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Figure 1.
PRISMA Flow Diagram
PRISMA Flow Diagram

A search of MEDLINE, EMBASE, the Cochrane Library, and gray literature sources identified 3026 records. After deduplication, 2154 titles and abstracts were screened and 1952 records were rejected or deemed ineligible. The full text of the remaining 202 reports were assessed, and 12 studies met the inclusion criteria and were included in the systematic review.26-37 DARE indicates Database of Abstracts of Reviews of Effects.

Figure 2.
Sensitivity Estimates of Colorectal Cancer and Advanced Neoplasia
Sensitivity Estimates of Colorectal Cancer and Advanced Neoplasia

Forest plots demonstrate a high degree of heterogeneity for sensitivity estimates for (A) colorectal cancer and (B) advanced neoplasia. FN indicates false-negative results; FP, false-positive results; TN, true-negative results; TP, true-positive results.

Table 1.  
Main Characteristics of Studies Included in the Systematic Review and Meta-analysis
Main Characteristics of Studies Included in the Systematic Review and Meta-analysis
Table 2.  
Synopsis of Results From Subgroup Analyses Depending on Cutoff Value, Type of FIT and Number of FIT Samples Used for the Diagnosis of Colorectal Cancer or Advanced Neoplasia
Synopsis of Results From Subgroup Analyses Depending on Cutoff Value, Type of FIT and Number of FIT Samples Used for the Diagnosis of Colorectal Cancer or Advanced Neoplasia
1.
World Health Organization International Agency for Research on Cancer. Colorectal Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed May 8, 2017.
2.
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.PubMedGoogle ScholarCrossref
3.
National Comprehensive Cancer Network. NCCN Guidelines For Colorectal Cancer Screening (Version 2.2016). https://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf. Accessed January 22, 2017.
4.
Amersi  F, Agustin  M, Ko  CY.  Colorectal cancer: epidemiology, risk factors, and health services.  Clin Colon Rectal Surg. 2005;18(3):133-140.PubMedGoogle ScholarCrossref
5.
Bujanda  L, Sarasqueta  C, Zubiaurre  L,  et al; EPICOLON Group.  Low adherence to colonoscopy in the screening of first-degree relatives of patients with colorectal cancer.  Gut. 2007;56(12):1714-1718.PubMedGoogle ScholarCrossref
6.
Dominitz  JA, Eisen  GM, Baron  TH,  et al; Standards of Practice Committee, American Society for Gastrointestinal Endoscopy.  Complications of colonoscopy.  Gastrointest Endosc. 2003;57(4):441-445.Google ScholarCrossref
7.
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.PubMedGoogle ScholarCrossref
8.
Oort  FA, Terhaar Sive Droste  JS, Van Der Hulst  RW,  et al.  Colonoscopy-controlled intra-individual comparisons to screen relevant neoplasia: faecal immunochemical test vs. guaiac-based faecal occult blood test.  Aliment Pharmacol Ther. 2010;31(3):432-439.PubMedGoogle ScholarCrossref
9.
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.PubMedGoogle ScholarCrossref
10.
Lee  JK, Liles  EG, Bent  S, Levin  TR, Corley  DA.  Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.  Ann Intern Med. 2014;160(3):171.PubMedGoogle ScholarCrossref
11.
Jiang  Y, Liu  G, Huang  H,  et al.  Accuracy of immunochemical faecal occult blood test for colorectal cancer: meta-analysis [article in Chinese].  Zhonghua Yu Fang Yi Xue Za Zhi. 2015;49(5):392-398.PubMedGoogle Scholar
12.
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.  Ann Intern Med. 2009;151(4):264-269, W64.Google ScholarCrossref
13.
US Department of Health & Human Services Agency for Healthcare Research and Quality. Systematic Review Data Repository. http://srdr.ahrq.gov/. Accessed August 25, 2016.
14.
Fraser  CG, Allison  JE, Halloran  SP, Young  GP; Expert Working Group on Fecal Immunochemical Tests for Hemoglobin, Colorectal Cancer Screening Committee, World Endoscopy Organization.  A proposal to standardize reporting units for fecal immunochemical tests for hemoglobin.  J Natl Cancer Inst. 2012;104(11):810-814.PubMedGoogle ScholarCrossref
15.
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.PubMedGoogle ScholarCrossref
16.
Gopalakrishna  G, Mustafa  RA, Davenport  C,  et al.  Applying Grading of Recommendations Assessment, Development and Evaluation (GRADE) to diagnostic tests was challenging but doable.  J Clin Epidemiol. 2014;67(7):760-768.PubMedGoogle ScholarCrossref
17.
Schünemann H, Brozek J, Guyatt G, Oxman A, ed; GRADE Working Group. GRADE handbook for grading quality of evidence and strength of recommendations. http://guidelinedevelopment.org/handbook. Updated October 2013. Accessed May 8, 2017.
18.
Brozek  JL, Akl  EA, Alonso-Coello  P,  et al; GRADE Working Group.  Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 1 of 3. an overview of the GRADE approach and grading quality of evidence about interventions.  Allergy. 2009;64(5):669-677.PubMedGoogle ScholarCrossref
19.
Brożek  JL, Akl  EA, Compalati  E,  et al; GRADE Working Group.  Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 3 of 3. the GRADE approach to developing recommendations.  Allergy. 2011;66(5):588-595.PubMedGoogle ScholarCrossref
20.
Brozek  JL, Akl  EA, Jaeschke  R,  et al; GRADE Working Group.  Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 2 of 3. the GRADE approach to grading quality of evidence about diagnostic tests and strategies.  Allergy. 2009;64(8):1109-1116.PubMedGoogle ScholarCrossref
21.
Harbord  RM, Whiting  P.  metandi: meta-analysis of diagnostic accuracy using hierarchical logistic regression.  Stata J. 2009;9(2):211-229.Google Scholar
22.
Dwamena  BA, Sylvester  R, Carlos  RC. midas: meta-analysis of diagnostic accuracy studies. http://fmwww.bc.edu/repec/bocode/m/midas.pdf. Accessed May 8, 2017.
23.
