticle
71.
Weissfeld  JL, Schoen  RE, Pinsky  PF,  et al; PLCO Project Team.  Flexible sigmoidoscopy in the PLCO cancer screening trial: results from the baseline screening examination of a randomized trial. J Natl Cancer Inst. 2005;97(13):989-997.
PubMedArticle
72.
Allison  JE, Sakoda  LC, Levin  TR,  et al.  Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst. 2007;99(19):1462-1470.
PubMedArticle
73.
Allison  JE, Tekawa  IS, Ransom  LJ, Adrain  AL.  A comparison of fecal occult-blood tests for colorectal-cancer screening. N Engl J Med. 1996;334(3):155-159.
PubMedArticle
74.
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;49(14):3049-3054.
PubMedArticle
75.
Castiglione  G, Visioli  CB, Ciatto  S,  et al.  Sensitivity of latex agglutination faecal occult blood test in the Florence District population-based colorectal cancer screening programme. Br J Cancer. 2007;96(11):1750-1754.
PubMedArticle
76.
Chen  LS, Yen  AM, Chiu  SY, Liao  CS, Chen  HH.  Baseline faecal occult blood concentration as a predictor of incident colorectal neoplasia: longitudinal follow-up of a Taiwanese population-based colorectal cancer screening cohort. Lancet Oncol. 2011;12(6):551-558.
PubMedArticle
77.
Cheng  TI, Wong  JM, Hong  CF,  et al.  Colorectal cancer screening in asymptomatic adults: comparison of colonoscopy, sigmoidoscopy and fecal occult blood tests. J Formos Med Assoc. 2002;101(10):685-690.
PubMed
78.
Chiu  HM, Lee  YC, Tu  CH,  et al.  Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test. Clin Gastroenterol Hepatol. 2013;11(7):832-8.e1,2.
PubMedArticle
79.
Church  TR, Wandell  M, Lofton-Day  C,  et al; PRESEPT Clinical Study Steering Committee, Investigators and Study Team.  Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut. 2014;63(2):317-325.
PubMedArticle
80.
de Wijkerslooth  TR, Stoop  EM, Bossuyt  PM,  et al.  Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia. Am J Gastroenterol. 2012;107(10):1570-1578.
PubMedArticle
81.
Fletcher  JG, Silva  AC, Fidler  JL,  et al.  Noncathartic CT colonography: image quality assessment and performance and in a screening cohort. AJR Am J Roentgenol. 2013;201(4):787-794.
PubMedArticle
82.
Graser  A, Stieber  P, Nagel  D,  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;58(2):241-248.
PubMedArticle
83.
Imperiale  TF, Ransohoff  DF, Itzkowitz  SH,  et al.  Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-1297.
PubMedArticle
84.
Itoh  M, Takahashi  K, Nishida  H, Sakagami  K, Okubo  T.  Estimation of the optimal cut off point in a new immunological faecal occult blood test in a corporate colorectal cancer screening programme. J Med Screen. 1996;3(2):66-71.
PubMed
85.
Johnson  CD, Chen  MH, Toledano  AY,  et al.  Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med. 2008;359(12):1207-1217.
PubMedArticle
86.
Johnson  CD, Fletcher  JG, MacCarty  RL,  et al.  Effect of slice thickness and primary 2D versus 3D virtual dissection on colorectal lesion detection at CT colonography in 452 asymptomatic adults. AJR Am J Roentgenol. 2007;189(3):672-680.
PubMedArticle
87.
Kim  YS, Kim  N, Kim  SH,  et al.  The efficacy of intravenous contrast-enhanced 16-raw multidetector CT colonography for detecting patients with colorectal polyps in an asymptomatic population in Korea. J Clin Gastroenterol. 2008;42(7):791-798.
PubMedArticle
88.
Launoy  GD, Bertrand  HJ, Berchi  C,  et al.  Evaluation of an immunochemical fecal occult blood test with automated reading in screening for colorectal cancer in a general average-risk population. Int J Cancer. 2005;115(3):493-496.
PubMedArticle
89.
Lefere  P, Silva  C, Gryspeerdt  S,  et al.  Teleradiology based CT colonography to screen a population group of a remote island; at average risk for colorectal cancer. Eur J Radiol. 2013;82(6):e262-e267.
PubMedArticle
90.
Levi  Z, Birkenfeld  S, Vilkin  A,  et al.  A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate: a prospective, controlled, feasibility study. Int J Cancer. 2011;128(10):2415-2424.
PubMedArticle
91.
Levy  BT, Bay  C, Xu  Y,  et al.  Test characteristics of faecal immunochemical tests (FIT) compared with optical colonoscopy. J Med Screen. 2014;21(3):133-143.
PubMedArticle
92.
Lin  JS, Webber  EM, Beil  TL, Goddard  KA, Whitlock  EP. Fecal DNA Testing in Screening for Colorectal Cancer in Average-Risk Adults. Rockville, MD: Agency for Healthcare Research and Quality; 2012. AHRQ publication 12-EHC022-EF.
93.
Macari  M, Bini  EJ, Jacobs  SL,  et al.  Colorectal polyps and cancers in asymptomatic average-risk patients: evaluation with CT colonography. Radiology. 2004;230(3):629-636.
PubMedArticle
94.
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;129(2):422-428.
PubMedArticle
95.
Nakama  H, Yamamoto  M, Kamijo  N,  et al.  Colonoscopic evaluation of immunochemical fecal occult blood test for detection of colorectal neoplasia. Hepatogastroenterology. 1999;46(25):228-231.
PubMed
96.
Nakama  H, Kamijo  N, Abdul Fattah  AS, Zhang  B.  Validity of immunochemical faecal occult blood screening for colorectal cancer: a follow up study. J Med Screen. 1996;3(2):63-65.
PubMed
97.
Ng  SC, Ching  JY, Chan  V,  et al.  Diagnostic accuracy of faecal immunochemical test for screening individuals with a family history of colorectal cancer. Aliment Pharmacol Ther. 2013;38(7):835-841.
PubMedArticle
98.
Park  DI, Ryu  S, Kim  YH,  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;105(9):2017-2025.
PubMedArticle
99.
Pickhardt  PJ, Choi  JR, Hwang  I,  et al.  Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med. 2003;349(23):2191-2200.
PubMedArticle
100.
Sohn  DK, Jeong  SY, Choi  HS,  et al.  Single immunochemical fecal occult blood test for detection of colorectal neoplasia. Cancer Res Treat. 2005;37(1):20-23.
PubMedArticle
101.
Zalis  ME, Blake  MA, Cai  W,  et al.  Diagnostic accuracy of laxative-free computed tomographic colonography for detection of adenomatous polyps in asymptomatic adults: a prospective evaluation. Ann Intern Med. 2012;156(10):692-702.
PubMedArticle
102.
Chiang  TH, Chuang  SL, Chen  SL,  et al.  Difference in performance of fecal immunochemical tests with the same hemoglobin cutoff concentration in a nationwide colorectal cancer screening program. Gastroenterology. 2014;147(6):1317-1326.
PubMedArticle
103.
Hernandez  V, Cubiella  J, Gonzalez-Mao  MC,  et al; COLONPREV Study Investigators.  Fecal immunochemical test accuracy in average-risk colorectal cancer screening. World J Gastroenterol. 2014;20(4):1038-1047.
PubMedArticle
104.
Lee  YH, Hur  M, Kim  H,  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;53(3):e69-e71.
PubMedArticle
105.
Cologuard summary of safety and effectiveness data (SSED). US Food and Drug Administration. http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130017b.pdf. Accessed May 25, 2016.
106.
Ahlquist  DA, Sargent  DJ, Loprinzi  CL,  et al.  Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann Intern Med. 2008;149(7):441-450,W81.
PubMedArticle
107.
Brenner  H, Haug  U, Hundt  S.  Inter-test agreement and quantitative cross-validation of immunochromatographical fecal occult blood tests. Int J Cancer. 2010;127(7):1643-1649.
PubMedArticle
108.
Brenner  H, Haug  U, Hundt  S.  Sex differences in performance of fecal occult blood testing. Am J Gastroenterol. 2010;105(11):2457-2464.
PubMedArticle
109.
Grazzini  G, Castiglione  G, Ciabattoni  C,  et al.  Colorectal cancer screening programme by faecal occult blood test in Tuscany: first round results. Eur J Cancer Prev. 2004;13(1):19-26.
PubMedArticle
110.
Haug  U, Kuntz  KM, Knudsen  AB, Hundt  S, Brenner  H.  Sensitivity of immunochemical faecal occult blood testing for detecting left- vs right-sided colorectal neoplasia. Br J Cancer. 2011;104(11):1779-1785.
PubMedArticle
111.
Haug  U, Hillebrand  T, Bendzko  P,  et al.  Mutant-enriched PCR and allele-specific hybridization reaction to detect K-ras mutations in stool DNA: high prevalence in a large sample of older adults. Clin Chem. 2007;53(4):787-790.
PubMedArticle
112.
Hundt  S, Haug  U, Brenner  H.  Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med. 2009;150(3):162-169.
PubMedArticle
113.
Imperiale  TF, Ransohoff  DF, Itzkowitz  SH, Turnbull  BA, Ross  ME; Colorectal Cancer Study Group.  Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 2004;351(26):2704-2714.
PubMedArticle
114.
Johnson  CD, Herman  BA, Chen  MH,  et al.  The National CT Colonography Trial: assessment of accuracy in participants 65 years of age and older. Radiology. 2012;263(2):401-408.
PubMedArticle
115.
Morikawa  T, Kato  J, Yamaji  Y,  et al.  Sensitivity of immunochemical fecal occult blood test to small colorectal adenomas. Am J Gastroenterol. 2007;102(10):2259-2264.
PubMedArticle
116.
Adeyemo  A, Bannazadeh  M, Riggs  T, Shellnut  J, Barkel  D, Wasvary  H.  Does sedation type affect colonoscopy perforation rates? Dis Colon Rectum. 2014;57(1):110-114.
PubMedArticle
117.
Adler  A, Wegscheider  K, Lieberman  D,  et al.  Factors determining the quality of screening colonoscopy: a prospective study on adenoma detection rates, from 12,134 examinations (Berlin colonoscopy project 3, BECOP-3). Gut. 2013;62(2):236-241.
PubMedArticle
118.
An  S, Lee  KH, Kim  YH,  et al.  Screening CT colonography in an asymptomatic average-risk Asian population: a 2-year experience in a single institution. AJR Am J Roentgenol. 2008;191(3):W100-W106.
PubMedArticle
119.
Arora  G, Mannalithara  A, Singh  G, Gerson  LB, Triadafilopoulos  G.  Risk of perforation from a colonoscopy in adults: a large population-based study. Gastrointest Endosc. 2009;69(3 pt 2):654-664.
PubMedArticle
120.
Bair  D, Pham  J, Seaton  MB, Arya  N, Pryce  M, Seaton  TL.  The quality of screening colonoscopies in an office-based endoscopy clinic. Can J Gastroenterol. 2009;23(1):41-47.
PubMedArticle
121.
Berhane  C, Denning  D.  Incidental finding of colorectal cancer in screening colonoscopy and its cost effectiveness. Am Surg. 2009;75(8):699-703.
PubMed
122.
Bielawska  B, Day  AG, Lieberman  DA, Hookey  LC.  Risk factors for early colonoscopic perforation include non-gastroenterologist endoscopists: a multivariable analysis. Clin Gastroenterol Hepatol. 2014;12(1):85-92.
PubMedArticle
123.
Blotière  PO, Weill  A, Ricordeau  P, Alla  F, Allemand  H.  Perforations and haemorrhages after colonoscopy in 2010: a study based on comprehensive French health insurance data (SNIIRAM). Clin Res Hepatol Gastroenterol. 2014;38(1):112-117.
PubMedArticle
124.
Bokemeyer  B, Bock  H, Hüppe  D,  et al.  Screening colonoscopy for colorectal cancer prevention: results from a German online registry on 269000 cases. Eur J Gastroenterol Hepatol. 2009;21(6):650-655.
PubMedArticle
125.
Cash  BD, Riddle  MS, Bhattacharya  I,  et al.  CT colonography of a Medicare-aged population: outcomes observed in an analysis of more than 1400 patients. AJR Am J Roentgenol. 2012;199(1):W27-W34.
PubMedArticle
126.
Castro  G, Azrak  MF, Seeff  LC, Royalty  J.  Outpatient colonoscopy complications in the CDC’s Colorectal Cancer Screening Demonstration Program: a prospective analysis. Cancer. 2013;119(suppl 15):2849-2854.
PubMedArticle
127.
Chin  M, Mendelson  R, Edwards  J, Foster  N, Forbes  G.  Computed tomographic colonography: prevalence, nature, and clinical significance of extracolonic findings in a community screening program. Am J Gastroenterol. 2005;100(12):2771-2776.
PubMedArticle
128.
Chukmaitov  A, Bradley  CJ, Dahman  B, Siangphoe  U, Warren  JL, Klabunde  CN.  Association of polypectomy techniques, endoscopist volume, and facility type with colonoscopy complications. Gastrointest Endosc. 2013;77(3):436-446.
PubMedArticle
129.
Cooper  GS, Kou  TD, Rex  DK.  Complications following colonoscopy with anesthesia assistance: a population-based analysis. JAMA Intern Med. 2013;173(7):551-556.
PubMedArticle
130.
Cotterill  M, Gasparelli  R, Kirby  E.  Colorectal cancer detection in a rural community: development of a colonoscopy screening program. Can Fam Physician. 2005;51:1224-1228.
PubMed
131.
Crispin  A, Birkner  B, Munte  A, Nusko  G, Mansmann  U.  Process quality and incidence of acute complications in a series of more than 230,000 outpatient colonoscopies. Endoscopy. 2009;41(12):1018-1025.
PubMedArticle
132.
Dancourt  V, Lejeune  C, Lepage  C, Gailliard  MC, Meny  B, Faivre  J.  Immunochemical faecal occult blood tests are superior to guaiac-based tests for the detection of colorectal neoplasms. Eur J Cancer. 2008;44(15):2254-2258.
PubMedArticle
133.
Dominitz  JA, Baldwin  LM, Green  P, Kreuter  WI, Ko  CW.  Regional variation in anesthesia assistance during outpatient colonoscopy is not associated with differences in polyp detection or complication rates. Gastroenterology. 2013;144(2):298-306.
PubMedArticle
134.
Durbin  JM, Stroup  SP, Altamar  HO, L’esperance  JO, Lacey  DR, Auge  BK.  Genitourinary abnormalities in an asymptomatic screening population: findings on virtual colonoscopy. Clin Nephrol. 2012;77(3):204-210.
PubMedArticle
135.
Edwards  JT, Mendelson  RM, Fritschi  L,  et al.  Colorectal neoplasia screening with CT colonography in average-risk asymptomatic subjects: community-based study. Radiology. 2004;230(2):459-464.
PubMedArticle
136.
Ferlitsch  M, Reinhart  K, Pramhas  S,  et al.  Sex-specific prevalence of adenomas, advanced adenomas, and colorectal cancer in individuals undergoing screening colonoscopy. JAMA. 2011;306(12):1352-1358.
PubMedArticle
137.
Flicker  MS, Tsoukas  AT, Hazra  A, Dachman  AH.  Economic impact of extracolonic findings at computed tomographic colonography. J Comput Assist Tomogr. 2008;32(4):497-503.
PubMedArticle
138.
Ginnerup Pedersen  B, Rosenkilde  M, Christiansen  TE, Laurberg  S.  Extracolonic findings at computed tomography colonography are a challenge. Gut. 2003;52(12):1744-1747.
PubMedArticle
