Recommendations on Fecal Immunochemical Testing to Screen for Colorectal Neoplasia: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer

The use of the fecal occult blood test (FOBT) for colorectal cancer (CRC) screening is supported by randomized trials demonstrating effectiveness in cancer prevention and widely recommended by guidelines for this purpose. The fecal immunochemical test (FIT), as a direct measure of human hemoglobin in stool has a number of advantages relative to conventional FOBT and is increasingly used relative to that test. This review summarizes current evidence for FIT in colorectal neoplasia detection and the comparative effectiveness of FIT relative to other commonly used CRC screening modalities. Based on evidence, guidance statements on FIT application were developed and quality metrics for program implementation proposed. The use of the fecal occult blood test (FOBT) for colorectal cancer (CRC) screening is supported by randomized trials demonstrating effectiveness in cancer prevention and widely recommended by guidelines for this purpose. The fecal immunochemical test (FIT), as a direct measure of human hemoglobin in stool has a number of advantages relative to conventional FOBT and is increasingly used relative to that test. This review summarizes current evidence for FIT in colorectal neoplasia detection and the comparative effectiveness of FIT relative to other commonly used CRC screening modalities. Based on evidence, guidance statements on FIT application were developed and quality metrics for program implementation proposed. Stool testing for occult blood has long been recommended for colorectal cancer (CRC) screening in healthy adults.1American Cancer SocietyCancer of the colon and rectum.CA Cancer J Clin. 1980; 30: 208-215Crossref Google Scholar This recommendation is based on randomized controlled trials showing short-term2Hardcastle J.D. Chamberlain J.O. Robinson M.H. et al.Randomised controlled trial of faecal-occult-blood screening for colorectal cancer.Lancet. 1996; 348: 1472-1477Abstract Full Text Full Text PDF PubMed Scopus (2374) Google Scholar, 3Mandel J.S. Bond J.H. Church T.R. et al.Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study.N Engl J Med. 1993; 328: 1365-1371Crossref PubMed Scopus (2844) Google Scholar, 4Kronborg O. Fenger C. Olsen J. et al.Randomised study of screening for colorectal cancer with faecal-occult-blood test.Lancet. 1996; 348: 1467-1471Abstract Full Text Full Text PDF PubMed Scopus (2143) Google Scholar and long-term5Shaukat A. Mongin S.J. Geisser M.S. et al.Long-term mortality after screening for colorectal cancer.N Engl J Med. 2013; 369: 1106-1114Crossref PubMed Scopus (533) Google Scholar, 6Mandel J.S. Church T.R. Bond J.H. et al.The effect of fecal occult-blood screening on the incidence of colorectal cancer.N Engl J Med. 2000; 343: 1603-1607Crossref PubMed Scopus (1201) Google Scholar reductions in CRC incidence and mortality. These studies relied on the guaiac test as an indirect mechanism to detect blood in the stool. Such tests do not examine the stool for human hemoglobin, but rather are predicated on colorimetric detection of peroxidase activity. Specifically, human hemoglobin is a peroxidase catalyst when hydrogen peroxide is added to a guaiac-impregnated card. Unfortunately, many foods contain nonhemoglobin peroxidase activity, which confounds this test. Although guaiac-based CRC screening works, several factors limit its value,7Jaffe R.M. Kasten B. Young D.S. et al.False-negative stool occult blood tests caused by ingestion of ascorbic acid (vitamin C).Ann Intern Med. 1975; 83: 824-826Crossref PubMed Google Scholar as discussed later. Fecal immunochemical tests (FITs) for CRC screening were developed as a direct measure of human hemoglobin in stool, using monoclonal or polyclonal antibodies against the globin moiety of human hemoglobin.8Songster C.L. Barrows G.H. Jarrett D.D. Immunochemical detection of fecal occult blood–the fecal smear punch-disc test: a new non-invasive screening test for colorectal cancer.Cancer. 1980; 45: 1099-1102Crossref PubMed Google Scholar, 9Barrows G.H. Burton R.M. Jarrett D.D. et al.Immunochemical detection of human blood in feces.Am J Clin Pathol. 