Reitsma  JB, Glas  AS, Rutjes  AW, Scholten  RJ, Bossuyt  PM, Zwinderman  AH.  Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.  J Clin Epidemiol. 2005;58(10):982-990.PubMedGoogle ScholarCrossref
24.
Rutter  CM, Gatsonis  CA.  A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations.  Stat Med. 2001;20(19):2865-2884.PubMedGoogle ScholarCrossref
25.
Arditi  C, Gonvers  JJ, Burnand  B,  et al; EPAGE II Study Group.  Appropriateness of colonoscopy in Europe (EPAGE II). Surveillance after polypectomy and after resection of colorectal cancer.  Endoscopy. 2009;41(3):209-217.PubMedGoogle ScholarCrossref
26.
Gimeno-Garcia  AZ, Carillo-Palau  M, Hernández-Guerra  M,  et al.  Diagnostic yield of the immunochemical fecal occult blood test in asymptomatic first degree relatives of colorectal cancer patients.  Gastroenterology. 2011;140(5)(suppl 1):S-406.Google Scholar
27.
Castro  I, Cubiella  J, Rivera  C,  et al.  Fecal immunochemical test accuracy in familial risk colorectal cancer screening.  Int J Cancer. 2014;134(2):367-375.PubMedGoogle ScholarCrossref
28.
Gimeno-García  AZ, Quintero  E, Nicolás-Pérez  D, Hernández-Guerra  M, Parra-Blanco  A, Jiménez-Sosa  A.  Screening for familial colorectal cancer with a sensitive immunochemical fecal occult blood test: a pilot study.  Eur J Gastroenterol Hepatol. 2009;21(9):1062-1067.PubMedGoogle ScholarCrossref
29.
Hazazi  R, Rozen  P, Leshno  M,  et al.  Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy?  Aliment Pharmacol Ther. 2010;31(4):523-533.PubMedGoogle ScholarCrossref
30.
Hunt  LM, Rooney  PS, Bostock  K, Robinson  MH, Hardcastle  JD, Armitage  NC.  Chemical and immunological testing for faecal occult blood in screening subjects at risk of familial colorectal cancer.  Gut. 1997;40(1):110-112.PubMedGoogle ScholarCrossref
31.
Levi  Z, Rozen  P, Hazazi  R,  et al.  A quantitative immunochemical fecal occult blood test for colorectal neoplasia.  Ann Intern Med. 2007;146(4):244-255.PubMedGoogle ScholarCrossref
32.
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.PubMedGoogle ScholarCrossref
33.
Otero-Estevez  O, De Chiara  L, Rodriguez-Berrocal  FJ,  et al.  Serum sCD26 for colorectal cancer screening in family-risk individuals: comparison with faecal immunochemical test.  Br J Cancer. 2015;112(2):375-381.Google ScholarCrossref
34.
Quintero  E, Carrillo  M, Gimeno-Garcia  AZ,  et al.  Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening.  Gastroenterology. 2014;147(5):1021-1030.e1021; quiz e1016-1027.Google ScholarCrossref
35.
Terhaar sive Droste  JS, van Turenhout  ST, Oort  FA,  et al.  Faecal immunochemical test accuracy in patients referred for surveillance colonoscopy: a multi-centre cohort study.  BMC Gastroenterology. 2012;12:94. doi:10.1186/1471-230X-12-94Google ScholarCrossref
36.
Vleugels  J, Kallenberg  F, De Wijkerslooth  TR,  et al.  Offering colonoscopy to participants with a negative fit and a first degree relative with CRC increases the detection of advanced neoplasia in a screening program.  Gastroenterology. 2015;1:S757.Google ScholarCrossref
37.
Wong  MC, Ching  JY, Chan  VC,  et al.  Factors associated with false-positive and false-negative fecal immunochemical test results for colorectal cancer screening.  Gastrointest Endosc. 2015;81(3):596-607.PubMedGoogle ScholarCrossref
38.
Robertson  DJ, Lee  JK, Boland  CR,  et al.  Recommendations on Fecal Immunochemical Testing to Screen for Colorectal Neoplasia: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer.  Gastroenterology. 2016;(Oct):18.PubMedGoogle Scholar
39.
Higgins  JPT, Green  S, ed.  Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. [updated March 2011] The Cochrane Collaboration; 2011.
40.
Lin  JS, Piper  MA, Perdue  LA,  et al.  Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force.  JAMA. 2016;315(23):2576-2594.PubMedGoogle ScholarCrossref
41.
Carroll  MR, Seaman  HE, Halloran  SP.  Tests and investigations for colorectal cancer screening.  Clin Biochem. 2014;47(10-11):921-939.PubMedGoogle ScholarCrossref
42.
de Wijkerslooth  TR, de Haan  MC, Stoop  EM,  et al.  Reasons for participation and nonparticipation in colorectal cancer screening: a randomized trial of colonoscopy and CT colonography.  Am J Gastroenterol. 2012;107(12):1777-1783.PubMedGoogle ScholarCrossref
43.
Salimzadeh  H, Bishehsari  F, Amani  M,  et al.  Advanced colonic neoplasia in the first degree relatives of colon cancer patients: A colonoscopy-based study.  Int J Cancer. 2016;139(10):2243-2251.PubMedGoogle ScholarCrossref
44.
Berger  BM, Parton  MA, Levin  B.  USPSTF colorectal cancer screening guidelines: an extended look at multi-year interval testing.  Am J Manag Care. 2016;22(2):e77-e81.PubMedGoogle Scholar
45.
Bibbins-Domingo  K, Grossman  DC, Curry  SJ,  et al; US Preventive Services Task Force.  Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.  JAMA. 2016;315(23):2564-2575.PubMedGoogle ScholarCrossref
46.
Bacchus  CM, Dunfield  L, Gorber  SC,  et al.  Recommendations on screening for colorectal cancer in primary care.  CMAJ. 2016;188(5):340-348.Google ScholarCrossref
47.
Deeks  JJ, Altman  DG.  Diagnostic tests 4: likelihood ratios.  BMJ. 2004;329(7458):168-169.PubMedGoogle ScholarCrossref
48.
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.PubMedGoogle ScholarCrossref
49.
Parekh  M, Fendrick  AM, Ladabaum  U.  As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia.  Aliment Pharmacol Ther. 2008;27(8):697-712.PubMedGoogle ScholarCrossref
50.
van Rossum  LG, van Rijn  AF, Verbeek  AL,  et al.  Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis.  Int J Cancer. 2011;128(8):1908-1917.PubMedGoogle ScholarCrossref
51.
Bossuyt  PM, Reitsma  JB, Linnet  K, Moons  KG.  Beyond diagnostic accuracy: the clinical utility of diagnostic tests.  Clin Chem. 2012;58(12):1636-1643.PubMedGoogle ScholarCrossref
Original Investigation
August 2017

