Gastroenterology
Volume 129, Issue 2 , Pages 745-748, August 2005

Colon Cancer Screening Guidelines 2005: The Fecal Occult Blood Test Option Has Become a Better FIT

  • James E. Allison

      Affiliations

    • Corresponding Author InformationAddress requests for reprints to: James E. Allison, MD, Clinical Professor of Medicine UCSF, Division of Gastroenterology, San Francisco General Hospital, 1001 Potrero Avenue, NH-3D, Oakland, California 94110. fax: (415) 641-0745.

Article Outline

 

In this issue of Gastroenterology Morikawa et al1 present important data on the performance characteristics of a new fecal immunochemical test (FIT), Magstream 1000/Hem SP (Fujirebio Inc, Tokyo, Japan), in a large, average risk Japanese population. They used the Magstream 1000/Hem SP automated system (Fujirebio) and determined sensitivity, specificity, and positive predictive value by performing colonoscopy on all patients regardless of FIT result. The overall positivity rate was 5.6%. The sensitivity of the FIT for colon cancer was 66% and 20% for polyps > 1 cm. A 66% sensitivity for cancer is a marked improvement over the colonoscopy confirmed 13%–39% sensitivity reported for the most commonly used guaiac test (GT) Hemoccult II (Beckman Coulter, Inc, Fullerton, CA).2, 3 It is remarkably similar to that reported for the FIT HemeSelect (69%).4 The FIT, FlexSure OBT, has been shown to have a better sensitivity than Magstream for left-sided cancers (82%) and left-sided polyps > 1 cm (25%) when patients with both positive and negative results were sigmoidoscoped.5

The problems with the study design are dealt with well in the Discussion section of the manuscript. They are all offset by the valuable information this study offers on the performance characteristics (verified by a “gold standard” endoscopic exam) of another FIT. Before FIT development only GT were available. GT detect any peroxidase activity in the feces. Heme either as intact hemoglobin or free heme has peroxidase-like activity therefore, in the presence of heme and a developer (hydrogen peroxide), guaiac acid is oxidized producing a blue color. Heme is present in red meat, and peroxidase activity is present in fresh fruits and vegetables such as radishes, turnips, and broccoli. These foods, therefore, have the potential to produce false-positive results. Although there are several available guaiac tests only 2, Hemoccult II and Hemoccult Sensa, have been extensively evaluated in large screening populations. Accurate interpretation of results for GT requires training and supervision especially when interpreting borderline results.6, 7, 8 Results are affected by vitamin C, which inhibits the guaiac reaction.9 The person screened is required to be on a red meat and peroxidase-containing, food-free diet and to collect the stool sample in the dry state sampling the feces with a wooden stick. All these requirements limit patient acceptance and make interpretation of test results questionable except in well-run laboratories. In a group of motivated volunteers in an Australian population where red meat consumption is relatively high, a restrictive diet reduced participation by 13%.10

The fecal immunochemical tests (FIT) address many of the weaknesses of the GT. They have superior sensitivity and specificity.4, 5 The application sensitivities for cancer are good (66%–82%) but for polyps > 1 cm they are more modest; however, the use of a program of fecal occult blood test (FOBT) screening (in which screening is performed yearly or every other year) may result in a cumulative sensitivity of the program that is competitive with a program of a more sensitive test performed less frequently. Specifically, a combined program of FOBT plus sigmoidoscopy may be as effective as or more effective than a program of colonoscopy screening every 10 years11 because improved FOBT tests such as FIT are more sensitive than the widely used Hemoccult II. The suggestion of some experts that FOBT screening should be seriously considered by physicians, patients, and policy makers12 should now make the case for FOBT even stronger. The FITs efficacy in decreasing colon cancer mortality and incidence has not been studied in randomized controlled trials but, Fletcher has pointed out that if new screening tests are truly more accurate than GT (Hemoccult II), their effectiveness need not be confirmed by randomized controlled trials because Hemoccult II’s ability to save lives from colorectal cancer has already been shown.13