139.
Gluecker  TM, Johnson  CD, Wilson  LA,  et al.  Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population. Gastroenterology. 2003;124(4):911-916.
PubMedArticle
140.
Hamdani  U, Naeem  R, Haider  F,  et al.  Risk factors for colonoscopic perforation: a population-based study of 80118 cases. World J Gastroenterol. 2013;19(23):3596-3601.
PubMedArticle
141.
Hara  AK, Johnson  CD, MacCarty  RL, Welch  TJ.  Incidental extracolonic findings at CT colonography. Radiology. 2000;215(2):353-357.
PubMedArticle
142.
Ho  JM, Gruneir  A, Fischer  HD,  et al.  Serious events in older Ontario residents receiving bowel preparations for outpatient colonoscopy with various comorbidity profiles: a descriptive, population-based study. Can J Gastroenterol. 2012;26(7):436-440.
PubMedArticle
143.
Hoff  G, Thiis-Evensen  E, Grotmol  T, Sauar  J, Vatn  MH, Moen  IE.  Do undesirable effects of screening affect all-cause mortality in flexible sigmoidoscopy programmes? experience from the Telemark Polyp Study 1983-1996. Eur J Cancer Prev. 2001;10(2):131-137.
PubMedArticle
144.
Hsieh  TK, Hung  L, Kang  FC, Lan  KM, Poon  PW, So  EC.  Anesthesia does not increase the rate of bowel perforation during colonoscopy: a retrospective study. Acta Anaesthesiol Taiwan. 2009;47(4):162-166.
PubMedArticle
145.
Iafrate  F, Iussich  G, Correale  L,  et al.  Adverse events of computed tomography colonography: an Italian National Survey. Dig Liver Dis. 2013;45(8):645-650.
PubMedArticle
146.
Jain  A, Falzarano  J, Jain  A, Decker  R, Okubo  G, Fujiwara  D.  Outcome of 5,000 flexible sigmoidoscopies done by nurse endoscopists for colorectal screening in asymptomatic patients. Hawaii Med J. 2002;61(6):118-120.
PubMed
147.
Kamath  AS, Iqbal  CW, Sarr  MG,  et al.  Colonoscopic splenic injuries: incidence and management. J Gastrointest Surg. 2009;13(12):2136-2140.
PubMedArticle
148.
Kang  HY, Kang  HW, Kim  SG,  et al.  Incidence and management of colonoscopic perforations in Korea. Digestion. 2008;78(4):218-223.
PubMedArticle
149.
Kao  KT, Jain  A, Sheinbaum  A.  Ischemic colitis following routine screening colonoscopy: a case report. Endoscopy. 2009;41(suppl 2):E100.
PubMedArticle
150.
Kim  DH, Pickhardt  PJ, Taylor  AJ,  et al.  CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med. 2007;357(14):1403-1412.
PubMedArticle
151.
Kim  JS, Kim  BW, Kim  JI,  et al.  Endoscopic clip closure versus surgery for the treatment of iatrogenic colon perforations developed during diagnostic colonoscopy: a review of 115,285 patients. Surg Endosc. 2013;27(2):501-504.
PubMedArticle
152.
Kim  YS, Kim  N, Kim  SY,  et al.  Extracolonic findings in an asymptomatic screening population undergoing intravenous contrast-enhanced computed tomography colonography. J Gastroenterol Hepatol. 2008;23(7 pt 2):e49-e57.
PubMedArticle
153.
Ko  CW, Riffle  S, Shapiro  JA,  et al.  Incidence of minor complications and time lost from normal activities after screening or surveillance colonoscopy. Gastrointest Endosc. 2007;65(4):648-656.
PubMedArticle
154.
Korman  LY, Overholt  BF, Box  T, Winker  CK.  Perforation during colonoscopy in endoscopic ambulatory surgical centers. Gastrointest Endosc. 2003;58(4):554-557.
PubMedArticle
155.
Layton  JB, Klemmer  PJ, Christiansen  CF,  et al.  Sodium phosphate does not increase risk for acute kidney injury after routine colonoscopy, compared with polyethylene glycol. Clin Gastroenterol Hepatol. 2014;12(9):1514-1521.
PubMedArticle
156.
Levin  TR, Zhao  W, Conell  C,  et al.  Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med. 2006;145(12):880-886.
PubMedArticle
157.
Levin  TR, Conell  C, Shapiro  JA, Chazan  SG, Nadel  MR, Selby  JV.  Complications of screening flexible sigmoidoscopy. Gastroenterology. 2002;123(6):1786-1792.
PubMedArticle
158.
Loffeld  RJ, Engel  A, Dekkers  PE.  Incidence and causes of colonoscopic perforations: a single-center case series. Endoscopy. 2011;43(3):240-242.
PubMedArticle
159.
Lorenzo-Zúñiga  V, Moreno de Vega  V, Doménech  E, Mañosa  M, Planas  R, Boix  J.  Endoscopist experience as a risk factor for colonoscopic complications. Colorectal Dis. 2010;12(10 online):e273-e277.
PubMedArticle
160.
Macari  M, Nevsky  G, Bonavita  J, Kim  DC, Megibow  AJ, Babb  JS.  CT colonography in senior versus nonsenior patients: extracolonic findings, recommendations for additional imaging, and polyp prevalence. Radiology. 2011;259(3):767-774.
PubMedArticle
161.
Mansmann  U, Crispin  A, Henschel  V,  et al.  Epidemiology and quality control of 245 000 outpatient colonoscopies. Dtsch Arztebl Int. 2008;105(24):434-440.
PubMed
162.
Multicentre Australian Colorectal-neoplasia Screening (MACS) Group.  A comparison of colorectal neoplasia screening tests: a multicentre community-based study of the impact of consumer choice. Med J Aust. 2006;184(11):546-550.
PubMed
163.
Nelson  DB, McQuaid  KR, Bond  JH, Lieberman  DA, Weiss  DG, Johnston  TK.  Procedural success and complications of large-scale screening colonoscopy. Gastrointest Endosc. 2002;55(3):307-314.
PubMedArticle
164.
O’Connor  SD, Pickhardt  PJ, Kim  DH, Oliva  MR, Silverman  SG.  Incidental finding of renal masses at unenhanced CT: prevalence and analysis of features for guiding management. AJR Am J Roentgenol. 2011;197(1):139-145.
PubMedArticle
165.
Parente  F, Boemo  C, Ardizzoia  A,  et al.  Outcomes and cost evaluation of the first two rounds of a colorectal cancer screening program based on immunochemical fecal occult blood test in northern Italy. Endoscopy. 2013;45(1):27-34.
PubMed
166.
Pickhardt  PJ, Boyce  CJ, Kim  DH, Hinshaw  LJ, Taylor  AJ, Winter  TC.  Should small sliding hiatal hernias be reported at CT colonography? AJR Am J Roentgenol. 2011;196(4):W400-W404.
PubMedArticle
167.
Pickhardt  PJ, Kim  DH, Meiners  RJ,  et al.  Colorectal and extracolonic cancers detected at screening CT colonography in 10,286 asymptomatic adults. Radiology. 2010;255(1):83-88.
PubMedArticle
168.
Pickhardt  PJ, Kim  DH, Taylor  AJ, Gopal  DV, Weber  SM, Heise  CP.  Extracolonic tumors of the gastrointestinal tract detected incidentally at screening CT colonography. Dis Colon Rectum. 2007;50(1):56-63.
PubMedArticle
169.
Pickhardt  PJ.  Incidence of colonic perforation at CT colonography: review of existing data and implications for screening of asymptomatic adults. Radiology. 2006;239(2):313-316.
PubMedArticle
170.
Pox  CP, Altenhofen  L, Brenner  H, Theilmeier  A, Von Stillfried  D, Schmiegel  W.  Efficacy of a nationwide screening colonoscopy program for colorectal cancer. Gastroenterology. 2012;142(7):1460-1467.
PubMedArticle
171.
Quallick  MR, Brown  WR.  Rectal perforation during colonoscopic retroflexion: a large, prospective experience in an academic center. Gastrointest Endosc. 2009;69(4):960-963.
PubMedArticle
172.
Rabeneck  L, Paszat  LF, Hilsden  RJ,  et al.  Bleeding and perforation after outpatient colonoscopy and their risk factors in usual clinical practice. Gastroenterology. 2008;135(6):1899-1906.
PubMedArticle
173.
Rathgaber  SW, Wick  TM.  Colonoscopy completion and complication rates in a community gastroenterology practice. Gastrointest Endosc. 2006;64(4):556-562.
PubMedArticle
174.
Rutter  CM, Johnson  E, Miglioretti  DL, Mandelson  MT, Inadomi  J, Buist  DS.  Adverse events after screening and follow-up colonoscopy. Cancer Causes Control. 2012;23(2):289-296.
PubMedArticle
175.
Sagawa  T, Kakizaki  S, Iizuka  H,  et al.  Analysis of colonoscopic perforations at a local clinic and a tertiary hospital. World J Gastroenterol. 2012;18(35):4898-4904.
PubMedArticle
176.
Senore  C, Ederle  A, Fantin  A,  et al.  Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting. J Med Screen. 2011;18(3):128-134.
PubMedArticle
177.
Sieg  A, Hachmoeller-Eisenbach  U, Eisenbach  T.  Prospective evaluation of complications in outpatient GI endoscopy: a survey among German gastroenterologists. Gastrointest Endosc. 2001;53(6):620-627.
PubMedArticle
178.
Singh  H, Penfold  RB, DeCoster  C,  et al.  Colonoscopy and its complications across a Canadian regional health authority. Gastrointest Endosc. 2009;69(3 pt 2):665-671.
PubMedArticle
179.
Sosna  J, Blachar  A, Amitai  M,  et al.  Colonic perforation at CT colonography: assessment of risk in a multicenter large cohort. Radiology. 2006;239(2):457-463.
PubMedArticle
180.
Stock  C, Ihle  P, Sieg  A, Schubert  I, Hoffmeister  M, Brenner  H.  Adverse events requiring hospitalization within 30 days after outpatient screening and nonscreening colonoscopies. Gastrointest Endosc. 2013;77(3):419-429.
PubMedArticle
181.
Strul  H, Kariv  R, Leshno  M,  et al.  The prevalence rate and anatomic location of colorectal adenoma and cancer detected by colonoscopy in average-risk individuals aged 40-80 years. Am J Gastroenterol. 2006;101(2):255-262.
PubMedArticle
182.
Suissa  A, Bentur  OS, Lachter  J,  et al.  Outcome and complications of colonoscopy: a prospective multicenter study in northern Israel. Diagn Ther Endosc. 2012;2012:612542.
PubMedArticle
183.
Tam  MS, Abbas  MA.  Perforation following colorectal endoscopy: what happens beyond the endoscopy suite? Perm J. 2013;17(2):17-21.
PubMedArticle
184.
Veerappan  GR, Ally  MR, Choi  JH, Pak  JS, Maydonovitch  C, Wong  RK.  Extracolonic findings on CT colonography increases yield of colorectal cancer screening. AJR Am J Roentgenol. 2010;195(3):677-686.
PubMedArticle
185.
Viiala  CH, Olynyk  JK.  Outcomes after 10 years of a community-based flexible sigmoidoscopy screening program for colorectal carcinoma. Med J Aust. 2007;187(5):274-277.
PubMed
186.
Wallace  MB, Kemp  JA, Meyer  F,  et al.  Screening for colorectal cancer with flexible sigmoidoscopy by nonphysician endoscopists. Am J Med. 1999;107(3):214-218.
PubMedArticle
187.
Warren  JL, Klabunde  CN, Mariotto  AB,  et al.  Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med. 2009;150(12):849-857,W152.
PubMedArticle
188.
Xirasagar  S, Hurley  TG, Sros  L, Hebert  JR.  Quality and safety of screening colonoscopies performed by primary care physicians with standby specialist support. Med Care. 2010;48(8):703-709.
PubMedArticle
189.
Zafar  HM, Harhay  MO, Yang  J, Armstron  K.  Adverse events following computed tomographic colonography compared to optical colonoscopy in the elderly. Prev Med Rep. 2014;1:3-8.
PubMedArticle
190.
Ko  CW, Riffle  S, Michaels  L,  et al.  Serious complications within 30 days of screening and surveillance colonoscopy are uncommon. Clin Gastroenterol Hepatol. 2010;8(2):166-173.
PubMedArticle
191.
Atkin  WS, Hart  A, Edwards  R,  et al.  Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening. Gut. 1998;42(4):560-565.
PubMedArticle
192.
Gondal  G, Grotmol  T, Hofstad  B, Bretthauer  M, Eide  TJ, Hoff  G.  The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years. Scand J Gastroenterol. 2003;38(6):635-642.
PubMedArticle
193.
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;338:b1846.
PubMedArticle
194.
Hoff  G, Sauar  J, Vatn  MH,  et al.  Polypectomy of adenomas in the prevention of colorectal cancer: 10 years’ follow-up of the Telemark Polyp Study I: a prospective, controlled population study. Scand J Gastroenterol. 1996;31(10):1006-1010.
PubMedArticle
195.
Kim  DH, Pickhardt  PJ, Hanson  ME, Hinshaw  JL.  CT colonography: performance and program outcome measures in an older screening population. Radiology. 2010;254(2):493-500.
PubMedArticle
196.
Miles  A, Wardle  J, McCaffery  K, Williamson  S, Atkin  W.  The effects of colorectal cancer screening on health attitudes and practices. Cancer Epidemiol Biomarkers Prev. 2003;12(7):651-655.
PubMed
197.
Pickhardt  PJ, Kim  DH, Robbins  JB.  Flat (nonpolypoid) colorectal lesions identified at CT colonography in a US screening population. Acad Radiol. 2010;17(6):784-790.
PubMedArticle
198.
Pickhardt  PJ, Hanson  ME, Vanness  DJ,  et al.  Unsuspected extracolonic findings at screening CT colonography: clinical and economic impact. Radiology. 2008;249(1):151-159.
PubMedArticle
199.
Regula  J, Polkowski  M.  CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med. 2008;358(1):88-89.
PubMedArticle
200.
Thiis-Evensen  E, Hoff  GS, Sauar  J, Langmark  F, Majak  BM, Vatn  MH.  Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer: Telemark Polyp Study I. Scand J Gastroenterol. 1999;34(4):414-420.
PubMedArticle
201.
Lord  SJ, Irwig  L, Simes  RJ.  When is measuring sensitivity and specificity sufficient to evaluate a diagnostic test, and when do we need randomized trials? Ann Intern Med. 2006;144(11):850-855.
PubMedArticle
203.
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(7):695-702.
PubMedArticle
204.
Castells  A, Quintero  E.  Programmatic screening for colorectal cancer: the COLONPREV study. Dig Dis Sci. 2015;60(3):672-680.
PubMedArticle
205.
Álvarez  C, Andreu  M, Castells  A,  et al; ColonPrev study investigators.  Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals. Gastrointest Endosc. 2013;78(2):333-341.
PubMedArticle
206.
Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01239082. Accessed May 25, 2016.
207.
Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, Board on Radiation Effects Research, Division on Earth and Life Studies, National Research Council of the National Academies. Health Risks From Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC: National Academies Press; 2006.
208.
Cardis  E, Vrijheid  M, Blettner  M,  et al.  Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. BMJ. 2005;331(7508):77.
PubMedArticle
209.
Brenner  DJ, Hall  EJ.  Computed tomography: an increasing source of radiation exposure. N Engl J Med. 2007;357(22):2277-2284.
PubMedArticle
210.
Knudsen  AB, Zauber  AG, Rutter  CM,  et al.  Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA. doi:10.1001/jama.2016.6828.
US Preventive Services Task Force
Evidence Report
June 21, 2016