Diagnostic Accuracy of Fecal Immunochemical Test in Patients at Increased Risk for Colorectal Cancer: A Meta-analysis

Author Affiliations
  • 1Second Propedeutic Medical Department, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 2Clinical Research and Evidence-Based Medicine Unit, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 3Department of Hygiene and Epidemiology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
  • 4Harris Manchester College, University of Oxford, Oxford, United Kingdom
JAMA Intern Med. 2017;177(8):1110-1118. doi:10.1001/jamainternmed.2017.2309
Key Points

Question  What is the diagnostic accuracy of fecal immunochemical testing (FIT) for screening of colorectal cancer (CRC) or advanced neoplasia in asymptomatic high-risk populations?

Findings  In this meta-analysis, FIT has high overall diagnostic accuracy for CRC and moderate accuracy for advanced neoplasia. Heterogeneity and small sample size limit the precision of the results.

Meaning  Given the safety, simplicity, low cost, and minimal discomfort of FIT, it is a viable alternative screening strategy for patients at increased risk for CRC. This is especially important for those who are averse to colonoscopy.

Abstract

Importance  The potential role of the fecal immunochemical test (FIT) for screening patients at increased risk for colorectal cancer (CRC) has not yet been elucidated.

Objective  To assess the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in asymptomatic patients at above-average risk.

Data Sources  MEDLINE, EMBASE, Cochrane Library, and gray literature sources through August 2016.

Study Selection  Diagnostic studies evaluating the accuracy of FIT for CRC or AN in patients with a personal or familial history of CRC using colonoscopy as the reference standard.

Data Extraction and Synthesis  Two authors (A.K. and P.P.) independently extracted data and evaluated study quality using the Quality Assessment of Diagnostic Accuracy Studies–2 tool, and evaluated the quality of the body of evidence by means of GRADE (Grading of Recommendations Assessment, Development, and Evaluation). Hierarchical models were used to synthesize available evidence.

Main Outcomes and Measures  The primary outcome was the diagnostic performance of FIT for detecting CRC or AN.

Results  We included 12 studies (6204 participants). Seven studies were deemed at high or unclear risk of bias. The average sensitivity of FIT for CRC was 93% (95% CI, 53%-99%), and the average specificity was 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (CI 7.7-13.9) and a negative likelihood ratio (LR−) of 0.08 (95% CI, 0.01-0.75) (GRADE: very low). The average sensitivity of FIT for AN was 48% (95% CI, 39%-57%); and the average specificity was 93% (95% CI, 91%-94%), yielding an LR+ of 6.55 (95% CI, 5.0-8.5) and an LR− of 0.57 (95% CI, 0.48-0.67) (GRADE: very low). Subgroup analyses indicated that FIT cutoff values between 15- and 25-μg/g feces provided the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively). Quantitative and 1-sample FIT showed adequate test performance, but data on other FIT brands and multiple samples were insufficient.

Conclusions and Relevance  The FIT has high overall diagnostic accuracy for CRC but moderate accuracy for AN in patients at above-average personal or familial risk. Heterogeneity and wide confidence intervals limit the trustworthiness of our findings.

Introduction

Quiz Ref IDColorectal cancer (CRC) is the third most common type of cancer in men and the second most common in women worldwide.1 Early detection of CRC through widely applied screening programs has proven to be effective in reduction of cancer-related mortality. Guidelines for average-risk populations support use of several screening modalities, including colonoscopy, fecal occult blood tests or computed tomography colonography. However, recommendations for increased-risk individuals are more aggressive and support only use of colonoscopy. Such a strategy is associated with higher cost, lower adherence, and higher risk for rare, but serious, complications.2-6

It has recently been suggested that fecal immunochemical testing (FIT) could be used for population-based screening owing to its high accuracy and adherence.7-9 Previous systematic reviews and meta-analyses have assessed the performance of FIT in average-risk populations.10,11 However, the potential role of FIT for screening of individuals at increased risk for CRC has not yet been fully elucidated. We conducted a systematic review and meta-analysis to explore the diagnostic accuracy of FIT for CRC or advanced neoplasia (AN) in asymptomatic individuals with a familial or personal history of CRC.

Methods

This review was based on a prespecified protocol registered with PROSPERO 2016 (CRD42016037924) and is reported in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement.12

Study Eligibility Criteria

We included studies that reported the diagnostic accuracy of FIT for CRC or advanced neoplasia (CRC, or adenomas ≥10 mm or with ≥25% villous component and/or high-grade dysplasia) in asymptomatic adults with family history of CRC or personal history of CRC or advanced adenomas and used colonoscopy or follow-up as the reference standard. We excluded studies with symptomatic patients or patients with inflammatory bowel disease, hereditary nonpolyposis colorectal cancer, familial adenomatous polyposis, or studies for which 2 × 2 diagnostic tables could not be inferred.

Identification and Selection of Studies

We conducted a comprehensive search of several electronic databases, including MEDLINE via PubMed, EMBASE via Ovid, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, and the Cochrane Library, without imposing any date or language restrictions. We also searched trial registries and abstracts from relevant scientific meetings, as well as scanned websites of companies manufacturing FITs. Finally, we checked reference lists of primary studies included, relevant systematic reviews and meta-analyses, and pertinent guidelines. The last search was performed in August 2016 (eFigure 1 in the Supplement).

Two authors (A.K. and P.P.) independently reviewed and screened titles and abstracts of articles retrieved and determined final eligibility through examination of full texts. Any disagreement was resolved through discussion or by consulting a third author (A.T.).