1978; 69: 342-346Crossref PubMed Scopus (81) Google Scholar Most FITs are qualitative tests that visually indicate when hemoglobin is detected in the sample that is higher than a specific predetermined threshold. A few FITs are quantitative tests, whereby the amount of hemoglobin is measured numerically and then reported as positive if greater than a prespecified threshold. Although long-term, large, programmatic trials with FIT have not been completed yet, prospective data support the effectiveness of FIT as a screening tool, including some evidence that programmatic testing reduces CRC mortality.10Zorzi M. Fedeli U. Schievano E. et al.Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test.Gut. 2015; 64: 784-790Crossref PubMed Scopus (152) Google Scholar, 11Chiang T.H. Chuang S.L. Chen S.L. 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: 1317-1326Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 12Chiu H.M. Chen S.L. Yen A.M. et al.Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program.Cancer. 2015; 121: 3221-3229Crossref PubMed Scopus (127) Google Scholar Although colonoscopy remains central to US-based CRC screening efforts,13Centers for Disease Control and PreventionVital signs: colorectal cancer screening test use–United States, 2012.MMWR Morb Mortal Wkly Rep. 2013; 62: 881-888PubMed Google Scholar to maximize compliance, effective community-based screening requires the availability of multiple screening modalities. FIT now is recognized as an important component of any CRC screening program. This review has multiple purposes. First, to assist health care practitioners in the use of FIT, evidence is summarized about performance characteristics and the comparative effectiveness of FIT. Second, to assist practices or organizations developing FIT-based screening programs, evidence is summarized regarding its application (eg, number of tests and quantitative cut-off values for a positive test). Finally, additional sections of the review address important clinical questions regarding FIT. When possible, recommendations were made using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.14Guyatt G.H. Oxman A.D. Vist G.E. et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926Crossref PubMed Google Scholar The committee relied on 2 previous systematic reviews of the FIT. The first was developed for the US Preventive Services Task Force,15Whitlock E.P. Lin J.S. Liles E. et al.Screening for colorectal cancer: a targeted, updated systematic review for the U.S. Preventive Services Task Force.Ann Intern Med. 2008; 149: 638-658Crossref PubMed Google Scholar and the second addressed the sensitivity of FIT for CRC.16Lee J.K. Liles E.G. Bent S. et al.Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.Ann Intern Med. 2014; 160: 171Crossref PubMed Google Scholar To update this review, a search strategy similar to that used for the more recent review16Lee J.K. Liles E.G. Bent S. et al.Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.Ann Intern Med. 2014; 160: 171Crossref PubMed Google Scholar was used to identify high-quality reports published since August 2013 through September 30, 2015. The updated review used the MEDLINE (Ovid) and Cochrane Database Search strategy as outlined by Lee et al16Lee J.K. Liles E.G. Bent S. et al.Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.Ann Intern Med. 2014; 160: 171Crossref PubMed Google Scholar in their 2014 publication. In addition, 2 authors (D.J.R. and J.K.L.) conducted specific literature searches to identify relevant reports for topics not directly dealing with the test characteristics of FIT and colorectal neoplasia detection. These identified reports then were reviewed and their citations were examined for further works informing the key study questions answered in the document. Although the literature search for the report was broad, the document was designed primarily to address US practice and focused on tests currently approved for use in the United States (Supplementary Table 1). When reporting quantitative hemoglobin measurements, we have followed recommendations by an expert panel and report the results or thresholds as micrograms of hemoglobin per gram of feces.17Fraser C.G. Allison J.E. Halloran S.P. et al.A proposal to standardize reporting units for fecal immunochemical tests for hemoglobin.J Natl Cancer Inst. 2012; 104: 810-814Crossref PubMed Scopus (126) Google Scholar When needed, conversions from reports using nanograms of hemoglobin per milliliter of buffer were converted with the following formula: μg hemoglobin