Screening for Colorectal CancerUpdated Evidence Report and Systematic Review for the US Preventive Services Task Force

Author Affiliations
  • 1Kaiser Permanente Research Affiliates Evidence-based Practice Center, Center for Health Research, Kaiser Permanente, Portland, Oregon
  • 2Group Health Research Institute, Seattle, Washington
  • 3Currently with RAND Corporation, Santa Monica, California
JAMA. 2016;315(23):2576-2594. doi:10.1001/jama.2016.3332
Abstract

Importance  Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in the United States.

Objective  To systematically review the effectiveness, diagnostic accuracy, and harms of screening for CRC.

Data Sources  Searches of MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials for relevant studies published from January 1, 2008, through December 31, 2014, with surveillance through February 23, 2016.

Study Selection  English-language studies conducted in asymptomatic populations at general risk of CRC.

Data Extraction and Synthesis  Two reviewers independently appraised the articles and extracted relevant study data from fair- or good-quality studies. Random-effects meta-analyses were conducted.

Main Outcomes and Measures  Colorectal cancer incidence and mortality, test accuracy in detecting CRC or adenomas, and serious adverse events.

Results  Four pragmatic randomized clinical trials (RCTs) evaluating 1-time or 2-time flexible sigmoidoscopy (n = 458 002) were associated with decreased CRC-specific mortality compared with no screening (incidence rate ratio, 0.73; 95% CI, 0.66-0.82). Five RCTs with multiple rounds of biennial screening with guaiac-based fecal occult blood testing (n = 419 966) showed reduced CRC-specific mortality (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Seven studies of computed tomographic colonography (CTC) with bowel preparation demonstrated per-person sensitivity and specificity to detect adenomas 6 mm and larger comparable with colonoscopy (sensitivity from 73% [95% CI, 58%-84%] to 98% [95% CI, 91%-100%]; specificity from 89% [95% CI, 84%-93%] to 91% [95% CI, 88%-93%]); variability and imprecision may be due to differences in study designs or CTC protocols. Sensitivity of colonoscopy to detect adenomas 6 mm or larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%). On the basis of a single stool specimen, the most commonly evaluated families of fecal immunochemical tests (FITs) demonstrated good sensitivity (range, 73%-88%) and specificity (range, 90%-96%). One study (n = 9989) found that FIT plus stool DNA test had better sensitivity in detecting CRC than FIT alone (92%) but lower specificity (84%). Serious adverse events from colonoscopy in asymptomatic persons included perforations (4/10 000 procedures, 95% CI, 2-5 in 10 000) and major bleeds (8/10 000 procedures, 95% CI, 5-14 in 10 000). Computed tomographic colonography may have harms resulting from low-dose ionizing radiation exposure or identification of extracolonic findings.

Conclusions and Relevance  Colonoscopy, flexible sigmoidoscopy, CTC, and stool tests have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed.

Introduction

Although colorectal cancer (CRC) incidence has been declining over the past 20 years in the United States, it still causes significant morbidity and mortality.1Quiz Ref ID Despite increases in screening rates over the past 30 years, in 2012 an estimated 28% of eligible US adults had never been screened for CRC.2 A variety of tests are available for screening, including stool-based tests (eg, guaiac-based fecal occult blood testing [gFOBT], immunochemical-based fecal occult blood testing [FIT], stool DNA [sDNA] testing), endoscopy (eg, flexible sigmoidoscopy [SIG], colonoscopy), and imaging (eg, double-contrast barium enema, computed tomographic colonography [CTC]).

Quiz Ref IDCurrently, most US guideline organizations, including the US Preventive Services Task Force (USPSTF), recommend that options for CRC screening include colonoscopy every 10 years, an annual high-sensitivity gFOBT or FIT, and SIG every 5 years with high-sensitivity gFOBT or FIT.3,4 In 2008, the USPSTF recommended CRC screening using fecal occult blood testing, sigmoidoscopy, or colonoscopy beginning at age 50 years and continuing until age 75 years (A recommendation); selectively offering screening in adults aged 76 to 85 years (C recommendation); and against screening for colorectal cancer in adults older than 85 years (D recommendation). At that time, the USPSTF had insufficient evidence to assess the benefits and harms of CTC and sDNA testing as screening modalities. A systematic review was conducted to update relevant evidence since 2008 and to help inform a separate modeling exercise, which together were used by the USPSTF in its process of updating the 2008 CRC screening recommendations.

Methods
Scope of Review

This review addressed 3 key questions (KQs) as shown in Figure 1. Additional methodological details regarding search strategies, detailed study inclusion criteria, quality assessment, excluded studies, and description of data analyses are publicly available in the full evidence report at http://www.uspreventiveservicestaskforce.org/Page/Document/final-evidence-review/colorectal-cancer-screening2.5

Data Sources and Searches

MEDLINE, PubMed, and the Cochrane Central Register of Controlled Trials were searched to locate primary studies informing the key questions (eMethods in the Supplement) that were published from the end of the previous review6 (January 1, 2008) through December 31, 2014. The database searches were supplemented with expert suggestions and by reviewing reference lists from all other relevant systematic reviews, including the 2008 USPSTF evidence report. The search also included selected gray literature sources, including ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform, for ongoing trials. Since December 2014, we continued to conduct ongoing surveillance through article alerts and targeted searches of high-impact journals to identify major studies published in the interim that may affect the conclusions or understanding of the evidence and therefore the related USPSTF recommendation. The last surveillance was conducted on February 23, 2016. Although several potentially relevant new studies were identified,79 none of these studies would substantively change the review’s interpretation of findings or conclusions.

Study Selection

Two investigators independently reviewed 8492 titles and abstracts and 696 articles against the specified inclusion criteria (Figure 2). Discrepancies were resolved through consensus and consultation with a third investigator. Inclusion criteria were fair- and good-quality English-language studies of asymptomatic screening populations of individuals who were 40 years or older, either at average risk for CRC or not selected for inclusion based on CRC risk factors. Studies were included that evaluated the following screening tests: colonoscopy, SIG, CTC, gFOBT, FIT, FIT plus sDNA, or a blood test for methylated SEPT9 DNA (mSEPT9).

For KQ1, randomized clinical trials (RCTs) or otherwise controlled trials of CRC screening vs no screening, as well as trials comparing screening tests, that included outcomes of cancer incidence, CRC-specific mortality, or all-cause mortality were reviewed for inclusion. For tests without trial-level evidence (ie, colonoscopy, FIT), well-conducted prospective cohort or population-based nested case-control studies were examined.

For KQ2, diagnostic accuracy studies that used colonoscopy as a reference standard were included. Studies whose design was subject to a high risk of bias were generally excluded, including studies that did not apply colonoscopy to at least a random subset of screen-negative persons (verification bias)10 and studies without an adequate representation of a full spectrum of patients (spectrum bias), such as case-control studies.1014 Selected well-conducted FIT diagnostic accuracy studies that used robust registry follow-up for screen-negative participants were included.

For KQ3, all trials and observational studies that reported serious adverse events requiring unexpected or unwanted medical attention or resulting in death were included. These events included, but were not limited to, perforation, major bleeding, severe abdominal symptoms, and cardiovascular events. Studies designed to assess for extracolonic findings (ie, incidental findings on CTC) and the resultant diagnostic yield and harms of workup were also included. Studies reporting extracolonic findings generally used the CT Colonography Reporting and Data System (C-RADS). Under C-RADS, extracolonic findings are categorized as E0 (limited examination), E1 (normal examination or normal variant), E2 (clinically unimportant finding in which no workup is required), E3 (likely unimportant or incompletely characterized in which workup may be required), or E4 (potentially important finding requiring follow-up).15

Data Extraction and Quality Assessment

Two reviewers each critically appraised all articles that met inclusion criteria using the USPSTF design-specific quality criteria16 supplemented by the National Institute for Health and Clinical Excellence methodology checklists,17 A Measurement Tool to Assess Systematic Reviews (AMSTAR) for systematic reviews,18 Newcastle Ottawa Scales for cohort and case-control studies,19 and Quality Assessment of Diagnostic Accuracy (QUADAS) and QUADAS-2 for studies of diagnostic accuracy (eTable 1 in the Supplement).20,21 Poor-quality studies and those with a single fatal flaw or multiple important limitations that could invalidate results were excluded from this review. Disagreements about critical appraisal were resolved by consensus and, if needed, consultation with a third independent reviewer. One reviewer extracted key data from included studies; a second reviewer checked the data for accuracy.

Data Synthesis and Analysis

For each KQ, the number and design of included studies, overall results, consistency or precision of results, reporting bias, study quality, limitations of the body of evidence, and applicability of findings were summarized. The results were synthesized by KQ, type of screening test, and study design. Studies from the 2008 review that met the updated inclusion criteria were incorporated. The analyses for test performance focused primarily on per-person (ie, by individual patient rather than by lesion) test sensitivity and specificity to detect adenomas (by size, where reported, <6 mm, ≥6 mm, ≥10 mm), advanced adenomas (as defined by the study), and CRC. The studies used several kinds of FITs, which were grouped as qualitative (fixed cutoff) or quantitative (adjustable cutoff), as well as into families (tests produced by the same manufacturer, using the same components and method, or compatible with different automated analyzers). Tests were compared using similar cutoff values expressed in μg hemoglobin (Hb)/g feces.

Because of the limited number of studies and the clinical heterogeneity of studies, the analyses were largely descriptive. Random-effects meta-analyses were conducted using the profile likelihood method22 to estimate the effect of SIG based on the pooled incidence rate ratio (events/person-year) for CRC incidence and mortality across the 4 major SIG trials. Random-effects models were also conducted using the restricted maximum likelihood estimation method to estimate rates of serious adverse events for colonoscopy and SIG. The presence and magnitude of statistical heterogeneity were assessed among pooled studies using the I2 statistic. All tests were 2-sided with a P value less than .05 indicating statistical significance. Meta-analyses were performed using R version 3.0.2 (R Project for Statistical Computing).23,24

Results
Effectiveness of Screening

Key Question 1. What is the effectiveness of screening programs based on the prespecified screening tests (alone or in combination) in reducing incidence of and mortality from colorectal cancer?

Twenty-five unique fair- or good-quality studies2549 (published in 47 articles2571) were found that assessed the effectiveness or comparative effectiveness of screening tests on CRC incidence and mortality. These studies included 1 cohort study of screening colonoscopy,36 4 RCTs of SIG (in 7 articles),25,39,41,50,60,66,71 and 6 trials (in 11 articles) of Hemoccult II gFOBT.29,3335,40,44,59,6264,67 In addition, 15 comparative effectiveness studies (in 22 articles) were found that were primarily designed to assess the relative uptake and CRC yield between different screening modalities.2628,3032,37,38,42,43,4549,5458,65,69 Due to limitations in study designs, the observational colonoscopy study and comparative effectiveness studies are not discussed further in this article. Summarized below are the results for CRC-specific mortality, as results for CRC incidence were consistent with CRC mortality findings.