Data Extraction and Quality Assessment

Two authors (A.K. and P.P.) independently extracted data from each included study, using Systematic Review Data Repository.13 For studies presenting results for multiple FIT thresholds, we extracted all data to maximize the yield of information. We converted units for FIT cutoff thresholds to micrograms of hemoglobin (Hb) per gram of feces.14 Two authors (A.K. and P.P.) independently evaluated the quality of included studies using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 tool.15 Discrepancies were resolved by consensus.

Assessment of Quality of Body of Evidence

We assessed the quality of evidence by means of Grading of Recommendations Assessment, Development and Evaluation (GRADE).16-20 Two authors (A.K. and P.P.) independently assessed risk of bias, inconsistency, indirectness, imprecision, and publication bias. Overall quality was deemed very low, low, moderate, or high using GRADEpro version 3.6 (GRADEpro GDT).

Data Synthesis

For each study we recalculated the sensitivity and specificity with 95% CIs from the true-positive (TP), false-positive (FP), false-negative (FN), and true-negative (TN) results, using Review Manager 5.3 (Cochrane Community). Statistical analysis was performed with Stata software version 13.0 (Stata Corporation), using metandi and midas modules. We fitted hierarchical logistic regression models when 4 or more studies were available.21-24

In our main analysis, for studies presenting results at multiple FIT thresholds, we used data for the lowest cutoff and the minimum number of samples available. For studies using multiple-sample FIT, positivity was rated based on the highest amount of fecal Hb measured in patient samples. We synthesized data regardless of the FIT cutoff used.

We also conducted a series of prespecified subgroup analyses, based on type of FIT (qualitative or quantitative), number of samples (1, 2, or 3), or FIT cutoff used. We explored the diagnostic accuracy at 3 different FIT thresholds (<15 μg Hb/g, 15 to 25 μg Hb/g, >25 μg Hb/g feces) based on existing practice and to maximize sensitivity for an increased-risk population.

We explored robustness of our findings by means of a series of prespecified sensitivity analyses, excluding studies at high or unclear risk of bias, studies recruiting patients with prior history of CRC or advanced adenomas (potential for spectrum bias),25 or studies that used delayed colonoscopy in patients with FIT-negative results as reference standard (potential for differential reference bias).

Finally, we evaluated the clinical utility of FIT utilizing Fagan nomograms to depict posttest probability in patients at increased risk for CRC and AN.

Results

Our search identified 3026 records (Figure 1). After deduplication, we screened 2154 titles and abstracts and rejected 1952 records as noneligible. We assessed the full text of the remaining 202 reports. Twelve studies met the inclusion criteria and were included in the systematic review.26-37

The main characteristics of included studies are displayed in Table 1. Our main analysis is based on data from 6204 participants. Sample size of studies ranged from 116 to 1041 patients. Mean age ranged from 46.0 to 63.2 years, and percentage of males ranged from 30.2 to 50.6%. Eleven studies were cross-sectional and 1 was a randomized clinical trial.34 Two studies were reported only in abstract form.26,36 Nine studies included only first-degree relatives of CRC patients.26-28,30,32-34,36,37 Three studies included individuals either with a family history of CRC or prior history of CRC or advanced adenomas.29,31,35 Of these, only 2 studies reported results for subgroups.31,35

Eight studies evaluated quantitative FIT (OC-sensor/OC-micro, Eiken Chemical),26,27,29,31,33-36 while 4 studies used qualitative FITs (Hemosure, W.H.P.M. Inc32,37; OC-light, Eiken Chemical28; and HemeSelect, Smith-Kline Diagnostics30). Eight studies used 1-sample FIT,26,28,30,32-34,36,37 2 studies used 2-sample FIT,27,35 and 2 studies used 3-sample FIT.29,31

All studies used colonoscopy as a reference standard. However, in 3 studies, the time interval between FIT and colonoscopy depended on the FIT result, such that colonoscopy was delayed more so in those with a negative FIT.26,34,37

All studies assessed the accuracy of FIT for AN,26-37 but only 7 studies (4790 patients) reported data specifically for CRC.27,29,31-35 Prevalence of AN ranged between 3.2% and 14.5% and between 0.6% and 2.1% for CRC.

Quality Assessment

The methodological quality assessment of the included studies is summarized in eFigures 2 and 3 in the Supplement. Six studies were deemed at high risk of bias,26,28,30,32,34,37 1 study at unclear risk,36 and 5 studies at low risk of bias.27,29,31,33,35

All but 1 study reported use of consecutive or random sampling.30 FIT was used prior to the reference standard in 11 studies, and only 1 study did not provide relevant data.36 All studies used prespecified FIT thresholds. The greatest risk for bias occurred owing to flow and timing. In 3 studies, individuals with positive FIT results underwent immediate colonoscopy, whereas individuals with negative FIT results underwent delayed colonoscopy, introducing potential differential verification bias.26,34,37 Moreover, 3 studies used an unacceptable interval (>3 months) between FIT and reference standard,26,34,37 while 2 studies provided no relevant details.30,36 In the rest of the studies, the interval between FIT and reference standard was less than 1 month in 5 studies27,29,31,33,35 and 2 months in 1 study.28

The greatest concern regarding applicability was due to the FIT and the reference standard used. We deemed all 4 studies employing qualitative FITs28,30,32,37 and all 3 studies using delayed colonoscopy as a reference standard26,34,37 as high risk.