per g feces = (ng hemoglobin per mL × mL buffer)/(mg feces collected). The United States Multi-Society Task Force (USMSTF) is composed of gastroenterologists with focused interest in colorectal cancer representing the American College of Gastroenterology, the American Gastroenterological Association, and the American Society for Gastrointestinal Endoscopy. After the literature review, draft tables and the manuscript were completed and circulated to Task Force members. Guidance statements were developed through consensus obtained through multiple joint teleconferences. Once the final manuscript was complete, it was submitted for review and approval by all 3 gastroenterology societies. The use of GRADE for USMSTF guidance reports has been outlined in detail elsewhere.18Kahi C.J. Boland C.R. Dominitz J.A. et al.Colonoscopy surveillance after colorectal cancer resection: recommendations of the US Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2016; 150: 758-768 e11Abstract Full Text Full Text PDF PubMed Google Scholar GRADE involves a comprehensive literature search and summary (often through meta-analysis), and then a separate review of literature quality and the development of recommendations. The USMSTF uses a modified qualitative approach based on literature review (as described earlier for this report), but without formal meta-analysis. GRADE allows for a separate assessment of the quality of the evidence and strength of recommendation. This approach explicitly recognizes the importance of literature in informing clinical recommendations, but allows latitude because recommendations may be influenced by other factors, such as patient preference and cost. Strong recommendations are those that would be chosen by most informed patients. Weak recommendations are those in which patient values and preferences might play a larger role than the quality of evidence. Within the document, we preface weak recommendations with phrases such as “we suggest,” and strong recommendations with “we recommend.” Several cohort and cross-sectional studies analyzed the single-application test characteristics of FIT for CRC detection with or without a comparative guaiac-based fecal occult blood test (gFOBT), using colonoscopy or at least 2 years of follow-up evaluation as the reference standard19Allison J.E. Sakoda L.C. Levin T.R. et al.Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics.J Natl Cancer Inst. 2007; 99: 1462-1470Crossref PubMed Scopus (307) Google Scholar, 20Allison J.E. Tekawa I.S. Ransom L.J. et al.A comparison of fecal occult-blood tests for colorectal-cancer screening.N Engl J Med. 1996; 334: 155-159Crossref PubMed Scopus (506) Google Scholar, 21Brenner 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: 3049-3054Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar, 22Cheng T.I. Wong J.M. Hong C.F. et al.Colorectal cancer screening in asymptomaic adults: comparison of colonoscopy, sigmoidoscopy and fecal occult blood tests.J Formos Med Assoc. 2002; 101: 685-690PubMed Google Scholar, 23Chiang T.H. Lee Y.C. Tu C.H. et al.Performance of the immunochemical fecal occult blood test in predicting lesions in the lower gastrointestinal tract.CMAJ. 2011; 183: 1474-1481Crossref PubMed Scopus (69) Google Scholar, 24Chiu H.M. Lee Y.C. Tu C.H. et al.Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test.Clin Gastroenterol Hepatol. 2013; 11 (e1-2): 832-838Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 25de Wijkerslooth T.R. Stoop E.M. Bossuyt P.M. et al.Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia.Am J Gastroenterol. 2012; 107: 1570-1578Crossref PubMed Scopus (143) Google Scholar, 26Itoh M. Takahashi K. Nishida H. et al.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: 66-71Crossref PubMed Google Scholar, 27Launoy G.D. Bertrand H.J. 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: 493-496Crossref PubMed Scopus (0) Google Scholar, 28Levi 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: 2415-2424Crossref PubMed Scopus (80) Google Scholar, 29Levi Z. Rozen P. Hazazi R. et al.A quantitative immunochemical fecal occult blood test for colorectal neoplasia.Ann Intern Med. 2007; 146: 244-255Crossref PubMed Google Scholar, 30Morikawa T. Kato J. Yamaji Y. et al.A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population.Gastroenterology. 