Flexible Sigmoidoscopy

Four large, fair-quality, pragmatic RCTs (n = 458 002) evaluated the effectiveness of 1 or 2 rounds of SIG in average-risk adults aged 50 to 74 years (Table 1).25,39,41,50,60,66,71 Adherence to SIG in these trials ranged from 58% to 84%, and rates of diagnostic colonoscopy ranged from 5% to 33% due to differences in referral criteria. Based on pooled intention-to-treat analyses, SIG was associated with lower CRC-specific mortality compared with no screening at 11 to 12 years of follow-up (incidence rate ratio, 0.73; 95% CI, 0.66-0.82; I2 = 0%) (Figure 3); however, the association with mortality benefit was limited to distal CRC (incidence rate ratio, 0.63; 95% CI, 0.49-0.84; I2 = 44%) (eFigure 1 in the Supplement). In 1 trial, conducted in Norway, half of the participants randomized to SIG also received a single FIT test; the SIG-plus-FIT group had lower CRC mortality than the SIG-only group did (hazard ratio, 0.62; 95% CI, 0.42-0.90).60

gFOBT

Five older, large, pragmatic RCTs (n = 419 966) with 11 to 30 years of follow-up evaluated the effectiveness of annual or biennial screening programs with Hemoccult II (Table 1).29,33,34,40,44,59,63,64,67 Based on intention-to-treat analyses, compared with no screening, biennial screening with Hemoccult II resulted in a reduction in CRC-specific mortality after 2 to 9 rounds of screening (relative risk [RR], 0.91; 95% CI, 0.84-0.98, at 19.5 years to RR, 0.78; 95% CI, 0.65-0.93, at 30 years). Based on 1 trial, conducted in the United States, annual screening with Hemoccult II after 11 rounds of screening resulted in greater reductions (RR, 0.68; 95% CI, 0.56-0.82) than biennial screening at 30 years did (RR, 0.78; 95% CI, 0.65-0.93).44

Diagnostic Accuracy of Screening

Key Question 2. What are the test performance characteristics of the prespecified screening tests (alone or in combination) for detecting colorectal cancer, advanced adenomas, or adenomatous polyps based on size?

Thirty-three unique diagnostic accuracy studies72104 (published in 44 articles72115) were found that evaluated the 1-time test performance of a screening test compared with an adequate reference standard, including 9 studies of screening CTC (in 10 articles),81,82,8587,89,93,99,101,114 3 studies of gFOBT Hemoccult Sensa,72,73,90 20 studies of various FITs7278,80,8284,88,90,91,9498,100,102104 (1 of which evaluated a FIT plus sDNA test83), and 1 study of a blood test to detect circulating mSEPT9.79 The study of mSEPT9 (not approved by the US Food and Drug Administration [FDA] for screening) and studies evaluating Hemoccult Sensa and FITs that only applied the colonoscopy reference standard to positive stool tests are not discussed further in this article.

Direct Visualization Tests

Nine fair- or good-quality studies (n = 6497) evaluated the diagnostic accuracy of multidetector CTC in average-risk screening populations (Table 2).81,82,8587,89,93,99,101,114 The 2 largest and best-quality studies were multicenter trials conducted in the United States evaluating CTC with bowel preparation and fecal tagging.85,99 Overall, the studies were not powered to estimate test performance to detect CRC. Based on 7 studies of CTC with bowel preparation (n = 5328), the per-person sensitivity to detect adenomas 10 mm and larger ranged from 67% (95% CI, 45%-84%) to 94% (95% CI, 84%-98%), and specificity ranged from 98% (95% CI, 96%-99%) to 96% (95% CI, 95%-97%). The per-person sensitivity to detect adenomas 6 mm and larger ranged from 73% (95% CI, 58%-84%) to 98% (95% CI, 91%-100%), and specificity ranged from 89% (95% CI, 84%-93%) to 91% (95% CI, 88%-93%). Two studies (N = 1169) evaluated CTC without bowel preparation.81,101 Although the data were limited, the sensitivity of CTC without bowel preparation to detect adenomas 6 mm and larger appeared to be lower than the sensitivity of CTC protocols including bowel preparation.

Four (n = 4821) of the 9 CTC studies allowed for the estimation of sensitivity of colonoscopy generalizable to community practice.85,86,99,101 Compared with CTC or colonoscopy plus CTC (eg, segmental unblinding), the sensitivity for colonoscopy to detect adenomas 10 mm and larger ranged from 89% (95% CI, 78%-96%) to 98% (95% CI, 74%-100%) and for adenomas 6 mm and larger ranged from 75% (95% CI, 63%-84%) to 93% (95% CI, 88%-96%) (see full report5). Therefore, CTC with bowel preparation had sensitivity to detect adenomas 6 mm and larger comparable with colonoscopy, albeit with wider variability in estimated performance. It is unclear whether the observed variation in CTC performance was due to differences in study design, populations, bowel preparation, CTC technologies, or differences in reader experience or reading protocols.

Stool Tests

Fourteen fair- or good-quality studies (n = 59 425) that used colonoscopy reference standard in all participants reported sensitivity and specificity for 19 different types of qualitative or quantitative FITs, including 1 FIT plus sDNA test (Table 3).74,77,78,80,82,83,91,94,95,97,98,100,103,104,107,108,115 Overall, the sensitivity for CRC and advanced adenomas varied widely, including a discontinued test with very low sensitivity.100 Given the heterogeneity among FITs and their test performance, focus was placed on the performance characteristics of currently available tests evaluated in more than 1 study. Two families of FDA-cleared tests, OC-Light (qualitative, No. of studies = 3, n = 25 924) and OC FIT-CHEK (eg, OC-Sensor Diana, OC-Micro, OC-Auto) (quantitative, No. of studies = 5, n = 12 794), had relatively high sensitivity and specificity. With a single stool specimen, the lowest sensitivity demonstrated for CRC was 73% (95% CI, 48%-90%) and specificity was 96% (95% CI, 95%-96%). Similarly, the highest sensitivity with paired specificity for CRC was 88% (95% CI, 55%-99%) and 91% (95% CI, 89%-92%), respectively. In the largest studies, sensitivity ranged from 74% (95% CI, 62%-83%) for quantitative test categories (n = 9989) to 79% (95% CI, 61%-90%) for qualitative test categories (n = 18 296). In a small study (n = 770) that tested 3 stool specimens, sensitivity was 92% (95% CI, 69%-99%), but specificity was 87% (95% CI, 85%-89%). OC-Light or OC FIT-CHEK test sensitivity and specificity for advanced adenomas ranged from 22% (95% CI, 17%-28%) to 40% (95% CI, 30%-51%), and specificity ranged from 97% (95% CI, 97%-98%) to 91% (95% CI, 91%-92%). Although higher sensitivities to detect advanced adenomas were obtained for certain other FITs or by using 3 stool specimens, the corresponding specificities were lower.

Cologuard (Exact Sciences) is an FDA-approved stool test that combines stool DNA with a proprietary FIT component. One fair-quality diagnostic accuracy study (n = 9989) evaluated Cologuard compared with OC FIT-CHEK.83 In that study, Cologuard had a statistically significant higher sensitivity to detect CRC and advanced adenoma compared with OC FIT-CHEK. The higher sensitivity for CRC (92%; 95% CI, 84%-97%) and for advanced adenoma (42%; 95% CI, 39%-46%) was accompanied by lower specificity (84%; 95% CI, 84%-85% for CRC and 87%; 95% CI, 86%-87% for advanced adenoma). In our active surveillance of the literature, we identified 1 additional diagnostic accuracy study of FIT plus sDNA (n = 661) in asymptomatic Alaska Native adults.9 This study was not powered to find a difference in detection of CRC; nonetheless, findings were generally consistent with the included study on FIT plus sDNA.83

Harms of Screening

Key Question 3a. What are the adverse effects of the different screening tests (either as single application or in a screening program)?

Key Question 3b. Do adverse effects vary by important subpopulations (eg, age)?

Ninety-eight fair- or good-quality studies27,29,3739,45,48,64,66,77,78,81,82,8587,89,92,93,97,99,101,116191 in 113 articles27,29,34,3739,44,45,48,50,53,64,66,70,77,78,81,82,8587,89,92,93,97,99,101,114,116200 were included that evaluated the harms of CRC screening. These studies included 14 studies of screening programs using stool testing or SIG, 55 studies of colonoscopy in asymptomatic adults,37,45,77,78,85,97,101,116,117,119124,126,128131,133,136,140,142,144,147,148,150,151,153156,158,159,161163,170178,180183,187190 18 studies of screening SIG,27,38,39,43,48,50,66,143,146,151,157,162,176,183,185,186,191194,200 and 15 studies of screening CTC in asymptomatic adults.45,81,82,85,87,89,101,118,135,145,150,162,169,179 Twelve CTC studies provided estimates of radiation exposure per examination,81,82,8587,89,93,99,101,118,135,162 and another 21 CTC studies reported information on extracolonic findings.45,85,99,101,114,125,127,134,137139,141,150,152,160,164,166168,184,195,198

Endoscopy Harms

Approximately half of colonoscopy harms studies (29/55 studies) were in explicitly screening or asymptomatic populations (eTable 2 in the Supplement). By pooling 26 studies (n = 3 414 108) in screening populations or generally asymptomatic persons,37,45,77,78,85,97,101,120,121,124,126,130,131,136,150,156,163,170,174,176,180182,188190 it was estimated that the risk of perforations from colonoscopy was 4 in 10 000 procedures (95% CI, 2-5 in 10 000; I2 = 86%) (Figure 4). On the basis of 22 of those studies (n = 3 347 101),37,45,77,85,97,101,120,121,124,126,130,131,156,163,170,174,180182,188190 it was estimated that the risk of major bleeding from colonoscopy was 8 in 10 000 procedures (95% CI, 5-14 in 10 000; I2 = 97%) (Figure 5). Only eight studies (n = 204 614) explicitly reported if perforation or major bleeding was related to polypectomy or biopsy.45,85,120,136,158,173,177,178 Based on this limited subset of studies reporting adequate information, 36% (15/42) of perforations and 96% (49/51) of major bleeding events were from polypectomy.

All 18 SIG harms studies were conducted in general-risk screening populations (eTable 3 in the Supplement). Based on the results of 16 studies (n = 329 698),38,39,43,48,50,66,143,146,151,157,176,183,185,186,191,192 perforations from SIG in average-risk screening populations were relatively uncommon: the pooled point estimate was 1 in 10 000 procedures (95% CI, 0.4-1.4 in 10 000; I2 = 18.4%). In 10 studies (n = 137 987),27,38,48,50,66,143,146,157,185,186 major bleeding episodes from SIG were also relatively uncommon, with a pooled point estimate of 2 in 10 000 procedures (95% CI, 0.7-4 in 10 000; I2 = 52.5%) (Figure 6 and Figure 7). Flexible sigmoidoscopy, however, may require follow-up diagnostic or therapeutic colonoscopy. From 5 SIG screening trials, the pooled estimate was 14 perforations per 10 000 (95% CI, 9-26 in 10 000) and 34 major bleeds per 10 000 (95% CI, 5-63 in 10 000) for follow-up colonoscopy for positive screening SIG from 4 trials.

Other serious harms from endoscopy were not routinely reported or consistently defined. Only 2 studies compared harms other than perforation and bleeding in persons who had a colonoscopy vs those who had not.180,187 Both of these studies found no statistically significant higher risks of serious harms (including myocardial infarction, cerebrovascular accident, other cardiovascular events, and mortality) attributable to colonoscopy. Because of reporting bias around serious harms other than perforation and bleeding, as well as the lack of evidence for other serious harms attributable to colonoscopy in the few studies with control groups, these data were not quantitatively pooled.

Nineteen studies examined differential harms of colonoscopy by age group.116,119,122,123,128,129,131,136,140,154,156,159,161,170,172,174,187,189,190 These studies generally found increasing rates of serious adverse events with increasing age, including perforation and bleeding.

CTC Harms

Fifteen fair- or good-quality studies addressed serious adverse effects of screening CTC (eTable 4 in the Supplement).45,81,82,85,87,89,101,118,135,145,150,162,169,179 Evidence suggested little to no risk of serious adverse events, including perforation, from CTC based on 11 prospective studies (n = 10 272) performed in screening populations.45,81,82,85,87,89,101,118,135,145,150,162,169,179

Many of the CTC studies in this review did not report actual radiation exposure or provide sufficient information to calculate it. Based on 4 included diagnostic accuracy studies of CTC,81,82,85,101 the estimated radiation dose for 1 full-screening CTC examination (dual positioning supine and prone) was about 4.5 to 7 mSv. In 3 additional recent CTC screening studies118,135,162 (2004-2008), the estimated radiation dose decreased to a range of 1 to less than 5 mSv.

CTC Extracolonic Findings

Incidental extracolonic findings detected on CTC can be beneficial or harmful depending on the finding. Twenty-one studies (n = 38 293)45,85,99,101,125,127,134,137139,141,150,152,160,164,166168,184,195,198 in 22 articles45,85,99,101,114,125,127,134,137139,141,150,152,160,164,166168,184,195,198 (7 studies with overlapping populations reported different types extracolonic findings) reported on extracolonic findings in asymptomatic persons (eTable 5 in the Supplement). In general, these studies varied greatly in their ability to accurately assess follow-up and the duration of follow-up.

Overall, extracolonic findings were common, occurring in 27% to 69% of examinations. Similarly, the studies suggested a very wide range of findings needing additional workup: 5% to 37% had E3 or E4 findings, and 1.7% to 12% had E4 findings. Among the studies that also reported medical follow-up of extracolonic findings, 1.4% to 11% went on to diagnostic evaluation, which is similar to the prevalence of E4 category findings. Among studies that adequately reported subsequent treatment, only up to 3% required definitive medical or surgical treatment. Extracolonic cancers were not common, occurring in 0.5% of persons undergoing CTC examinations. In the largest series of examinations (n = 10 286), which had about 4 years of follow-up, 0.35% of examinations revealed an extracolonic malignancy, 32 of which received definitive treatment.167 Abdominal aortic aneurysms were identified in 1.4% of persons or fewer. In our active surveillance of the literature, we identified 1 additional study evaluating extracolonic findings in screening CTC (n = 7952).7 This study’s population overlapped with several already included studies and reported that 2.5% of examinations had E4 category findings, consistent with findings from included studies.150,164,166168,195,198

Discussion

Colorectal cancer screening continues to be a necessary and active field of research. Since the 2008 USPSTF recommendation was published, 95 new studies were identified, including more evidence on (1) the effectiveness of SIG for reducing CRC mortality, (2) the test performance of screening CTC and decreasing radiation exposure from CTC, and (3) the test performance of a number of FDA-approved FITs (including 1 FIT plus sDNA test). Colonoscopy, SIG, CTC, and stool testing (gFOBT, FIT, and FIT plus sDNA test) each have differing levels of evidence to support their use, ability to detect cancer and precursor lesions, and risk of serious adverse events in screening average-risk adults for CRC (Table 4).