Diagnostic Accuracy

In our main analysis, FIT sensitivity and specificity for diagnosing CRC ranged from 0.25 to 1.00 (median, 0.81) and from 0.87 to 0.95 (median, 0.91), respectively. Respective values for diagnosing AN ranged from 0.29 to 0.83 (median, 0.50) and from 0.85 to 0.98 (median, 0.92). Forest plots demonstrated a high degree of heterogeneity for sensitivity estimates (Figure 2). Pooled estimates of sensitivity and specificity for CRC were 93% (95% CI, 53%-99%) and 91% (95% CI, 89%-92%), yielding a positive likelihood ratio (LR+) of 10.30 (95% CI, 7.7-13.9) and a negative likelihood ratio (LR−) of 0.08 (95% CI, 0.01-0.75). Positive and negative predictive values were 7.7% and 99.9%, respectively. The pooled sensitivity and specificity for AN were 48% (95% CI, 39%-57%) and 93% (95% CI, 91%-94%), yielding an LR+ of 6.5 (95% CI, 5.0-8.5) and an LR− of 0.57 (95% CI, 0.48-0.67). Positive and negative predictive values were 43.8% and 94.0%, respectively. The diagnostic odds ratio (DOR) for diagnosis of CRC and AN was 129 (95% CI, 11-1579) and 11 (95% CI, 8-17), respectively. The area under the ROC (AUC) for diagnosis of CRC and AN was 0.93 (95% CI, 0.90-0.95) and 0.86 (95% CI, 0.83-0.89), respectively (eFigure 4 in the Supplement).

Results for all subgroup analyses are summarized in Table 2.

We assessed the stability of our findings in a series of sensitivity analyses (eTable 1 in the Supplement).

We pooled results from 5 studies that were deemed at low risk of bias. Pooled test characteristic estimates for diagnosing CRC were sensitivity, 97% (95% CI, 62%-100%); specificity, 91% (95% CI, 89%-93%); LR+, 11.20 (95% CI, 8.30-15.10); and LR−, 0.03 (95% CI, 0.00-0.60). Respective values for AN were sensitivity, 44% (95% CI, 34%-53%); specificity, 94% (95% CI, 92%-96%); LR+, 7.70 (95% CI, 5.10-11.70), and LR−, 0.60 (95% CI, 0.51-0.71) (eFigure 5 in the Supplement).

We also conducted a sensitivity analysis including data only from patients with family history of CRC. Pooled test characteristics estimates for diagnosing CRC were sensitivity, 86% (95% CI, 31%-99%); specificity, 91% (95% CI, 89%-93%); LR+, 10.00 (95% CI, 5.80-17.5); and LR−, 0.16 (95% CI, 0.02-1.48). Respective values for AN were sensitivity, 46% (95% CI, 37%-56%); specificity, 93% (95% CI, 90%-95%); LR+, 6.60 (95% CI, 4.90-8.70); and LR−, 0.58 (95% CI, 0.48-0.69).

Moreover, we conducted a sensitivity analysis excluding studies that used delayed colonoscopy as the reference standard. The pooled test characteristics for CRC were sensitivity, 97% (95% CI, 31%-100%); specificity, 91% (95% CI, 89%-93%); LR+, 10.80 (95% CI, 8.00-14.60); and LR−, 0.04 (95% CI, 0.00-2.02). Respective values for AN were sensitivity, 47% (95% CI, 37%-58%); specificity, 93% (95% CI, 91%-95%); LR+, 6.90 (95% CI, 4.90-9.70); and LR−, 0.56 (95% CI, 0.46-0.69).

We explored the robustness of our results in a post hoc sensitivity analysis including only studies in patients with family history of CRC that used quantitative FIT with a cut-off value of less than 25 μg Hb/g feces. Pooled estimates for CRC were sensitivity, 91% (95% CI, 51%-99%); specificity, 92% (95% CI, 88%-94%); LR+, 10.80 (95% CI, 6.60-17.80); and LR−, 0.1 (95% CI, 0.01-0.80). Respective estimates for AN were sensitivity, 47% (95% CI, 39%-55%); specificity, 94% (95% CI, 91%-96%); LR+, 8.10 (95% CI, 5.90-11.20); and LR−, 0.56 (95% CI, 0.49-0.65) (eFigure 6 in the Supplement).

Finally, we could not calculate the pooled estimates in a sensitivity analysis including only studies at low risk of bias in patients with family history of CRC that used immediate colonoscopy due to limited data. In 3 relevant studies, sensitivity for CRC varied from 67% to 100% and specificity from 83% to 95%. Respective values for AN varied from 37% to 56% for sensitivity and 92 to 98% for specificity.

Finally, we explored the clinical utility of FIT for patients at increased risk of CRC by means of Fagan nomogram. Assuming a pretest probability of 0.8% for CRC and 10.2% for AN (median prevalence in 7 and 12 studies included in the present meta-analysis, respectively), a positive result increases the probability of CRC to 8.0% and probability of AN to 42.0%. On the other hand, the posttest probability for CRC or AN following a negative result of FIT is 0% or 6.0% respectively (eFigure 7 in the Supplement).

Quality of Evidence

We assessed the quality of the evidence in our main analysis but also separately for patients with family history or personal history of CRC. Based on GRADE summaries (eTable 2 in the Supplement) we deemed the quality of the evidence to be low or very low.

Discussion

In this systematic review and meta-analysis, we found reasonable diagnostic accuracy of FIT for CRC (AUC, 0.93) and AN (AUC, 0.86) in individuals with either a personal or family history of CRC. The pooled sensitivity was approximately 93% for CRC but much lower for AN (48%). Quiz Ref IDUse of cutoff values between 15 to 25 μg Hb/g feces had the best combination of sensitivity and specificity for the diagnosis of CRC (93% and 94%, respectively), as well as the highest LR+ (15.1) and lowest LR− (0.07). The sensitivity was overall lower in individuals with a family history of CRC compared with a personal history. However, it was restored in a post hoc analysis excluding studies with qualitative FIT or utilizing a threshold of less than 25 μg Hb/g feces. Quiz Ref IDThe type of FIT used and cutoff threshold were the most important contributors to the heterogeneity of results. Subgroup analyses for quantitative FIT and 1-sample FIT showed consistent findings supporting their accuracy; however, we could not draw any conclusions about the diagnostic accuracy of qualitative FIT or use of multiple samples due to insufficient evidence. A sensitivity analysis excluding studies at high or unclear risk of bias verified robustness of our conclusions. However, the validity of our conclusions is undermined by low or very low quality of the body of evidence.