2005; 129: 422-428Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar, 31Nakama H. Kamijo N. Abdul Fattah A.S. et al.Validity of immunological faecal occult blood screening for colorectal cancer: a follow up study.J Med Screen. 1996; 3: 63-65Crossref PubMed Google Scholar, 32Nakama H. Yamamoto M. Kamijo N. et al.Colonoscopic evaluation of immunochemical fecal occult blood test for detection of colorectal neoplasia.Hepatogastroenterology. 1999; 46: 228-231PubMed Google Scholar, 33Park D.I. Ryu S. Kim Y.H. 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: 2017-2025Crossref PubMed Scopus (243) Google Scholar, 34Nakazato M. Yamano H.-O. Matsushita H.-O. et al.Immunologic fecal occult blood test for colorectal cancer screening.Jpn Med Assoc J. 2006; 49: 203Google Scholar, 35Parra-Blanco A. Gimeno-Garcia A.Z. Quintero E. et al.Diagnostic accuracy of immunochemical versus guaiac faecal occult blood tests for colorectal cancer screening.J Gastroenterol. 2010; 45: 703-712Crossref PubMed Scopus (100) Google Scholar, 36Sohn D.K. Jeong S.Y. Choi H.S. et al.Single immunochemical fecal occult blood test for detection of colorectal neoplasia.Cancer Res Treat. 2005; 37: 20-23Crossref PubMed Google Scholar, 37Imperiale T.F. Ransohoff D.F. Itzkowitz S.H. et al.Multitarget stool DNA testing for colorectal-cancer screening.N Engl J Med. 2014; 370: 1287-1297Crossref PubMed Scopus (870) Google Scholar, 38Hernandez V. Cubiella J. Gonzalez-Mao M.C. et al.Fecal immunochemical test accuracy in average-risk colorectal cancer screening.World J Gastroenterol. 2014; 20: 1038-1047Crossref PubMed Scopus (47) Google Scholar (Table 1). In a meta-analysis of 19 studies in asymptomatic average-risk adults the pooled sensitivity of FIT was 79% (95% confidence interval [CI], 0.69–0.86) for CRC, with a specificity of 94% (95% CI, 0.92–0.95).16Lee J.K. Liles E.G. Bent S. et al.Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.Ann Intern Med. 2014; 160: 171Crossref PubMed Google Scholar Subgroup analysis that was restricted to studies in which only colonoscopy (and not clinical follow-up evaluation) was the reference standard found an overall sensitivity and specificity of 1-time FIT screening for CRC of 77% and 94%, respectively. A very large and recent US study completed after the meta-analysis examined the Food and Drug Administration (FDA)-cleared OC FIT CHEK (Polymedco, Cortland Manor, NY) in 9989 individuals undergoing colonoscopy. The reported sensitivity and specificity for cancer was 74% and 96%, respectively.37Imperiale T.F. Ransohoff D.F. Itzkowitz S.H. et al.Multitarget stool DNA testing for colorectal-cancer screening.N Engl J Med. 2014; 370: 1287-1297Crossref PubMed Scopus (870) Google ScholarTable 1Sensitivity and Specificity of FIT for Colorectal Cancer in an Average-Risk PopulationStudy, yearFIT brandFIT samplesCut-off value, μg/gCohort sizeCRC, nReference standardaEither a colonoscopy (detects CRC and adenomas) or a 2-year longitudinal follow-up evaluation using a cancer registry (only detects CRC) was used for FIT-negative patients.SensitivitySpecificityAllison et al,20Allison J.E. Tekawa I.S. Ransom L.J. et al.A comparison of fecal occult-blood tests for colorectal-cancer screening.N Engl J Med. 1996; 334: 155-159Crossref PubMed Scopus (506) Google Scholar 1996HemeSelectbDiscontinued or not available in the United States.31007493352-year f/u0.690.94Itoh,26Itoh M. Takahashi K. Nishida H. et al.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: 66-71Crossref PubMed Google Scholar 1996OC-HemodiabDiscontinued or not available in the United States.11027,860892-year f/u0.870.95Nakama et al,31Nakama H. Kamijo N. Abdul Fattah A.S. et al.Validity of immunological faecal occult blood screening for colorectal cancer: a follow up study.J Med Screen. 1996; 3: 63-65Crossref PubMed Google Scholar 1996Monohaem1203365122-year f/u0.830.96Nakama et al,32Nakama H. Yamamoto M. Kamijo N. et al.Colonoscopic evaluation of immunochemical fecal occult blood test for detection of colorectal neoplasia.Hepatogastroenterology. 1999; 46: 228-231PubMed Google Scholar 1999Monohaem120461118Colonoscopy0.560.97Cheng et al,22Cheng T.I. Wong J.M. Hong C.F. et al.Colorectal cancer screening in asymptomaic adults: comparison of colonoscopy, sigmoidoscopy and fecal occult blood tests.J Formos Med Assoc. 2002; 101: 685-690PubMed Google Scholar 2002OC-Light110741116Colonoscopy0.880.91Sohn et al,36Sohn D.K. Jeong S.Y. Choi H.S. et al.Single immunochemical fecal occult blood test for detection of colorectal neoplasia.Cancer Res Treat. 