To date, no CRC screening modality has been shown to reduce all-cause mortality. Robust data from well-conducted population-based screening RCTs have demonstrated that both Hemoccult II and SIG can reduce CRC mortality, although neither of these tests is widely used for screening in the United States. Therefore, the empirical data on the performance of CRC screening programs using modalities used in clinical practice today are limited. Expensive, large population-based RCTs of newer stool tests may not always be necessary, as evidence-based reasoning supports that screening with stool tests with sensitivity and specificity that are both as good as, or better than, Hemoccult II would result in CRC mortality reductions similar to or better than reductions shown in existing trials.201 Based on this review, stool tests that meet those requirements are available, including specific single-stool sample FITs. However, FITs are not homogenous: they use different assays and have different diagnostic performance levels. The FDA-approved OC-Light and OC FIT-CHEK tests have the most evidence to support their use. Stool tests that maximize sensitivity (eg, FIT plus sDNA test, multiple sample FITs, or quantitative FIT using lower cutoffs) have lower specificity and therefore need new trials or modeling exercises to understand the tradeoff of higher false-positive findings. In addition, stool tests vary in cost; for example, the Centers for Medicare & Medicaid Services reimbursement is $23 per FIT vs $493 per FIT plus sDNA test.202

Even though its superiority in a program of screening has not been empirically established, colonoscopy remains the criterion standard for assessing the test performance of other CRC screening tests. Quiz Ref IDMoreover, colonoscopy is significantly more invasive than other available tests and thus carries a greater possibility of procedural complications, as well as harms of overdiagnosis and overtreatment of smaller lesions (ie, <10 mm). Three large RCTs of screening colonoscopy in average-risk adults are under way and will provide information about the long-term CRC incidence and mortality outcomes: the Northern European Initiative on Colorectal Cancer (NordICC) trial, comparing screening colonoscopy with usual care (estimated primary completion date, June 2026)203; COLONPREV, comparing colonoscopy with biennial FIT in Spain (estimated primary completion date, November 2021)37,204,205; and CONFIRM, comparing colonoscopy vs annual FIT in the United States (estimated primary completion date, September 2027).206

Quiz Ref IDEvidence continues to accrue that CTC adequately detects CRC and large potential precursor lesions. Although the risk of immediate harms from screening CTC (eg, bowel perforation from insufflation) is very low, it is unclear what (if any) true harm is posed by cumulative exposure to low-dose radiation or detection of extracolonic findings. Although the radiation dose appears to be decreasing over time due to technological and protocol advancements, it still ranges as high as 7 mSv per examination (dual positioning). Given that the average amount of radiation one is exposed to from background sources in the United States is about 3 mSv per year,207 ionizing radiation from a single CTC examination is low. However, current expert recommendations are to repeat CTC every 5 years, and even low doses of ionizing radiation could cumulatively convey a small excess risk of cancer.208,209 From empirical evidence to date, it remains unclear whether detection of extracolonic findings represents a net benefit or harm.

Quiz Ref IDThis evidence report and systematic review did not address several important issues: screening in high-risk adults (ie, those with known family history of CRC), risk assessment to tailor screening, test acceptability, availability of or access to screening tests, methods to increase screening adherence, potential harms of overdiagnosis or unnecessary polypectomy, overuse or misuse of screening, and surveillance after adenoma detection. This review was commissioned along with a separate set of microsimulation decision models from the Cancer Intervention and Surveillance Modeling Network (CISNET) that addressed other important gaps in evidence, including ages to start and stop screening, screening intervals, and targeted or tailored screening.210 The review was limited to evidence conducted in countries with the highest applicability to US practice; in addition, only articles published in English were considered for inclusion.

Unlike other routinely recommended or conducted cancer screening, there are multiple viable options for CRC screening. These options have various levels of evidence to support their use, aims (eg, to detect cancers, potential precursor lesions, or both), test acceptability and adherence, intervals of time to repeat screening, need for follow-up testing (including surveillance incurred), associated serious harms, availability in practice, cost, and advocacy for their use. This complexity is compounded by testing whose quality is more operator-dependent (eg, colonoscopy, CTC), as well as rapid technologic advancements in improving existing tests or developing new tests.

Empirical studies, trials, or well-designed cohort studies with average-risk populations are still needed to evaluate programs of screening using colonoscopy, the best-performing stool tests, and effect of CTC on cancer mortality and cancer incidence. Also needed are studies of diagnostic accuracy to confirm the screening test performance of promising stool tests based on high sensitivity to detect CRC or advanced adenomas with thus far limited reproducibility (ie, only 1 study). Diagnostic accuracy studies, particularly those evaluating new or more complex technologies, should report percentages of inadequate or indeterminate results. It is also important to understand the contribution of technological advancements to existing technology (eg, enhancements to optical colonoscopy or CTC) on test performance in average-risk adults as well as on reducing harms (eg, decreasing radiation exposure, less aggressive bowel preparation). More complete and consistent reporting regarding downstream benefits and harms from initial detection (ie, subsequent workup and definitive treatment) of C-RADS E3 and E4 findings need to be published in observational studies or trials with longer-term follow-up. Data are still needed on the differential uptake of and adherence to screening modalities and on continued adherence to repeated rounds of screening and diagnostic follow-up to screening over longer periods.

Conclusions

Colonoscopy, flexible sigmoidoscopy, CTC, and various stool tests have differing levels of evidence to support their use in CRC screening, ability to detect CRC and precursor lesions, and risk of serious adverse events in average-risk adults. Although CRC screening has a large body of supporting evidence, additional research is still needed to weigh the relative benefits and harms of each test in within a program of screening.

Back to top
Article Information

Corresponding Author: Jennifer S. Lin, MD, MCR, Center for Health Research, Kaiser Permanente Northwest, 3800 N Interstate Ave, Portland, OR 97227 (jennifer.s.lin@kpchr.org).

Correction: This article was corrected online August 2, 2016, to fix an incomplete URL for the full report and on October 4, 2016, to fix alignment of a row in Table 3 and correct numbers in the gFOBT row in Table 4.

Published Online: June 15, 2016. doi:10.1001/jama.2016.3332

Author Contributions: Dr Lin had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Study concept and design: Lin, Piper, Perdue, Whitlock.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Lin, Piper, Rutter, Webber.

Critical revision of the manuscript for important intellectual content: Lin, Piper, Perdue, Rutter, O’Connor, Smith, Whitlock.

Statistical analysis: Lin, Piper, Rutter, O’Connor, Smith.

Obtained funding: Lin, Whitlock.

Administrative, technical, or material support: Piper, Perdue, Webber.

Study supervision: Lin, Whitlock.

Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported.

Funding/Support: This research was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the USPSTF.

Role of the Funder/Sponsor: Investigators worked with USPSTF members and AHRQ staff to develop the scope, analytic framework, and key questions for this review. AHRQ staff provided project oversight; reviewed the report to ensure that the analysis met methodological standards; and distributed the draft for peer review. AHRQ reviewed and approved the manuscript before submission, but had no role in the design and conduct of the study including study selection, quality assessment, analysis, and interpretation of the data; preparation of the manuscript; and decision to submit the manuscript for publication.

Additional Contributions: We gratefully acknowledge the following individuals for their contributions to this project: Smyth Lai, MLS; Kevin Lutz, MFA; and Elizabeth Hess, MA, ELS(D), at the Kaiser Permanente Center for Health Research; Jennifer Croswell, MD, MPH, at the Agency for Healthcare Research and Quality; and current and former members of the US Preventive Services Task Force who contributed to topic deliberations. USPSTF members, peer reviewers, and federal partner reviewers did not receive financial compensation for their contributions.

Additional Information: A draft version of this evidence report underwent external peer review from 6 content experts (James Allison, MD, University of California, San Francisco; Samir Gupta, MD, MSCS, University of California, San Diego; Theodore R. Levin, MD, Kaiser Permanente; David Lieberman, MD, Oregon Health & Science University; Perry Pickhardt, MD, MPH, University of Wisconsin; David Ransohoff, MD, University of North Carolina at Chapel Hill) and 4 federal partners: Centers for Disease Control and Prevention, National Institutes of Health, US Department of Veterans Affairs, and Indian Health Service. Comments were presented to the USPSTF during its deliberation of the evidence and were considered in preparing the final evidence review.

Editorial Disclaimer: This evidence report is presented as a document in support of the accompanying USPSTF Recommendation Statement. It did not undergo additional peer review after submission to JAMA.