To our knowledge, this is the first systematic review and meta-analysis evaluating the diagnostic accuracy of FIT in individuals at increased risk for CRC. Results were at least as good as from previous systematic reviews focusing οn average-risk individuals.10,11,38 To ensure internal validity of our conclusions, we implemented current guidelines for the conduct and reporting of systematic reviews12,39 and used a prespecified protocol. We undertook a comprehensive search of multiple electronic databases and gray literature sources without imposing any restrictions based on language or publication type. Data extraction and quality assessment were conducted in duplicate. We assessed quality using a meticulous, recently developed tool (QUADAS-2). We synthesized existing data using hierarchical models to account for the correlation between sensitivity and specificity. Finally, we graded the quality of the body of evidence using appropriate methodology (GRADE).

Quiz Ref IDColonoscopy is currently the only recommended screening modality for participants at increased risk of CRC owing to personal or family history.3 However, no study has documented the effectiveness of this policy on CRC incidence or mortality. Colonoscopy is an invasive, expensive procedure with an established risk of complications.40,41 Population-based studies and randomized trials suggest that adherence to use of colonoscopy for screening in average and increased-risk populations is usually suboptimal.42 This undermines the efficacy of screening programs43 and underlines the need for alternative screening modalities that may limit the need for colonoscopy only to those participants with positive results. Several recently published guidelines support the use of FIT for screening of average-risk participants.44,45 The Canadian Task Force on Preventive Health Care excludes colonoscopy as a primary screening test and recommends screening only with FIT, guaiac–based fecal occult blood tests, or flexible sigmoidoscopy.46 Our results are in line with these suggestions and support use of FIT for screening of increased-risk individuals.

High specificity and sensitivity of FIT allow prompt referral of patients with positive results for further diagnostic investigation with colonoscopy, and exclusion of CRC with high certainty in individuals with negative results respectively. FIT LR+ is more than 10 and LR− is less than 0.1, hence having a significant effect on pretest probabilities and providing strong evidence for the presence or absence of CRC, respectively.47 In a population with a prevalence of CRC equal to 0.8%, a negative result decreases the posttest probability to less than 0.1%, whereas a positive result increases the posttest probability to 8.0%, which crosses a conventional threshold of risk to perform colonoscopy. Thus, our results suggest that in increased-risk individuals FIT has high diagnostic accuracy for CRC. On the other hand, our results also show that FIT could diagnose only half of the cases with AN. Nevertheless, all included studies evaluated 1-time application of the test, and results could not be transferred to repeat screening programs. In a pragmatic trial34 assessing the effectiveness of a diagnostic strategy using annual FIT for 3 years for detection of AN vs colonoscopy in asymptomatic patients with a family history of CRC, annual FIT was as good as colonoscopy for AN; however, it missed almost 40% of advanced adenomas. These data support the annual use of FIT in individuals at increased risk for CRC as an alternative screening strategy for patients who refuse to use colonoscopy. Repeat use of FIT and higher compliance to screening schedules48 could potentially counterbalance the superior accuracy of colonoscopy in the diagnosis of AN.

Our results suggest that given FIT safety, simplicity, low cost, and low discomfort, it could be used as an acceptable alternative for screening of individuals at increased risk for CRC.

The latest US Preventive Services Task Force recommendations for colorectal screening support that “the best screening test is the one that gets done,” and that the ultimate goal of screening strategies is maximization of screening uptake to reduce CRC mortality.45

Although our results verify the diagnostic accuracy of FIT for CRC in individuals at increased risk, this body of evidence is limited by a relatively small sample size. It is thus imperative for future studies to include larger and better-defined patient populations. It is also important to establish optimal thresholds, test cutoff values, and number and frequency of FIT samples.10 Our results also should prompt randomized trials to assess the implementation of FIT either alone or in combination with other screening procedures into screening strategies for increased-risk individuals. Finally, the effects on quality of life, morbidity, mortality and overall cost-effectiveness need to be clarified in future studies.49-51

Limitations

Several limitations have to be acknowledged about the evidence and the review itself. Quiz Ref IDDespite the use of an exhaustive and meticulous search strategy, we could only find 12 eligible studies. Most of these were at high or unclear risk of bias due to suboptimal study design.26,28,30,32,34,36,37 Only 3 studies had a mixed population with personal or familial history of CRC,29,31,35 and 2 studies presented results separately based on the patient history.31,35 A post hoc analysis of studies in individuals with family history of CRC using quantitative FIT resulted in similar summary estimates with the main analysis. However, most studies had a small sample size or low prevalence of CRC or AN, limiting the precision of effect estimates. Finally, 3 studies were prone to differential verification bias as they invited participants with negative FIT results to undergo a delayed colonoscopy as the reference standard.26,34,37 Most analyses had high heterogeneity and wide confidence intervals of pooled estimates, hence raising concerns about the reliability of our findings. However, the robustness of our results was verified in a series of subgroup analyses.

Conclusions

FIT has high overall diagnostic accuracy for CRC in increased-risk individuals. The accuracy for advanced neoplasia however is moderate, and so further study of annual FIT to assess increased performance is warranted. Heterogeneity and small sample sizes undermine the quality and validity of these findings. Further research with rigorous diagnostic accuracy studies and randomized clinical trials is warranted to assess the full effectiveness of FIT implementation as a means to promote more individualized and more flexible alternative screening options in patients at higher risk of CRC based on their own values and preferences.

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Article Information

Corresponding Author: Anastasia Katsoula, MD, MSc, Hippokration General Hospital of Thessaloniki 54642, Thessaloniki, Greece (anastkatsoula@gmail.com).

Accepted for Publication: March 8, 2017.

Published Online: June 19, 2017. doi:10.1001/jamainternmed.2017.2309

Author Contributions: Dr Tsapas had full access to all 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: Katsoula, Paschos, Tsapas, Giouleme.

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

Drafting of the manuscript: Katsoula, Paschos, Tsapas.

Critical revision of the manuscript for important intellectual content: All authors.

Statistical analysis: Katsoula, Paschos, Haidich, Tsapas.

Administrative, technical, or material support: Katsoula, Paschos, Tsapas, Giouleme.

Study supervision: Katsoula, Haidich, Tsapas, Giouleme.

Conflict of Interest Disclosures: None reported.

Previous Presentation: This study was presented as an abstract at the 24th United European Gastroenterology Week; October 18, 2016; Vienna, Austria.