FITs use antibodies specific for human globin and are, unlike the GT, specific for colorectal bleeding and not affected by diet or medications. Some can be developed by automated developers and readers. This innovation allows for managing large numbers of tests in a standardized manner with excellent quality assurance. There is evidence that FIT use improves patient participation in screening for colorectal cancer.14 Some new technology FITs are able to quantify fecal hemoglobin allowing for adjustment of sensitivity, specificity, and positivity rates when screening for colorectal neoplasia.15 The developing instrument for some FITs has the ability to read a bar code on the test. This ensures accurate identification of the person screened and allows for a print out of the result, as well as a reminder print- out for future compliance. When these innovations have been perfected and tested in large asymptomatic populations, government agencies or individual health plans will be able to decide what positivity rate their budget and manpower resources can accommodate and still have good sensitivity and specificity for advanced neoplasms in an annual screening program. Australia has initiated a colon cancer screening program using InSure and Magstream 1000/ Hem SP and the United Kingdom and Canada are considering the use of FITs in their screening programs. Japan has been using FITs successfully for years.

The new and improved FIT choices are now available and reimbursable by CMS at $22 per test (includes completed test card with 2 samples and analysis). In 2004, CMS concluded that adequate evidence existed to determine that the immunoassay fecal occult blood test (FIT) is an appropriate and effective colorectal cancer screening test for detecting fecal occult blood in Medicare beneficiaries aged ≥50 years. The CMS reimbursement decision has lead to the appearance of several FITs approved by the FDA for marketing in the United States which, in addition to InSure (Enterix USA, Inc, NJ), include Instant-View (Alpha Scientific Designs, San Diego, CA), immoCARE (Care Health Technologies, Ltd, Waterbury, CT), MonoHaem (Chemicon International, Inc, Temecula, CA), and Clearview Ultra-FOB (Inverness Medical, Newton, MA). FlexSure OBT (Beckman Coulter, Palo Alto, CA) will soon reappear as Hemoccult-ICT (Beckman Coulter Inc, Primary Care Diagnostics, Los Angeles, CA). Magstream 1000/Hem SP (Fujirebio Inc, Tokyo, Japan) is marketed in Australia and Europe (Bayer Diagnostics, Tarrytown, NY) as Bayer Detect and is also likely to be marketed in the US. These tests differ in the methods used for stool handling and sampling, how (automated or laboratory technician) and where (office or laboratory) the tests are developed. Only FlexSure OBT, HemeSelect, InSure, and now MagStream1000/Hem SP have been evaluated in large numbers (thousands) of average risk patients with results published in US peer-reviewed journals.

Despite all the data cited above, clinicians, patients, and the lay press may still dismiss choices other than colonoscopy for colon cancer screening because of statements that other tests may miss 25%–65% of advanced neoplasms. I would answer as follows:

1.All the most recent screening guidelines recommend a menu of screening options that include FOBT.16, 17, 18 Furthermore, and very importantly, the United States Preventive Services Task Force (USPSTF) in 2002 concluded that the 2 most effective screening strategies were annual fecal occult blood testing and sigmoidoscopy every 5 years or colonoscopy every 10 years. In other words, a strategy using the currently available less-sensitive version of FOBT (HOC II) is already competitive, at the individual patient level, compared with a program of colonoscopy screening, thus any improvement in application sensitivity would correspondingly improve such a program.11 The Task Force found that 5 multiple-strategy analyses did not uniformly find that colonoscopic screening was the most effective or cost effective strategy. Similar conclusions were reached by members of the Institute of Medicine and the National Research Council in a workshop conference held on the Economic Models of Colorectal Cancer Screening in Average-Risk Adults.19

2.Colonoscopy is only one of several good tests available for colon cancer screening, and we have been cautioned about assuming a screening colonoscopy is as good as gold.20

3.Advanced colonic neoplasms consist of a range of lesions (from large tubular adenomas to early adenocarcinoma) that vary widely in terms of the risk of progression to fatal cancer. Large polyps (>1 cm) become colorectal cancers at a rate of roughly 1% per year.21 A large polyp, left in situ, has a cumulative risk of malignancy at 20 years of only 24%.22 The development of invasive cancer from a small (<10 mm) adenoma is extremely unlikely in less than 5 years.23 Since most polyps, even the “advanced” ones, do not directly lead to death from colon cancer, the most important value of one test over another is the incremental benefit of mortality reduction that test confers to the patient being screened. If screening tests other than colonoscopy are used as directed, that incremental benefit of colonoscopy is small.