References
1.
Cancer Facts and Figures 2013. American Cancer Society. http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2013/. Accessed May 24, 2016.
2.
Centers for Disease Control and Prevention (CDC).  Vital signs: colorectal cancer screening test use: United States, 2012. MMWR Morb Mortal Wkly Rep. 2013;62(44):881-888.
PubMed
3.
US Preventive Services Task Force.  Screening for colorectal cancer: US Preventive Services Task Force recommendation statement. Ann Intern Med. 2008;149(9):627-637.
PubMedArticle
4.
Levin  B, Lieberman  DA, McFarland  B,  et al; American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee.  Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58(3):130-160.
PubMedArticle
5.
Lin  JS, Piper  MA, Perdue  LA,  et al. Screening for Colorectal Cancer: A Systematic Evidence Review for the US Preventive Services Task Force: Evidence Synthesis No. 135. Rockville, MD: Agency for Healthcare Research and Quality; 2016. AHRQ publication 14-05203-EF-1.
6.
Whitlock  EP, Lin  J, Liles  E,  et al. Screening for Colorectal Cancer: An Updated Systematic Review. Rockville, MD: Agency for Healthcare Research and Quality; 2008.
7.
Pooler  BD, Kim  DH, Pickhardt  PJ.  Potentially important extracolonic findings at screening CT colonography: incidence and outcomes data from a clinical screening program. AJR Am J Roentgenol. 2016;206(2):313-318.
PubMedArticle
8.
Sali  L, Mascalchi  M, Falchini  M,  et al; SAVE Study Investigators.  Reduced and full-preparation CT colonography, fecal immunochemical test, and colonoscopy for population screening of colorectal cancer: a randomized trial. J Natl Cancer Inst. 2015;108(2):108.
PubMed
9.
Redwood  DG, Asay  ED, Blake  ID,  et al.  Stool DNA testing for screening detection of colorectal neoplasia in Alaska Native people. Mayo Clin Proc. 2016;91(1):61-70.
PubMedArticle
10.
Lijmer  JG, Mol  BW, Heisterkamp  S,  et al.  Empirical evidence of design-related bias in studies of diagnostic tests. JAMA. 1999;282(11):1061-1066.
PubMedArticle
11.
Whiting  P, Rutjes  AW, Reitsma  JB, Glas  AS, Bossuyt  PM, Kleijnen  J.  Sources of variation and bias in studies of diagnostic accuracy: a systematic review. Ann Intern Med. 2004;140(3):189-202.
PubMedArticle
12.
Leeflang  MM, Bossuyt  PM, Irwig  L.  Diagnostic test accuracy may vary with prevalence: implications for evidence-based diagnosis. J Clin Epidemiol. 2009;62(1):5-12.
PubMedArticle
13.
Ransohoff  DF, Feinstein  AR.  Problems of spectrum and bias in evaluating the efficacy of diagnostic tests. N Engl J Med. 1978;299(17):926-930.
PubMedArticle
14.
Rutjes  AW, Reitsma  JB, Di Nisio  M, Smidt  N, van Rijn  JC, Bossuyt  PM.  Evidence of bias and variation in diagnostic accuracy studies. CMAJ. 2006;174(4):469-476.
PubMedArticle
15.
Zalis  ME, Barish  MA, Choi  JR,  et al; Working Group on Virtual Colonoscopy.  CT colonography reporting and data system: a consensus proposal. Radiology. 2005;236(1):3-9.
PubMedArticle
16.
Harris  RP, Helfand  M, Woolf  SH,  et al; Methods Work Group, Third US Preventive Services Task Force.  Current methods of the US Preventive Services Task Force: a review of the process. Am J Prev Med. 2001;20(3)(suppl):21-35.
PubMedArticle
17.
National Institute for Health and Clinical Excellence. The Guidelines Manual. London, UK: National Institute for Health and Clinical Excellence; 2006.
18.
Shea  BJ, Grimshaw  JM, Wells  GA,  et al.  Development of AMSTAR: a measurement tool to assess the methodological quality of systematic reviews. BMC Med Res Methodol. 2007;7:10.
PubMedArticle
19.
Wells  GA, Shea  B, O’Connell  D,  et al. The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analysis. Ottawa Hospital Research Institute. http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp. Accessed May 25, 2016.
20.
Whiting  P, Rutjes  AW, Reitsma  JB, Bossuyt  PM, Kleijnen  J.  The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25.
PubMedArticle
21.
Whiting  PF, Rutjes  AW, Westwood  ME,  et al; QUADAS-2 Group.  QUADAS-2: a revised tool for the quality assessment of diagnostic accuracy studies. Ann Intern Med. 2011;155(8):529-536.
PubMedArticle
22.
Hardy  RJ, Thompson  SG.  A likelihood approach to meta-analysis with random effects. Stat Med. 1996;15(6):619-629.
PubMedArticle
23.
Thompson  SG, Sharp  SJ.  Explaining heterogeneity in meta-analysis: a comparison of methods. Stat Med. 1999;18(20):2693-2708.
PubMedArticle
24.
Guolo A, Varin C. Package metaLik. https://cran.r-project.org/web/packages/metaLik/index.html. Accessed May 25, 2016.
25.
Atkin  WS, Edwards  R, Kralj-Hans  I,  et al; UK Flexible Sigmoidoscopy Trial Investigators.  Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet. 2010;375(9726):1624-1633.
PubMedArticle
26.
Berry  DP, Clarke  P, Hardcastle  JD, Vellacott  KD.  Randomized trial of the addition of flexible sigmoidoscopy to faecal occult blood testing for colorectal neoplasia population screening. Br J Surg. 1997;84(9):1274-1276.
PubMedArticle
27.
Brevinge  H, Lindholm  E, Buntzen  S, Kewenter  J.  Screening for colorectal neoplasia with faecal occult blood testing compared with flexible sigmoidoscopy directly in a 55-56 years’ old population. Int J Colorectal Dis. 1997;12(5):291-295.
PubMedArticle
28.
Faivre  J, Dancourt  V, Denis  B,  et al.  Comparison between a guaiac and three immunochemical faecal occult blood tests in screening for colorectal cancer. Eur J Cancer. 2012;48(16):2969-2976.
PubMedArticle
29.
Faivre  J, Dancourt  V, Lejeune  C,  et al.  Reduction in colorectal cancer mortality by fecal occult blood screening in a French controlled study. Gastroenterology. 2004;126(7):1674-1680.
PubMedArticle
30.
Guittet  L, Bouvier  V, Mariotte  N,  et al.  Comparison of a guaiac and an immunochemical faecal occult blood test for the detection of colonic lesions according to lesion type and location. Br J Cancer. 2009;100(8):1230-1235.
PubMedArticle
31.
Hamza  S, Dancourt  V, Lejeune  C, Bidan  JM, Lepage  C, Faivre  J.  Diagnostic yield of a one sample immunochemical test at different cut-off values in an organised screening programme for colorectal cancer. Eur J Cancer. 2013;49(12):2727-2733.
PubMedArticle
32.
Hol  L, van Leerdam  ME, van Ballegooijen  M,  et al.  Screening for colorectal cancer: randomised trial comparing guaiac-based and immunochemical faecal occult blood testing and flexible sigmoidoscopy. Gut. 2010;59(1):62-68.
PubMedArticle
33.
Kronborg  O, Jørgensen  OD, Fenger  C, Rasmussen  M.  Randomized study of biennial screening with a faecal occult blood test: results after nine screening rounds. Scand J Gastroenterol. 2004;39(9):846-851.
PubMedArticle
34.
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(8):1029-1036.
PubMedArticle
35.
Malila  N, Palva  T, Malminiemi  O,  et al.  Coverage and performance of colorectal cancer screening with the faecal occult blood test in Finland. J Med Screen. 2011;18(1):18-23.
PubMedArticle
36.
Nishihara  R, Wu  K, Lochhead  P,  et al.  Long-term colorectal-cancer incidence and mortality after lower endoscopy. N Engl J Med. 2013;369(12):1095-1105.
PubMedArticle
37.
Quintero  E, Castells  A, Bujanda  L,  et al; COLONPREV Study Investigators.  Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening. N Engl J Med. 2012;366(8):697-706.
PubMedArticle
38.
Rasmussen  M, Kronborg  O, Fenger  C, Jørgensen  OD.  Possible advantages and drawbacks of adding flexible sigmoidoscopy to Hemoccult-II in screening for colorectal cancer: a randomized study. Scand J Gastroenterol. 1999;34(1):73-78.
PubMedArticle
39.
Schoen  RE, Pinsky  PF, Weissfeld  JL,  et al; PLCO Project Team.  Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366(25):2345-2357.
PubMedArticle
40.
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;61(7):1036-1040.
PubMedArticle
41.
Segnan  N, Armaroli  P, Bonelli  L,  et al; SCORE Working Group.  Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial: SCORE. J Natl Cancer Inst. 2011;103(17):1310-1322.
PubMedArticle
42.
Segnan  N, Senore  C, Andreoni  B,  et al; SCORE3 Working Group-Italy.  Comparing attendance and detection rate of colonoscopy with sigmoidoscopy and FIT for colorectal cancer screening. Gastroenterology. 2007;132(7):2304-2312.
PubMedArticle
43.
Segnan  N, Senore  C, Andreoni  B,  et al; SCORE2 Working Group-Italy.  Randomized trial of different screening strategies for colorectal cancer: patient response and detection rates. J Natl Cancer Inst. 2005;97(5):347-357.
PubMedArticle
44.
Shaukat  A, Mongin  SJ, Geisser  MS,  et al.  Long-term mortality after screening for colorectal cancer. N Engl J Med. 2013;369(12):1106-1114.
PubMedArticle
45.
Stoop  EM, de Haan  MC, de Wijkerslooth  TR,  et al.  Participation and yield of colonoscopy versus non-cathartic CT colonography in population-based screening for colorectal cancer: a randomised controlled trial. Lancet Oncol. 2012;13(1):55-64.
PubMedArticle
46.
van Roon  AH, Goede  SL, van Ballegooijen  M,  et al.  Random comparison of repeated faecal immunochemical testing at different intervals for population-based colorectal cancer screening. Gut. 2013;62(3):409-415.
PubMedArticle
47.
van Rossum  LG, van Rijn  AF, Laheij  RJ,  et al.  Random comparison of guaiac and immunochemical fecal occult blood tests for colorectal cancer in a screening population. Gastroenterology. 2008;135(1):82-90.
PubMedArticle
48.
Verne  JECW, Aubrey  R, Love  SB, Talbot  IC, Northover  JM.  Population based randomized study of uptake and yield of screening by flexible sigmoidoscopy compared with screening by faecal occult blood testing. BMJ. 1998;317(7152):182-185.
PubMedArticle
49.
Zubero  MB, Arana-Arri  E, Pijoan  JI,  et al.  Population-based colorectal cancer screening: comparison of two fecal occult blood test. Front Pharmacol. 2014;4:175.
PubMedArticle
50.
Atkin  WS, Cook  CF, Cuzick  J, Edwards  R, Northover  JM, Wardle  J; UK Flexible Sigmoidoscopy Screening Trial Investigators.  Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet. 2002;359(9314):1291-1300.
PubMedArticle
51.
Atkin  WS, Cuzick  J, Northover  JM, Whynes  DK.  Prevention of colorectal cancer by once-only sigmoidoscopy. Lancet. 1993;341(8847):736-740.
PubMedArticle
52.
Bretthauer  M, Gondal  G, Larsen  K,  et al.  Design, organization and management of a controlled population screening study for detection of colorectal neoplasia: attendance rates in the NORCCAP study (Norwegian Colorectal Cancer Prevention). Scand J Gastroenterol. 2002;37(5):568-573.
PubMedArticle
53.
de Wijkerslooth  TR, de Haan  MC, Stoop  EM,  et al.  Study protocol: population screening for colorectal cancer by colonoscopy or CT colonography: a randomized controlled trial. BMC Gastroenterol. 2010;10:47.
PubMedArticle
54.
Denters  MJ, Deutekom  M, Bossuyt  PM, Stroobants  AK, Fockens  P, Dekker  E.  Lower risk of advanced neoplasia among patients with a previous negative result from a fecal test for colorectal cancer. Gastroenterology. 2012;142(3):497-504.
PubMedArticle
55.
Denters  MJ, Deutekom  M, Fockens  P, Bossuyt  PM, Dekker  E.  Implementation of population screening for colorectal cancer by repeated fecal occult blood test in the Netherlands. BMC Gastroenterol. 2009;9:28.
PubMedArticle
56.
Faivre  J, Dancourt  V, Manfredi  S,  et al.  Positivity rates and performances of immunochemical faecal occult blood tests at different cut-off levels within a colorectal cancer screening programme. Dig Liver Dis. 2012;44(8):700-704.
PubMedArticle
57.
Guittet  L, Bouvier  V, Guillaume  E,  et al.  Colorectal cancer screening: why immunochemical faecal occult blood test performs as well with either one or two samples. Dig Liver Dis. 2012;44(8):694-699.
PubMedArticle
58.
Guittet  L, Bouvier  V, Mariotte  N,  et al.  Performance of immunochemical faecal occult blood test in colorectal cancer screening in average-risk population according to positivity threshold and number of samples. Int J Cancer. 2009;125(5):1127-1133.
PubMedArticle
59.
Hardcastle  JD, Chamberlain  JO, Robinson  MH,  et al.  Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet. 1996;348(9040):1472-1477.
PubMedArticle
60.
Holme  Ø, Løberg  M, Kalager  M,  et al.  Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality: a randomized clinical trial. JAMA. 2014;312(6):606-615.
PubMedArticle
61.
Kewenter  J, Brevinge  H, Engarås  B, Haglind  E, Ahrén  C.  Results of screening, rescreening, and follow-up in a prospective randomized study for detection of colorectal cancer by fecal occult blood testing: results for 68,308 subjects. Scand J Gastroenterol. 1994;29(5):468-473.
PubMedArticle
62.
Malila  N, Oivanen  T, Malminiemi  O, Hakama  M.  Test, episode, and programme sensitivities of screening for colorectal cancer as a public health policy in Finland: experimental design. BMJ. 2008;337:a2261.
PubMedArticle
63.
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(22):1603-1607.
PubMedArticle
64.
Mandel  JS, Bond  JH, Church  TR,  et al.  Reducing mortality from colorectal cancer by screening for fecal occult blood: Minnesota Colon Cancer Control Study. N Engl J Med. 1993;328(19):1365-1371.
PubMedArticle
65.
Parra-Blanco  A, Nicolas-Perez  D, Gimeno-Garcia  A,  et al.  The timing of bowel preparation before colonoscopy determines the quality of cleansing, and is a significant factor contributing to the detection of flat lesions: a randomized study. World J Gastroenterol. 2006;12(38):6161-6166.
PubMedArticle
66.
Segnan  N, Senore  C, Andreoni  B,  et al; SCORE Working Group-Italy.  Baseline findings of the Italian multicenter randomized controlled trial of “once-only sigmoidoscopy”: SCORE. J Natl Cancer Inst. 2002;94(23):1763-1772.
PubMedArticle
67.
Thomas  W, White  CM, Mah  J, Geisser  MS, Church  TR, Mandel  JS.  Longitudinal compliance with annual screening for fecal occult blood: Minnesota Colon Cancer Control Study. Am J Epidemiol. 1995;142(2):176-182.
PubMed
68.
Atkin  WS, Cook  CF, Cuzick  J, Edwards  R, Northover  JM, Wardle  J; UK Flexible Sigmoidoscopy Screening Trial Investigators.  Single flexible sigmoidoscopy screening to prevent colorectal cancer: baseline findings of a UK multicentre randomised trial. Lancet. 2002;359(9314):1291-1300.
PubMedArticle
69.
van Roon  AH, Wilschut  JA, Hol  L,  et al.  Diagnostic yield improves with collection of 2 samples in fecal immunochemical test screening without affecting attendance. Clin Gastroenterol Hepatol. 2011;9(4):333-339.