References
1.
World Health Organization International Agency for Research on Cancer. Colorectal Cancer: Estimated Incidence, Mortality and Prevalence Worldwide in 2012. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx. Accessed May 8, 2017.
2.
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.PubMedGoogle ScholarCrossref
3.
National Comprehensive Cancer Network. NCCN Guidelines For Colorectal Cancer Screening (Version 2.2016). https://www.nccn.org/professionals/physician_gls/pdf/colorectal_screening.pdf. Accessed January 22, 2017.
4.
Amersi  F, Agustin  M, Ko  CY.  Colorectal cancer: epidemiology, risk factors, and health services.  Clin Colon Rectal Surg. 2005;18(3):133-140.PubMedGoogle ScholarCrossref
5.
Bujanda  L, Sarasqueta  C, Zubiaurre  L,  et al; EPICOLON Group.  Low adherence to colonoscopy in the screening of first-degree relatives of patients with colorectal cancer.  Gut. 2007;56(12):1714-1718.PubMedGoogle ScholarCrossref
6.
Dominitz  JA, Eisen  GM, Baron  TH,  et al; Standards of Practice Committee, American Society for Gastrointestinal Endoscopy.  Complications of colonoscopy.  Gastrointest Endosc. 2003;57(4):441-445.Google ScholarCrossref
7.
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.PubMedGoogle ScholarCrossref
8.
Oort  FA, Terhaar Sive Droste  JS, Van Der Hulst  RW,  et al.  Colonoscopy-controlled intra-individual comparisons to screen relevant neoplasia: faecal immunochemical test vs. guaiac-based faecal occult blood test.  Aliment Pharmacol Ther. 2010;31(3):432-439.PubMedGoogle ScholarCrossref
9.
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.PubMedGoogle ScholarCrossref
10.
Lee  JK, Liles  EG, Bent  S, Levin  TR, Corley  DA.  Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.  Ann Intern Med. 2014;160(3):171.PubMedGoogle ScholarCrossref
11.
Jiang  Y, Liu  G, Huang  H,  et al.  Accuracy of immunochemical faecal occult blood test for colorectal cancer: meta-analysis [article in Chinese].  Zhonghua Yu Fang Yi Xue Za Zhi. 2015;49(5):392-398.PubMedGoogle Scholar
12.
Moher  D, Liberati  A, Tetzlaff  J, Altman  DG; PRISMA Group.  Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.  Ann Intern Med. 2009;151(4):264-269, W64.Google ScholarCrossref
13.
US Department of Health & Human Services Agency for Healthcare Research and Quality. Systematic Review Data Repository. http://srdr.ahrq.gov/. Accessed August 25, 2016.
14.
Fraser  CG, Allison  JE, Halloran  SP, Young  GP; Expert Working Group on Fecal Immunochemical Tests for Hemoglobin, Colorectal Cancer Screening Committee, World Endoscopy Organization.  A proposal to standardize reporting units for fecal immunochemical tests for hemoglobin.  J Natl Cancer Inst. 2012;104(11):810-814.PubMedGoogle ScholarCrossref
15.
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.PubMedGoogle ScholarCrossref
16.
Gopalakrishna  G, Mustafa  RA, Davenport  C,  et al.  Applying Grading of Recommendations Assessment, Development and Evaluation (GRADE) to diagnostic tests was challenging but doable.  J Clin Epidemiol. 2014;67(7):760-768.PubMedGoogle ScholarCrossref
17.
Schünemann H, Brozek J, Guyatt G, Oxman A, ed; GRADE Working Group. GRADE handbook for grading quality of evidence and strength of recommendations. http://guidelinedevelopment.org/handbook. Updated October 2013. Accessed May 8, 2017.
18.
Brozek  JL, Akl  EA, Alonso-Coello  P,  et al; GRADE Working Group.  Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 1 of 3. an overview of the GRADE approach and grading quality of evidence about interventions.  Allergy. 2009;64(5):669-677.PubMedGoogle ScholarCrossref
19.
Brożek  JL, Akl  EA, Compalati  E,  et al; GRADE Working Group.  Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 3 of 3. the GRADE approach to developing recommendations.  Allergy. 2011;66(5):588-595.PubMedGoogle ScholarCrossref
20.
Brozek  JL, Akl  EA, Jaeschke  R,  et al; GRADE Working Group.  Grading quality of evidence and strength of recommendations in clinical practice guidelines: part 2 of 3. the GRADE approach to grading quality of evidence about diagnostic tests and strategies.  Allergy. 2009;64(8):1109-1116.PubMedGoogle ScholarCrossref
21.
Harbord  RM, Whiting  P.  metandi: meta-analysis of diagnostic accuracy using hierarchical logistic regression.  Stata J. 2009;9(2):211-229.Google Scholar
22.
Dwamena  BA, Sylvester  R, Carlos  RC. midas: meta-analysis of diagnostic accuracy studies. http://fmwww.bc.edu/repec/bocode/m/midas.pdf. Accessed May 8, 2017.
23.
Reitsma  JB, Glas  AS, Rutjes  AW, Scholten  RJ, Bossuyt  PM, Zwinderman  AH.  Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews.  J Clin Epidemiol. 2005;58(10):982-990.PubMedGoogle ScholarCrossref
24.
Rutter  CM, Gatsonis  CA.  A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations.  Stat Med. 2001;20(19):2865-2884.PubMedGoogle ScholarCrossref
25.
Arditi  C, Gonvers  JJ, Burnand  B,  et al; EPAGE II Study Group.  Appropriateness of colonoscopy in Europe (EPAGE II). Surveillance after polypectomy and after resection of colorectal cancer.  Endoscopy. 2009;41(3):209-217.PubMedGoogle ScholarCrossref
26.
Gimeno-Garcia  AZ, Carillo-Palau  M, Hernández-Guerra  M,  et al.  Diagnostic yield of the immunochemical fecal occult blood test in asymptomatic first degree relatives of colorectal cancer patients.  Gastroenterology. 2011;140(5)(suppl 1):S-406.Google Scholar