2005; 37: 20-23Crossref PubMed Google Scholar 2005OC-HemodiabDiscontinued or not available in the United States.120379412Colonoscopy0.250.99Morikawa et al,30Morikawa T. Kato J. Yamaji Y. et al.A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population.Gastroenterology. 2005; 129: 422-428Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar 2005Magstream HemSp16721,80579Colonoscopy0.660.95Launoy et al,27Launoy G.D. Bertrand H.J. 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: 493-496Crossref PubMed Scopus (0) Google Scholar 2005Magstream HemSp2677421282-year f/u0.860.94Nakazato et al,34Nakazato M. Yamano H.-O. Matsushita H.-O. et al.Immunologic fecal occult blood test for colorectal cancer screening.Jpn Med Assoc J. 2006; 49: 203Google Scholar 2006OC-HemodiabDiscontinued or not available in the United States.216309019Colonoscopy0.530.87Allison et al,19Allison J.E. Sakoda L.C. Levin T.R. et al.Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics.J Natl Cancer Inst. 2007; 99: 1462-1470Crossref PubMed Scopus (307) Google Scholar 2007FlexSure OBT33005356142-year f/u0.860.97Levi et al,29Levi Z. Rozen P. Hazazi R. et al.A quantitative immunochemical fecal occult blood test for colorectal neoplasia.Ann Intern Med. 2007; 146: 244-255Crossref PubMed Google Scholar 2007OC-Micro315803Colonoscopy0.670.83Park et al,33Park D.I. Ryu S. Kim Y.H. 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: 2017-2025Crossref PubMed Scopus (243) Google Scholar 2010OC-Micro12077013Colonoscopy0.770.94Parra-Blanco et al,35Parra-Blanco A. Gimeno-Garcia A.Z. Quintero E. et al.Diagnostic accuracy of immunochemical versus guaiac faecal occult blood tests for colorectal cancer screening.J Gastroenterol. 2010; 45: 703-712Crossref PubMed Scopus (100) Google Scholar 2010OC-Light1101756142-year f/u1.000.93Levi et al,28Levi 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: 2415-2424Crossref PubMed Scopus (80) Google Scholar 2011OC-Micro314120462-year f/u1.000.88Chiang et al,23Chiang T.H. Lee Y.C. Tu C.H. et al.Performance of the immunochemical fecal occult blood test in predicting lesions in the lower gastrointestinal tract.CMAJ. 2011; 183: 1474-1481Crossref PubMed Scopus (69) Google Scholar 2011OC-Light110279628Colonoscopy0.960.87de Wijkerslooth et al,25de Wijkerslooth T.R. Stoop E.M. Bossuyt P.M. et al.Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia.Am J Gastroenterol. 2012; 107: 1570-1578Crossref PubMed Scopus (143) Google Scholar 2012OC-Sensor12012568Colonoscopy0.750.95Chiu et al,24Chiu H.M. Lee Y.C. Tu C.H. et al.Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test.Clin Gastroenterol Hepatol. 2013; 11 (e1-2): 832-838Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar 2013OC-Light110882213Colonoscopy0.850.92Brenner and Tao,21Brenner 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: 3049-3054Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar 2013OC-Sensor16.1223515Colonoscopy0.730.96Brenner and Tao,21Brenner 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: 3049-3054Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar 2013RidascreenbDiscontinued or not available in the United States.124.5223515Colonoscopy0.600.95Imperiale et al,37Imperiale T.F. Ransohoff D.F. Itzkowitz S.H. et al.Multitarget stool DNA testing for colorectal-cancer screening.N Engl J Med. 2014; 370: 1287-1297Crossref PubMed Scopus (870) Google Scholar 2014OC-FIT CHEK120989965Colonoscopy0.740.96Hernandez et al,38Hernandez V. Cubiella J. Gonzalez-Mao M.C. et al.Fecal immunochemical test accuracy in average-risk colorectal cancer screening.World J Gastroenterol. 2014; 20: 1038-1047Crossref PubMed Scopus (47) Google Scholar 2014OC-Sensor1207795Colonoscopy1.000.94f/u, follow-up evaluation.a Either a colonoscopy (detects CRC and adenomas) or a 2-year longitudinal follow-up evaluation using a cancer registry (only detects CRC) was used for FIT-negative patients.b Discontinued or not available in the United States. Open table in a new tab f/u, follow-up evaluation. Few studies compare FIT test characteristics of various brands with one another using cancer as the outcome. In the single comparative effectiveness study21Brenner 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: 3049-3054Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar of 2 FIT brands included in