PubMedArticle
70.
van Dam  L, de Wijkerslooth  TR, de Haan  MC,  et al.  Time requirements and health effects of participation in colorectal cancer screening with colonoscopy or computed tomography colonography in a randomized controlled trial. Endoscopy. 2013;45(3):182-188.
PubMedArticle
71.
Weissfeld  JL, Schoen  RE, Pinsky  PF,  et al; PLCO Project Team.  Flexible sigmoidoscopy in the PLCO cancer screening trial: results from the baseline screening examination of a randomized trial. J Natl Cancer Inst. 2005;97(13):989-997.
PubMedArticle
72.
Allison  JE, Sakoda  LC, Levin  TR,  et al.  Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst. 2007;99(19):1462-1470.
PubMedArticle
73.
Allison  JE, Tekawa  IS, Ransom  LJ, Adrain  AL.  A comparison of fecal occult-blood tests for colorectal-cancer screening. N Engl J Med. 1996;334(3):155-159.
PubMedArticle
74.
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;49(14):3049-3054.
PubMedArticle
75.
Castiglione  G, Visioli  CB, Ciatto  S,  et al.  Sensitivity of latex agglutination faecal occult blood test in the Florence District population-based colorectal cancer screening programme. Br J Cancer. 2007;96(11):1750-1754.
PubMedArticle
76.
Chen  LS, Yen  AM, Chiu  SY, Liao  CS, Chen  HH.  Baseline faecal occult blood concentration as a predictor of incident colorectal neoplasia: longitudinal follow-up of a Taiwanese population-based colorectal cancer screening cohort. Lancet Oncol. 2011;12(6):551-558.
PubMedArticle
77.
Cheng  TI, Wong  JM, Hong  CF,  et al.  Colorectal cancer screening in asymptomatic adults: comparison of colonoscopy, sigmoidoscopy and fecal occult blood tests. J Formos Med Assoc. 2002;101(10):685-690.
PubMed
78.
Chiu  HM, Lee  YC, Tu  CH,  et al.  Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test. Clin Gastroenterol Hepatol. 2013;11(7):832-8.e1,2.
PubMedArticle
79.
Church  TR, Wandell  M, Lofton-Day  C,  et al; PRESEPT Clinical Study Steering Committee, Investigators and Study Team.  Prospective evaluation of methylated SEPT9 in plasma for detection of asymptomatic colorectal cancer. Gut. 2014;63(2):317-325.
PubMedArticle
80.
de Wijkerslooth  TR, Stoop  EM, Bossuyt  PM,  et al.  Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia. Am J Gastroenterol. 2012;107(10):1570-1578.
PubMedArticle
81.
Fletcher  JG, Silva  AC, Fidler  JL,  et al.  Noncathartic CT colonography: image quality assessment and performance and in a screening cohort. AJR Am J Roentgenol. 2013;201(4):787-794.
PubMedArticle
82.
Graser  A, Stieber  P, Nagel  D,  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;58(2):241-248.
PubMedArticle
83.
Imperiale  TF, Ransohoff  DF, Itzkowitz  SH,  et al.  Multitarget stool DNA testing for colorectal-cancer screening. N Engl J Med. 2014;370(14):1287-1297.
PubMedArticle
84.
Itoh  M, Takahashi  K, Nishida  H, Sakagami  K, Okubo  T.  Estimation of the optimal cut off point in a new immunological faecal occult blood test in a corporate colorectal cancer screening programme. J Med Screen. 1996;3(2):66-71.
PubMed
85.
Johnson  CD, Chen  MH, Toledano  AY,  et al.  Accuracy of CT colonography for detection of large adenomas and cancers. N Engl J Med. 2008;359(12):1207-1217.
PubMedArticle
86.
Johnson  CD, Fletcher  JG, MacCarty  RL,  et al.  Effect of slice thickness and primary 2D versus 3D virtual dissection on colorectal lesion detection at CT colonography in 452 asymptomatic adults. AJR Am J Roentgenol. 2007;189(3):672-680.
PubMedArticle
87.
Kim  YS, Kim  N, Kim  SH,  et al.  The efficacy of intravenous contrast-enhanced 16-raw multidetector CT colonography for detecting patients with colorectal polyps in an asymptomatic population in Korea. J Clin Gastroenterol. 2008;42(7):791-798.
PubMedArticle
88.
Launoy  GD, Bertrand  HJ, Berchi  C,  et al.  Evaluation of an immunochemical fecal occult blood test with automated reading in screening for colorectal cancer in a general average-risk population. Int J Cancer. 2005;115(3):493-496.
PubMedArticle
89.
Lefere  P, Silva  C, Gryspeerdt  S,  et al.  Teleradiology based CT colonography to screen a population group of a remote island; at average risk for colorectal cancer. Eur J Radiol. 2013;82(6):e262-e267.
PubMedArticle
90.
Levi  Z, Birkenfeld  S, Vilkin  A,  et al.  A higher detection rate for colorectal cancer and advanced adenomatous polyp for screening with immunochemical fecal occult blood test than guaiac fecal occult blood test, despite lower compliance rate: a prospective, controlled, feasibility study. Int J Cancer. 2011;128(10):2415-2424.
PubMedArticle
91.
Levy  BT, Bay  C, Xu  Y,  et al.  Test characteristics of faecal immunochemical tests (FIT) compared with optical colonoscopy. J Med Screen. 2014;21(3):133-143.
PubMedArticle
92.
Lin  JS, Webber  EM, Beil  TL, Goddard  KA, Whitlock  EP. Fecal DNA Testing in Screening for Colorectal Cancer in Average-Risk Adults. Rockville, MD: Agency for Healthcare Research and Quality; 2012. AHRQ publication 12-EHC022-EF.
93.
Macari  M, Bini  EJ, Jacobs  SL,  et al.  Colorectal polyps and cancers in asymptomatic average-risk patients: evaluation with CT colonography. Radiology. 2004;230(3):629-636.
PubMedArticle
94.
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;129(2):422-428.
PubMedArticle
95.
Nakama  H, Yamamoto  M, Kamijo  N,  et al.  Colonoscopic evaluation of immunochemical fecal occult blood test for detection of colorectal neoplasia. Hepatogastroenterology. 1999;46(25):228-231.
PubMed
96.
Nakama  H, Kamijo  N, Abdul Fattah  AS, Zhang  B.  Validity of immunochemical faecal occult blood screening for colorectal cancer: a follow up study. J Med Screen. 1996;3(2):63-65.
PubMed
97.
Ng  SC, Ching  JY, Chan  V,  et al.  Diagnostic accuracy of faecal immunochemical test for screening individuals with a family history of colorectal cancer. Aliment Pharmacol Ther. 2013;38(7):835-841.
PubMedArticle
98.
Park  DI, Ryu  S, Kim  YH,  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;105(9):2017-2025.
PubMedArticle
99.
Pickhardt  PJ, Choi  JR, Hwang  I,  et al.  Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults. N Engl J Med. 2003;349(23):2191-2200.
PubMedArticle
100.
Sohn  DK, Jeong  SY, Choi  HS,  et al.  Single immunochemical fecal occult blood test for detection of colorectal neoplasia. Cancer Res Treat. 2005;37(1):20-23.
PubMedArticle
101.
Zalis  ME, Blake  MA, Cai  W,  et al.  Diagnostic accuracy of laxative-free computed tomographic colonography for detection of adenomatous polyps in asymptomatic adults: a prospective evaluation. Ann Intern Med. 2012;156(10):692-702.
PubMedArticle
102.
Chiang  TH, Chuang  SL, Chen  SL,  et al.  Difference in performance of fecal immunochemical tests with the same hemoglobin cutoff concentration in a nationwide colorectal cancer screening program. Gastroenterology. 2014;147(6):1317-1326.
PubMedArticle
103.
Hernandez  V, Cubiella  J, Gonzalez-Mao  MC,  et al; COLONPREV Study Investigators.  Fecal immunochemical test accuracy in average-risk colorectal cancer screening. World J Gastroenterol. 2014;20(4):1038-1047.
PubMedArticle
104.
Lee  YH, Hur  M, Kim  H,  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;53(3):e69-e71.
PubMedArticle
105.
Cologuard summary of safety and effectiveness data (SSED). US Food and Drug Administration. http://www.accessdata.fda.gov/cdrh_docs/pdf13/P130017b.pdf. Accessed May 25, 2016.
106.
Ahlquist  DA, Sargent  DJ, Loprinzi  CL,  et al.  Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann Intern Med. 2008;149(7):441-450,W81.
PubMedArticle
107.
Brenner  H, Haug  U, Hundt  S.  Inter-test agreement and quantitative cross-validation of immunochromatographical fecal occult blood tests. Int J Cancer. 2010;127(7):1643-1649.
PubMedArticle
108.
Brenner  H, Haug  U, Hundt  S.  Sex differences in performance of fecal occult blood testing. Am J Gastroenterol. 2010;105(11):2457-2464.
PubMedArticle
109.
Grazzini  G, Castiglione  G, Ciabattoni  C,  et al.  Colorectal cancer screening programme by faecal occult blood test in Tuscany: first round results. Eur J Cancer Prev. 2004;13(1):19-26.
PubMedArticle
110.
Haug  U, Kuntz  KM, Knudsen  AB, Hundt  S, Brenner  H.  Sensitivity of immunochemical faecal occult blood testing for detecting left- vs right-sided colorectal neoplasia. Br J Cancer. 2011;104(11):1779-1785.
PubMedArticle
111.
Haug  U, Hillebrand  T, Bendzko  P,  et al.  Mutant-enriched PCR and allele-specific hybridization reaction to detect K-ras mutations in stool DNA: high prevalence in a large sample of older adults. Clin Chem. 2007;53(4):787-790.
PubMedArticle
112.
Hundt  S, Haug  U, Brenner  H.  Comparative evaluation of immunochemical fecal occult blood tests for colorectal adenoma detection. Ann Intern Med. 2009;150(3):162-169.
PubMedArticle
113.
Imperiale  TF, Ransohoff  DF, Itzkowitz  SH, Turnbull  BA, Ross  ME; Colorectal Cancer Study Group.  Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 2004;351(26):2704-2714.
PubMedArticle
114.
Johnson  CD, Herman  BA, Chen  MH,  et al.  The National CT Colonography Trial: assessment of accuracy in participants 65 years of age and older. Radiology. 2012;263(2):401-408.
PubMedArticle
115.
Morikawa  T, Kato  J, Yamaji  Y,  et al.  Sensitivity of immunochemical fecal occult blood test to small colorectal adenomas. Am J Gastroenterol. 2007;102(10):2259-2264.
PubMedArticle
116.
Adeyemo  A, Bannazadeh  M, Riggs  T, Shellnut  J, Barkel  D, Wasvary  H.  Does sedation type affect colonoscopy perforation rates? Dis Colon Rectum. 2014;57(1):110-114.
PubMedArticle
117.
Adler  A, Wegscheider  K, Lieberman  D,  et al.  Factors determining the quality of screening colonoscopy: a prospective study on adenoma detection rates, from 12,134 examinations (Berlin colonoscopy project 3, BECOP-3). Gut. 2013;62(2):236-241.
PubMedArticle
118.
An  S, Lee  KH, Kim  YH,  et al.  Screening CT colonography in an asymptomatic average-risk Asian population: a 2-year experience in a single institution. AJR Am J Roentgenol. 2008;191(3):W100-W106.
PubMedArticle
119.
Arora  G, Mannalithara  A, Singh  G, Gerson  LB, Triadafilopoulos  G.  Risk of perforation from a colonoscopy in adults: a large population-based study. Gastrointest Endosc. 2009;69(3 pt 2):654-664.
PubMedArticle
120.
Bair  D, Pham  J, Seaton  MB, Arya  N, Pryce  M, Seaton  TL.  The quality of screening colonoscopies in an office-based endoscopy clinic. Can J Gastroenterol. 2009;23(1):41-47.
PubMedArticle
121.
Berhane  C, Denning  D.  Incidental finding of colorectal cancer in screening colonoscopy and its cost effectiveness. Am Surg. 2009;75(8):699-703.
PubMed
122.
Bielawska  B, Day  AG, Lieberman  DA, Hookey  LC.  Risk factors for early colonoscopic perforation include non-gastroenterologist endoscopists: a multivariable analysis. Clin Gastroenterol Hepatol. 2014;12(1):85-92.
PubMedArticle
123.
Blotière  PO, Weill  A, Ricordeau  P, Alla  F, Allemand  H.  Perforations and haemorrhages after colonoscopy in 2010: a study based on comprehensive French health insurance data (SNIIRAM). Clin Res Hepatol Gastroenterol. 2014;38(1):112-117.
PubMedArticle
124.
Bokemeyer  B, Bock  H, Hüppe  D,  et al.  Screening colonoscopy for colorectal cancer prevention: results from a German online registry on 269000 cases. Eur J Gastroenterol Hepatol. 2009;21(6):650-655.
PubMedArticle
125.
Cash  BD, Riddle  MS, Bhattacharya  I,  et al.  CT colonography of a Medicare-aged population: outcomes observed in an analysis of more than 1400 patients. AJR Am J Roentgenol. 2012;199(1):W27-W34.
PubMedArticle
126.
Castro  G, Azrak  MF, Seeff  LC, Royalty  J.  Outpatient colonoscopy complications in the CDC’s Colorectal Cancer Screening Demonstration Program: a prospective analysis. Cancer. 2013;119(suppl 15):2849-2854.
PubMedArticle
127.
Chin  M, Mendelson  R, Edwards  J, Foster  N, Forbes  G.  Computed tomographic colonography: prevalence, nature, and clinical significance of extracolonic findings in a community screening program. Am J Gastroenterol. 2005;100(12):2771-2776.
PubMedArticle
128.
Chukmaitov  A, Bradley  CJ, Dahman  B, Siangphoe  U, Warren  JL, Klabunde  CN.  Association of polypectomy techniques, endoscopist volume, and facility type with colonoscopy complications. Gastrointest Endosc. 2013;77(3):436-446.
PubMedArticle
129.
Cooper  GS, Kou  TD, Rex  DK.  Complications following colonoscopy with anesthesia assistance: a population-based analysis. JAMA Intern Med. 2013;173(7):551-556.
PubMedArticle
130.
Cotterill  M, Gasparelli  R, Kirby  E.  Colorectal cancer detection in a rural community: development of a colonoscopy screening program. Can Fam Physician. 2005;51:1224-1228.
PubMed
131.
Crispin  A, Birkner  B, Munte  A, Nusko  G, Mansmann  U.  Process quality and incidence of acute complications in a series of more than 230,000 outpatient colonoscopies. Endoscopy. 2009;41(12):1018-1025.
PubMedArticle
132.
Dancourt  V, Lejeune  C, Lepage  C, Gailliard  MC, Meny  B, Faivre  J.  Immunochemical faecal occult blood tests are superior to guaiac-based tests for the detection of colorectal neoplasms. Eur J Cancer. 2008;44(15):2254-2258.
PubMedArticle
133.
Dominitz  JA, Baldwin  LM, Green  P, Kreuter  WI, Ko  CW.  Regional variation in anesthesia assistance during outpatient colonoscopy is not associated with differences in polyp detection or complication rates. Gastroenterology. 2013;144(2):298-306.
PubMedArticle
134.
Durbin  JM, Stroup  SP, Altamar  HO, L’esperance  JO, Lacey  DR, Auge  BK.  Genitourinary abnormalities in an asymptomatic screening population: findings on virtual colonoscopy. Clin Nephrol. 2012;77(3):204-210.
PubMedArticle
135.
Edwards  JT, Mendelson  RM, Fritschi  L,  et al.  Colorectal neoplasia screening with CT colonography in average-risk asymptomatic subjects: community-based study. Radiology. 2004;230(2):459-464.
PubMedArticle
136.
Ferlitsch  M, Reinhart  K, Pramhas  S,  et al.  Sex-specific prevalence of adenomas, advanced adenomas, and colorectal cancer in individuals undergoing screening colonoscopy. JAMA. 2011;306(12):1352-1358.
PubMedArticle
137.
Flicker  MS, Tsoukas  AT, Hazra  A, Dachman  AH.  Economic impact of extracolonic findings at computed tomographic colonography. J Comput Assist Tomogr. 2008;32(4):497-503.
PubMedArticle
138.
Ginnerup Pedersen  B, Rosenkilde  M, Christiansen  TE, Laurberg  S.  Extracolonic findings at computed tomography colonography are a challenge. Gut. 2003;52(12):1744-1747.
