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Gut. 2007 October; 56(10): 1343–1344.
PMCID: PMC2000262

What is the role of iFOBT in screening for colorectal cancer?

Short abstract

Policy makers will need to consider if it has one, not only as an adjunct to gFOBT screening, but also as a primary screening test

Keywords: colorectal cancer, screening, faecal occult blood test

Screening for colorectal cancer (CRC) using gFOBT (guaiac based faecal occult blood test) has been shown in randomised controlled trials (RCTs) to reduce CRC mortality.1,2,3 gFOBT testing is endorsed as an option for CRC screening in the United States4,5,6,7 and is being implemented in the United Kingdom. People with a positive gFOBT receive colonoscopy to detect early cancers and advanced adenomas that, if untreated, might cause CRC mortality. Because gFOBT has a high rate of false positive results, however, gFOBT screening can incur substantial cost and use of colonoscopy resources. A method that could determine which people with a positive gFOBT have false positive results—and do not need colonoscopy—would make gFOBT screening more practical.

A study in this issue of Gut8 Fraser et al(see p 1415) shows that doing iFOBT (human haemoglobin immunochemical based FOBT) in people with a positive gFOBT will detect almost all clinically important lesions in gFOBT positive individuals, while reducing false positive results and the need for colonoscopy. In this study, both iFOBT and colonoscopy were done in those with a positive gFOBT, defined as one to four positive gFOBT ovals (people with five or six positive ovals were automatically referred for colonoscopy). The sensitivity of iFOBT among people with positive gFOBT was 95.9%, while specificity was 59.2%, resulting in a 30% reduction of colonoscopy use. The mechanism by which iFOBT achieves higher specificity than gFOBT presumably is elimination of false positives that occur in guaiac based testing from sources other than human haemoglobin, like diet.

Learning that iFOBT may have a role in a programme of gFOBT screening is practical and important, but it raises a larger question that will need to be sorted out over time. Should iFOBT replace gFOBT as the primary test in a programme of FOBT screening? The authors note that the unit cost for iFOBT is higher than for gFOBT, but that is only one consideration.8 Others include the increased benefit that might be achieved, additional costs (including false positives), and the public's willingness to pay for greater benefit.

The potential usefulness of iFOBT vs gFOBT screening depends largely on the “absolute sensitivity” of each FOBT, a question not addressed in this study that assessed iFOBT sensitivity only among those who already had a positive gFOBT. Used in this way, iFOBT can never do better than gFOBT.

What is the absolute sensitivity for each FOBT? Obtaining absolute sensitivity for any FOBT is logistically difficult, requiring administration of both the FOBT and a “gold standard” exam (like colonoscopy). In asymptomatic individuals the prevalence of CRC is so low, roughly 1–3 per 1000, that thousands of people need to be studied. In one report, gFOBT sensitivity for CRC was about 30%9; in another it was 13%.10 The different results might be explained by use of centralised FOBT processing in the former study (as is also done in the current study, in RCTs, and in the UK screening programme being implemented), while in the latter study processing was done in each physician's office.

While these are low values for absolute sensitivity of gFOBT, they are high enough, as shown in RCTs, to reduce CRC mortality by 33% in a US1 trial and by about 16% in two European trials.2,3 Some mortality reduction may be achieved by repeated application of FOBT in a programme of screening. gFOBT screening is considered not only an “option” for CRC screening, but when combined with sigmoidoscopy, it may be competitive, in terms of effectiveness, with a programme of colonoscopy screening.11,12 This seeming paradox—that a less sensitive test like FOBT might be as effective or more effective than a “gold standard” test like colonoscopy—can be explained by considering how a “programme” of screening works. If a test with lower sensitivity at any one application is applied repeatedly over time in a programme of screening, it may result in a higher “programme” sensitivity than when a more sensitive test (like colonoscopy) is applied less frequently, because a more frequently applied test can detect fast growing CRC that would be missed by a less frequently applied test.11,12,13

If gFOBT is not simply “acceptable” but perhaps is even competitive with colonoscopy in some settings, then what would be the impact of a better FOBT? The absolute sensitivity of iFOBT in recent studies has been shown to be roughly 60% for CRC,14,15,16,17 much higher than for gFOBT. Even without new RCT data to assess CRC mortality reduction, policy decisions may be based on data about the sensitivity and specificity of newer tests, existing RCT results, and modelling.7 Policy makers will need to consider whether iFOBT has a role not only as an adjunct to gFOBT screening, but also as a primary screening test.

Footnotes

Competing interest: None declared.

References

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