4.A screening colonoscopy doesn’t immunize a patient from getting or dying from colon cancer for 10 years. Colonoscopy has a significant miss rate of its own,24, 25, 26, 27 and a program strategy of FIT might be able to uncover both the colonoscopy misses and the fast-growing lesions.28 Flat or depressed adenomas may progress more rapidly than polypoid adenomas to cancer, and flat adenomas and cancers are easy to miss during conventional endoscopy; their true incidence in the West has yet to be determined.29 As the Task Force points out, if cancers most likely to be fatal are those which develop and grow rapidly, there is an advantage to a screening program that allows multiple chances to detect an existing lesion rather than once every 10 years as currently recommended for colonoscopy screening.11, 12, 19

5.Evidence suggests the manpower necessary to provide a skilled colonoscopic examination for all eligible US citizens is inadequate.30, 31 Unqualified examiners could absorb the overflow and the increased inaccuracy and complications could undo the small incremental benefit that the test offers.32 The millions who undergo screening for no apparent gain are subject to harms that could cumulatively outweigh the benefits to the smaller group (those found to have advanced neoplasms) especially if the added benefit is not very great compared with other screening options.32, 33 The serious complication rate in the VA study where the endoscopists were all very skilled was 10/3000 or 1 in 300 including a cerebrovascular accident (CVA) and a myocardial infarction (MI).34

6.The costs of population screening with colonoscopy are particularly worrisome at a time when our federal deficit is projected to hit a record $477 billion, and there are other worthy causes (prescription drug benefits, screening for breast cancer, childhood vaccinations, etc.) competing for health dollars. In the United Kingdom, policy-makers have written that population screening by colonoscopy is a nonstarter for the foreseeable future.35 The UK has neither the manpower nor the necessary facilities to undertake such screening and their experts estimate the complication rate arising from screening 171,000 people aged 60 years using colonoscopy would be unacceptable (over 500 cases of severe hemorrhages, over 150 perforations, and 50 deaths each year). If history is any lesson, the current reimbursement for colonoscopy is unlikely to remain stable or increase. For flexible sigmoidoscopy the rate became too low to justify the required equipment, staff time, and dedicated space.36, 37

7.The early promise of a fecal DNA test for screening38 has not been realized in large multicenter trials where this test was compared with the GTs, Hemoccult II, and Hemoccult Sensa.2, 3, 39

It is not realistic to believe any colorectal cancer screening test will ever detect all advanced neoplasms. As Fletcher has pointed out, clinicians should be prepared to miss some cancers because many other factors such as complications, inconvenience, discomfort, cost effectiveness, and the workforce needed to perform procedures are also in the balance when deciding which screening policies make the most sense.40 The best screening test is the one that gets done.41 The choice of screening tests should be suited to the screening situation. All the recommendations for a FOBT option in colon cancer screening guidelines were made on the basis of findings from randomized controlled trials using GT. If, as it appears, the FIT has better performance characteristics than the GT, that is compelling evidence for recommending its use as the FOBT of choice in colon cancer screening programs.42 Screening programs involving new FOBTs deserve serious consideration as a part of our armamentarium of tests for CRC screening.

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References 

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 Dr. Allison is on the Scientific Advisory Board of Enterix Corportation.

PII: S0016-5085(05)01196-0

doi:10.1053/j.gastro.2005.06.034

Refers to article:

  • A Comparison of the Immunochemical Fecal Occult Blood Test and Total Colonoscopy in the Asymptomatic Population

    Tamiya Morikawa, Jun Kato, Yutaka Yamaji, Ryoichi Wada, Toru Mitsushima, Yasushi Shiratori
    Gastroenterology August 2005 (Vol. 129, Issue 2, Pages 422-428)

Gastroenterology
Volume 129, Issue 2 , Pages 745-748, August 2005