PubMedArticle
139.
Gluecker  TM, Johnson  CD, Wilson  LA,  et al.  Extracolonic findings at CT colonography: evaluation of prevalence and cost in a screening population. Gastroenterology. 2003;124(4):911-916.
PubMedArticle
140.
Hamdani  U, Naeem  R, Haider  F,  et al.  Risk factors for colonoscopic perforation: a population-based study of 80118 cases. World J Gastroenterol. 2013;19(23):3596-3601.
PubMedArticle
141.
Hara  AK, Johnson  CD, MacCarty  RL, Welch  TJ.  Incidental extracolonic findings at CT colonography. Radiology. 2000;215(2):353-357.
PubMedArticle
142.
Ho  JM, Gruneir  A, Fischer  HD,  et al.  Serious events in older Ontario residents receiving bowel preparations for outpatient colonoscopy with various comorbidity profiles: a descriptive, population-based study. Can J Gastroenterol. 2012;26(7):436-440.
PubMedArticle
143.
Hoff  G, Thiis-Evensen  E, Grotmol  T, Sauar  J, Vatn  MH, Moen  IE.  Do undesirable effects of screening affect all-cause mortality in flexible sigmoidoscopy programmes? experience from the Telemark Polyp Study 1983-1996. Eur J Cancer Prev. 2001;10(2):131-137.
PubMedArticle
144.
Hsieh  TK, Hung  L, Kang  FC, Lan  KM, Poon  PW, So  EC.  Anesthesia does not increase the rate of bowel perforation during colonoscopy: a retrospective study. Acta Anaesthesiol Taiwan. 2009;47(4):162-166.
PubMedArticle
145.
Iafrate  F, Iussich  G, Correale  L,  et al.  Adverse events of computed tomography colonography: an Italian National Survey. Dig Liver Dis. 2013;45(8):645-650.
PubMedArticle
146.
Jain  A, Falzarano  J, Jain  A, Decker  R, Okubo  G, Fujiwara  D.  Outcome of 5,000 flexible sigmoidoscopies done by nurse endoscopists for colorectal screening in asymptomatic patients. Hawaii Med J. 2002;61(6):118-120.
PubMed
147.
Kamath  AS, Iqbal  CW, Sarr  MG,  et al.  Colonoscopic splenic injuries: incidence and management. J Gastrointest Surg. 2009;13(12):2136-2140.
PubMedArticle
148.
Kang  HY, Kang  HW, Kim  SG,  et al.  Incidence and management of colonoscopic perforations in Korea. Digestion. 2008;78(4):218-223.
PubMedArticle
149.
Kao  KT, Jain  A, Sheinbaum  A.  Ischemic colitis following routine screening colonoscopy: a case report. Endoscopy. 2009;41(suppl 2):E100.
PubMedArticle
150.
Kim  DH, Pickhardt  PJ, Taylor  AJ,  et al.  CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med. 2007;357(14):1403-1412.
PubMedArticle
151.
Kim  JS, Kim  BW, Kim  JI,  et al.  Endoscopic clip closure versus surgery for the treatment of iatrogenic colon perforations developed during diagnostic colonoscopy: a review of 115,285 patients. Surg Endosc. 2013;27(2):501-504.
PubMedArticle
152.
Kim  YS, Kim  N, Kim  SY,  et al.  Extracolonic findings in an asymptomatic screening population undergoing intravenous contrast-enhanced computed tomography colonography. J Gastroenterol Hepatol. 2008;23(7 pt 2):e49-e57.
PubMedArticle
153.
Ko  CW, Riffle  S, Shapiro  JA,  et al.  Incidence of minor complications and time lost from normal activities after screening or surveillance colonoscopy. Gastrointest Endosc. 2007;65(4):648-656.
PubMedArticle
154.
Korman  LY, Overholt  BF, Box  T, Winker  CK.  Perforation during colonoscopy in endoscopic ambulatory surgical centers. Gastrointest Endosc. 2003;58(4):554-557.
PubMedArticle
155.
Layton  JB, Klemmer  PJ, Christiansen  CF,  et al.  Sodium phosphate does not increase risk for acute kidney injury after routine colonoscopy, compared with polyethylene glycol. Clin Gastroenterol Hepatol. 2014;12(9):1514-1521.
PubMedArticle
156.
Levin  TR, Zhao  W, Conell  C,  et al.  Complications of colonoscopy in an integrated health care delivery system. Ann Intern Med. 2006;145(12):880-886.
PubMedArticle
157.
Levin  TR, Conell  C, Shapiro  JA, Chazan  SG, Nadel  MR, Selby  JV.  Complications of screening flexible sigmoidoscopy. Gastroenterology. 2002;123(6):1786-1792.
PubMedArticle
158.
Loffeld  RJ, Engel  A, Dekkers  PE.  Incidence and causes of colonoscopic perforations: a single-center case series. Endoscopy. 2011;43(3):240-242.
PubMedArticle
159.
Lorenzo-Zúñiga  V, Moreno de Vega  V, Doménech  E, Mañosa  M, Planas  R, Boix  J.  Endoscopist experience as a risk factor for colonoscopic complications. Colorectal Dis. 2010;12(10 online):e273-e277.
PubMedArticle
160.
Macari  M, Nevsky  G, Bonavita  J, Kim  DC, Megibow  AJ, Babb  JS.  CT colonography in senior versus nonsenior patients: extracolonic findings, recommendations for additional imaging, and polyp prevalence. Radiology. 2011;259(3):767-774.
PubMedArticle
161.
Mansmann  U, Crispin  A, Henschel  V,  et al.  Epidemiology and quality control of 245 000 outpatient colonoscopies. Dtsch Arztebl Int. 2008;105(24):434-440.
PubMed
162.
Multicentre Australian Colorectal-neoplasia Screening (MACS) Group.  A comparison of colorectal neoplasia screening tests: a multicentre community-based study of the impact of consumer choice. Med J Aust. 2006;184(11):546-550.
PubMed
163.
Nelson  DB, McQuaid  KR, Bond  JH, Lieberman  DA, Weiss  DG, Johnston  TK.  Procedural success and complications of large-scale screening colonoscopy. Gastrointest Endosc. 2002;55(3):307-314.
PubMedArticle
164.
O’Connor  SD, Pickhardt  PJ, Kim  DH, Oliva  MR, Silverman  SG.  Incidental finding of renal masses at unenhanced CT: prevalence and analysis of features for guiding management. AJR Am J Roentgenol. 2011;197(1):139-145.
PubMedArticle
165.
Parente  F, Boemo  C, Ardizzoia  A,  et al.  Outcomes and cost evaluation of the first two rounds of a colorectal cancer screening program based on immunochemical fecal occult blood test in northern Italy. Endoscopy. 2013;45(1):27-34.
PubMed
166.
Pickhardt  PJ, Boyce  CJ, Kim  DH, Hinshaw  LJ, Taylor  AJ, Winter  TC.  Should small sliding hiatal hernias be reported at CT colonography? AJR Am J Roentgenol. 2011;196(4):W400-W404.
PubMedArticle
167.
Pickhardt  PJ, Kim  DH, Meiners  RJ,  et al.  Colorectal and extracolonic cancers detected at screening CT colonography in 10,286 asymptomatic adults. Radiology. 2010;255(1):83-88.
PubMedArticle
168.
Pickhardt  PJ, Kim  DH, Taylor  AJ, Gopal  DV, Weber  SM, Heise  CP.  Extracolonic tumors of the gastrointestinal tract detected incidentally at screening CT colonography. Dis Colon Rectum. 2007;50(1):56-63.
PubMedArticle
169.
Pickhardt  PJ.  Incidence of colonic perforation at CT colonography: review of existing data and implications for screening of asymptomatic adults. Radiology. 2006;239(2):313-316.
PubMedArticle
170.
Pox  CP, Altenhofen  L, Brenner  H, Theilmeier  A, Von Stillfried  D, Schmiegel  W.  Efficacy of a nationwide screening colonoscopy program for colorectal cancer. Gastroenterology. 2012;142(7):1460-1467.
PubMedArticle
171.
Quallick  MR, Brown  WR.  Rectal perforation during colonoscopic retroflexion: a large, prospective experience in an academic center. Gastrointest Endosc. 2009;69(4):960-963.
PubMedArticle
172.
Rabeneck  L, Paszat  LF, Hilsden  RJ,  et al.  Bleeding and perforation after outpatient colonoscopy and their risk factors in usual clinical practice. Gastroenterology. 2008;135(6):1899-1906.
PubMedArticle
173.
Rathgaber  SW, Wick  TM.  Colonoscopy completion and complication rates in a community gastroenterology practice. Gastrointest Endosc. 2006;64(4):556-562.
PubMedArticle
174.
Rutter  CM, Johnson  E, Miglioretti  DL, Mandelson  MT, Inadomi  J, Buist  DS.  Adverse events after screening and follow-up colonoscopy. Cancer Causes Control. 2012;23(2):289-296.
PubMedArticle
175.
Sagawa  T, Kakizaki  S, Iizuka  H,  et al.  Analysis of colonoscopic perforations at a local clinic and a tertiary hospital. World J Gastroenterol. 2012;18(35):4898-4904.
PubMedArticle
176.
Senore  C, Ederle  A, Fantin  A,  et al.  Acceptability and side-effects of colonoscopy and sigmoidoscopy in a screening setting. J Med Screen. 2011;18(3):128-134.
PubMedArticle
177.
Sieg  A, Hachmoeller-Eisenbach  U, Eisenbach  T.  Prospective evaluation of complications in outpatient GI endoscopy: a survey among German gastroenterologists. Gastrointest Endosc. 2001;53(6):620-627.
PubMedArticle
178.
Singh  H, Penfold  RB, DeCoster  C,  et al.  Colonoscopy and its complications across a Canadian regional health authority. Gastrointest Endosc. 2009;69(3 pt 2):665-671.
PubMedArticle
179.
Sosna  J, Blachar  A, Amitai  M,  et al.  Colonic perforation at CT colonography: assessment of risk in a multicenter large cohort. Radiology. 2006;239(2):457-463.
PubMedArticle
180.
Stock  C, Ihle  P, Sieg  A, Schubert  I, Hoffmeister  M, Brenner  H.  Adverse events requiring hospitalization within 30 days after outpatient screening and nonscreening colonoscopies. Gastrointest Endosc. 2013;77(3):419-429.
PubMedArticle
181.
Strul  H, Kariv  R, Leshno  M,  et al.  The prevalence rate and anatomic location of colorectal adenoma and cancer detected by colonoscopy in average-risk individuals aged 40-80 years. Am J Gastroenterol. 2006;101(2):255-262.
PubMedArticle
182.
Suissa  A, Bentur  OS, Lachter  J,  et al.  Outcome and complications of colonoscopy: a prospective multicenter study in northern Israel. Diagn Ther Endosc. 2012;2012:612542.
PubMedArticle
183.
Tam  MS, Abbas  MA.  Perforation following colorectal endoscopy: what happens beyond the endoscopy suite? Perm J. 2013;17(2):17-21.
PubMedArticle
184.
Veerappan  GR, Ally  MR, Choi  JH, Pak  JS, Maydonovitch  C, Wong  RK.  Extracolonic findings on CT colonography increases yield of colorectal cancer screening. AJR Am J Roentgenol. 2010;195(3):677-686.
PubMedArticle
185.
Viiala  CH, Olynyk  JK.  Outcomes after 10 years of a community-based flexible sigmoidoscopy screening program for colorectal carcinoma. Med J Aust. 2007;187(5):274-277.
PubMed
186.
Wallace  MB, Kemp  JA, Meyer  F,  et al.  Screening for colorectal cancer with flexible sigmoidoscopy by nonphysician endoscopists. Am J Med. 1999;107(3):214-218.
PubMedArticle
187.
Warren  JL, Klabunde  CN, Mariotto  AB,  et al.  Adverse events after outpatient colonoscopy in the Medicare population. Ann Intern Med. 2009;150(12):849-857,W152.
PubMedArticle
188.
Xirasagar  S, Hurley  TG, Sros  L, Hebert  JR.  Quality and safety of screening colonoscopies performed by primary care physicians with standby specialist support. Med Care. 2010;48(8):703-709.
PubMedArticle
189.
Zafar  HM, Harhay  MO, Yang  J, Armstron  K.  Adverse events following computed tomographic colonography compared to optical colonoscopy in the elderly. Prev Med Rep. 2014;1:3-8.
PubMedArticle
190.
Ko  CW, Riffle  S, Michaels  L,  et al.  Serious complications within 30 days of screening and surveillance colonoscopy are uncommon. Clin Gastroenterol Hepatol. 2010;8(2):166-173.
PubMedArticle
191.
Atkin  WS, Hart  A, Edwards  R,  et al.  Uptake, yield of neoplasia, and adverse effects of flexible sigmoidoscopy screening. Gut. 1998;42(4):560-565.
PubMedArticle
192.
Gondal  G, Grotmol  T, Hofstad  B, Bretthauer  M, Eide  TJ, Hoff  G.  The Norwegian Colorectal Cancer Prevention (NORCCAP) screening study: baseline findings and implementations for clinical work-up in age groups 50-64 years. Scand J Gastroenterol. 2003;38(6):635-642.
PubMedArticle
193.
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;338:b1846.
PubMedArticle
194.
Hoff  G, Sauar  J, Vatn  MH,  et al.  Polypectomy of adenomas in the prevention of colorectal cancer: 10 years’ follow-up of the Telemark Polyp Study I: a prospective, controlled population study. Scand J Gastroenterol. 1996;31(10):1006-1010.
PubMedArticle
195.
Kim  DH, Pickhardt  PJ, Hanson  ME, Hinshaw  JL.  CT colonography: performance and program outcome measures in an older screening population. Radiology. 2010;254(2):493-500.
PubMedArticle
196.
Miles  A, Wardle  J, McCaffery  K, Williamson  S, Atkin  W.  The effects of colorectal cancer screening on health attitudes and practices. Cancer Epidemiol Biomarkers Prev. 2003;12(7):651-655.
PubMed
197.
Pickhardt  PJ, Kim  DH, Robbins  JB.  Flat (nonpolypoid) colorectal lesions identified at CT colonography in a US screening population. Acad Radiol. 2010;17(6):784-790.
PubMedArticle
198.
Pickhardt  PJ, Hanson  ME, Vanness  DJ,  et al.  Unsuspected extracolonic findings at screening CT colonography: clinical and economic impact. Radiology. 2008;249(1):151-159.
PubMedArticle
199.
Regula  J, Polkowski  M.  CT colonography versus colonoscopy for the detection of advanced neoplasia. N Engl J Med. 2008;358(1):88-89.
PubMedArticle
200.
Thiis-Evensen  E, Hoff  GS, Sauar  J, Langmark  F, Majak  BM, Vatn  MH.  Population-based surveillance by colonoscopy: effect on the incidence of colorectal cancer: Telemark Polyp Study I. Scand J Gastroenterol. 1999;34(4):414-420.
PubMedArticle
201.
Lord  SJ, Irwig  L, Simes  RJ.  When is measuring sensitivity and specificity sufficient to evaluate a diagnostic test, and when do we need randomized trials? Ann Intern Med. 2006;144(11):850-855.
PubMedArticle
203.
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(7):695-702.
PubMedArticle
204.
Castells  A, Quintero  E.  Programmatic screening for colorectal cancer: the COLONPREV study. Dig Dis Sci. 2015;60(3):672-680.
PubMedArticle
205.
Álvarez  C, Andreu  M, Castells  A,  et al; ColonPrev study investigators.  Relationship of colonoscopy-detected serrated polyps with synchronous advanced neoplasia in average-risk individuals. Gastrointest Endosc. 2013;78(2):333-341.
PubMedArticle
206.
Colonoscopy Versus Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM). ClinicalTrials.gov. https://clinicaltrials.gov/ct2/show/NCT01239082. Accessed May 25, 2016.
207.
Committee to Assess Health Risks from Exposure to Low Levels of Ionizing Radiation, Board on Radiation Effects Research, Division on Earth and Life Studies, National Research Council of the National Academies. Health Risks From Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC: National Academies Press; 2006.
208.
Cardis  E, Vrijheid  M, Blettner  M,  et al.  Risk of cancer after low doses of ionising radiation: retrospective cohort study in 15 countries. BMJ. 2005;331(7508):77.
PubMedArticle
209.
Brenner  DJ, Hall  EJ.  Computed tomography: an increasing source of radiation exposure. N Engl J Med. 2007;357(22):2277-2284.
PubMedArticle
210.
Knudsen  AB, Zauber  AG, Rutter  CM,  et al.  Estimation of benefits, burden, and harms of colorectal cancer screening strategies: modeling study for the US Preventive Services Task Force. JAMA. doi:10.1001/jama.2016.6828.
×