27.
Castro  I, Cubiella  J, Rivera  C,  et al.  Fecal immunochemical test accuracy in familial risk colorectal cancer screening.  Int J Cancer. 2014;134(2):367-375.PubMedGoogle ScholarCrossref
28.
Gimeno-García  AZ, Quintero  E, Nicolás-Pérez  D, Hernández-Guerra  M, Parra-Blanco  A, Jiménez-Sosa  A.  Screening for familial colorectal cancer with a sensitive immunochemical fecal occult blood test: a pilot study.  Eur J Gastroenterol Hepatol. 2009;21(9):1062-1067.PubMedGoogle ScholarCrossref
29.
Hazazi  R, Rozen  P, Leshno  M,  et al.  Can patients at high risk for significant colorectal neoplasms and having normal quantitative faecal occult blood test postpone elective colonoscopy?  Aliment Pharmacol Ther. 2010;31(4):523-533.PubMedGoogle ScholarCrossref
30.
Hunt  LM, Rooney  PS, Bostock  K, Robinson  MH, Hardcastle  JD, Armitage  NC.  Chemical and immunological testing for faecal occult blood in screening subjects at risk of familial colorectal cancer.  Gut. 1997;40(1):110-112.PubMedGoogle ScholarCrossref
31.
Levi  Z, Rozen  P, Hazazi  R,  et al.  A quantitative immunochemical fecal occult blood test for colorectal neoplasia.  Ann Intern Med. 2007;146(4):244-255.PubMedGoogle ScholarCrossref
32.
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.PubMedGoogle ScholarCrossref
33.
Otero-Estevez  O, De Chiara  L, Rodriguez-Berrocal  FJ,  et al.  Serum sCD26 for colorectal cancer screening in family-risk individuals: comparison with faecal immunochemical test.  Br J Cancer. 2015;112(2):375-381.Google ScholarCrossref
34.
Quintero  E, Carrillo  M, Gimeno-Garcia  AZ,  et al.  Equivalency of fecal immunochemical tests and colonoscopy in familial colorectal cancer screening.  Gastroenterology. 2014;147(5):1021-1030.e1021; quiz e1016-1027.Google ScholarCrossref
35.
Terhaar sive Droste  JS, van Turenhout  ST, Oort  FA,  et al.  Faecal immunochemical test accuracy in patients referred for surveillance colonoscopy: a multi-centre cohort study.  BMC Gastroenterology. 2012;12:94. doi:10.1186/1471-230X-12-94Google ScholarCrossref
36.
Vleugels  J, Kallenberg  F, De Wijkerslooth  TR,  et al.  Offering colonoscopy to participants with a negative fit and a first degree relative with CRC increases the detection of advanced neoplasia in a screening program.  Gastroenterology. 2015;1:S757.Google ScholarCrossref
37.
Wong  MC, Ching  JY, Chan  VC,  et al.  Factors associated with false-positive and false-negative fecal immunochemical test results for colorectal cancer screening.  Gastrointest Endosc. 2015;81(3):596-607.PubMedGoogle ScholarCrossref
38.
Robertson  DJ, Lee  JK, Boland  CR,  et al.  Recommendations on Fecal Immunochemical Testing to Screen for Colorectal Neoplasia: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer.  Gastroenterology. 2016;(Oct):18.PubMedGoogle Scholar
39.
Higgins  JPT, Green  S, ed.  Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0. [updated March 2011] The Cochrane Collaboration; 2011.
40.
Lin  JS, Piper  MA, Perdue  LA,  et al.  Screening for colorectal cancer: updated evidence report and systematic review for the US Preventive Services Task Force.  JAMA. 2016;315(23):2576-2594.PubMedGoogle ScholarCrossref
41.
Carroll  MR, Seaman  HE, Halloran  SP.  Tests and investigations for colorectal cancer screening.  Clin Biochem. 2014;47(10-11):921-939.PubMedGoogle ScholarCrossref
42.
de Wijkerslooth  TR, de Haan  MC, Stoop  EM,  et al.  Reasons for participation and nonparticipation in colorectal cancer screening: a randomized trial of colonoscopy and CT colonography.  Am J Gastroenterol. 2012;107(12):1777-1783.PubMedGoogle ScholarCrossref
43.
Salimzadeh  H, Bishehsari  F, Amani  M,  et al.  Advanced colonic neoplasia in the first degree relatives of colon cancer patients: A colonoscopy-based study.  Int J Cancer. 2016;139(10):2243-2251.PubMedGoogle ScholarCrossref
44.
Berger  BM, Parton  MA, Levin  B.  USPSTF colorectal cancer screening guidelines: an extended look at multi-year interval testing.  Am J Manag Care. 2016;22(2):e77-e81.PubMedGoogle Scholar
45.
Bibbins-Domingo  K, Grossman  DC, Curry  SJ,  et al; US Preventive Services Task Force.  Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement.  JAMA. 2016;315(23):2564-2575.PubMedGoogle ScholarCrossref
46.
Bacchus  CM, Dunfield  L, Gorber  SC,  et al.  Recommendations on screening for colorectal cancer in primary care.  CMAJ. 2016;188(5):340-348.Google ScholarCrossref
47.
Deeks  JJ, Altman  DG.  Diagnostic tests 4: likelihood ratios.  BMJ. 2004;329(7458):168-169.PubMedGoogle ScholarCrossref
48.
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.PubMedGoogle ScholarCrossref
49.
Parekh  M, Fendrick  AM, Ladabaum  U.  As tests evolve and costs of cancer care rise: reappraising stool-based screening for colorectal neoplasia.  Aliment Pharmacol Ther. 2008;27(8):697-712.PubMedGoogle ScholarCrossref
50.
van Rossum  LG, van Rijn  AF, Verbeek  AL,  et al.  Colorectal cancer screening comparing no screening, immunochemical and guaiac fecal occult blood tests: a cost-effectiveness analysis.  Int J Cancer. 2011;128(8):1908-1917.PubMedGoogle ScholarCrossref
51.
Bossuyt  PM, Reitsma  JB, Linnet  K, Moons  KG.  Beyond diagnostic accuracy: the clinical utility of diagnostic tests.  Clin Chem. 2012;58(12):1636-1643.PubMedGoogle ScholarCrossref
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