the meta-analysis,16Lee J.K. Liles E.G. Bent S. et al.Accuracy of fecal immunochemical tests for colorectal cancer: systematic review and meta-analysis.Ann Intern Med. 2014; 160: 171Crossref PubMed Google Scholar the FDA approved OC-Sensor (Eiken Chemical Co, Tokyo, Japan) FIT had a higher sensitivity for CRC compared with the RIDASCREEN (R-Biopharm AG, Darmstadt, Germany) FIT (73.3% vs 60.0%, respectively), with similar specificities (95%). Importantly, the sensitivity of quantitative FIT assays can be adjusted by altering the threshold for a positive result. In the prior study, the OC-Sensor cut-off value was 6.1 μg/g vs a RIDASCREEN cut-off value of 24.5 μg/g. Presumably, the sensitivity of the latter test could be improved by reducing the threshold, although this would impact specificity negatively. More recently, investigators using data from the Taiwanese national CRC screening program directly compared 2 FIT tests (OC-Sensor and HM-Jack [Kyowa Medex Co, Tokyo, Japan]) using the same threshold cut-off concentration used programmatically in that country (20 μg hemoglobin [hgb]/g feces). The OC-Sensor test had superior sensitivity for cancer relative to HM-Jack (80% vs 68%; P = .005), although no mortality benefit was observed over the 5-year study period.11Chiang T.H. Chuang S.L. Chen S.L. 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: 1317-1326Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar A separate study compared 2 brands of FIT in a screening program in the Basque Autonomous Region in Spain.39Zubero M.B. Arana-Arri E. Pijoan J.I. et al.Population-based colorectal cancer screening: comparison of two fecal occult blood test.Front Pharmacol. 2014; 4: 175Crossref PubMed Google Scholar Either OC-Sensor (20 μg hgb/g feces) or FOB Gold (Sentinel Diagnostics SpA, Milan, Italy) (20 μg hgb/g feces) was offered (varied by region) to nearly 38,000 individuals. The participation rate was slightly higher with OC-Sensor (61.8% vs 59.1%; P = .008), but there was no significant difference in cancer detection among those who underwent colonoscopy for evaluation of a positive test (5.1% OC-Sensor vs 4.8% FOB Gold). Reports of a single-application, 1-sample FIT showed sensitivity for advanced adenoma (defined as any adenoma ≥10 mm or with villous or high-grade dysplastic features) but varied from 6% to 56% in the screening population21Brenner 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: 3049-3054Abstract Full Text Full Text PDF PubMed Scopus (183) Google Scholar, 24Chiu H.M. Lee Y.C. Tu C.H. et al.Association between early stage colon neoplasms and false-negative results from the fecal immunochemical test.Clin Gastroenterol Hepatol. 2013; 11 (e1-2): 832-838Abstract Full Text Full Text PDF PubMed Scopus (87) Google Scholar, 25de Wijkerslooth T.R. Stoop E.M. Bossuyt P.M. et al.Immunochemical fecal occult blood testing is equally sensitive for proximal and distal advanced neoplasia.Am J Gastroenterol. 2012; 107: 1570-1578Crossref PubMed Scopus (143) Google Scholar, 29Levi Z. Rozen P. Hazazi R. et al.A quantitative immunochemical fecal occult blood test for colorectal neoplasia.Ann Intern Med. 2007; 146: 244-255Crossref PubMed Google Scholar, 30Morikawa T. Kato J. Yamaji Y. et al.A comparison of the immunochemical fecal occult blood test and total colonoscopy in the asymptomatic population.Gastroenterology. 2005; 129: 422-428Abstract Full Text Full Text PDF PubMed Scopus (324) Google Scholar, 33Park D.I. Ryu S. Kim Y.H. 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: 2017-2025Crossref PubMed Scopus (243) Google Scholar, 34Nakazato M. Yamano H.-O. Matsushita H.-O. et al.Immunologic fecal occult blood test for colorectal cancer screening.Jpn Med Assoc J. 2006; 49: 203Google Scholar, 36Sohn D.K. Jeong S.Y. Choi H.S. et al.Single immunochemical fecal occult blood test for detection of colorectal neoplasia.Cancer Res Treat. 2005; 37: 20-23Crossref PubMed Google Scholar, 37Imperiale T.F. Ransohoff D.F. Itzkowitz S.H. et al.Multitarget stool DNA testing for colorectal-cancer screening.N Engl J Med. 2014; 370: 1287-1297Crossref PubMed Scopus (870) Google Scholar, 38Hernandez V. Cubiella J. Gonzalez-Mao M.C. et al.Fecal immunochemical test accuracy in average-risk colorectal cancer screening.World J Gastroenterol. 2014; 20: 1038-1047Crossref PubMed Scopus (47) Google Scholar, 40Graser A. Stieber P. Nagel D. et al.Comparison of