Critical considerations of fecal occult blood tests for colorectal cancer

Abstract

Colorectal CancerVol. 2, No. 1 EditorialFree AccessCritical considerations of fecal occult blood tests for colorectal cancerRobert JC Steele & Jayne DigbyRobert JC SteeleUniversity of Dundee, Nethergate, Dundee, DD1 4HN, Scotland, UK. Search for more papers by this authorEmail the corresponding author at r.j.c.steele@dundee.ac.uk & Jayne DigbyUniversity of Dundee, Nethergate, Dundee, DD1 4HN, Scotland, UKSearch for more papers by this authorPublished Online:8 Feb 2013https://doi.org/10.2217/crc.12.74AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail The most commonly used strategy in colorectal cancer (CRC) screening programs involves the use of stool tests to detect occult blood, and guaiac fecal occult blood tests (gFOBTs) are, to date, the only fecal tests shown to reduce CRC mortality in population-based randomized trials [1]. However, gFOBTs also carry disadvantages. A major concern is that interval cancers account for around 50% of cancers detected in gFOBT screened populations [2] and recent data show that gFOBTs are less sensitive in women than in men, and in both rectal and right-sided cancers when compared with left-sided disease [2,3].In addition, the test is associated with a high false-positive rate with no neoplasia detected in around half of colonoscopies performed following a positive gFOBT [2,3]. This may be, in part, explained by the fact that gFOBTs are not specific for human hemoglobin (Hb) and are subject to possible dietary interference from, for example, red meat and high-peroxidase fruits and vegetables. As a result, it has been common practice to instruct participants to adhere to dietary restrictions ahead of sample collection, although this may act as a barrier to screening and affect participation rates [4]. However, data from a meta-analysis did not support dietary restrictions with gFOBTs, leading to recommendations that restrictions are abandoned to improve adherence rates [5].Fecal immunochemical tests (FITs) are now available and are increasingly being used in screening programs. Unlike gFOBTs, FITs are specific for the detection of human Hb, eliminating any potential for dietary interference, and are also more specific than gFOBT for lower gastrointestinal bleeding. In addition, modern FITs generally allow a more convenient method of sample collection, and are associated with better participation rates [6].Another major advantage of FIT is that automated versions not only eliminate interobserver variability, but also the quantitative nature of these tests allow provision of a measured fecal Hb concentration. Screening program organizers are therefore able to adjust the cutoff limit for positivity as appropriate to optimize sensitivity and specificity within available colonoscopy capacity. The benefits of this have been demonstrated by substantial reductions in positivity rates as the cutoff point increases, with only modest effects on detection rates of screen-relevant neoplasia [7].Quantitative FITs could potentially be used to select tailored cut-off points in screening programs according to factors shown to affect baseline fecal Hb concentration, such as age and gender [8]. An important study by Chen et al., showing that fecal Hb concentration at first screening can be a predictor of subsequent colorectal neoplasia, provides an argument in favor of adoption of risk-stratification methods into CRC screening programs [9]. Strategies could be applied to screening participants with a fecal Hb concentration just below the cutoff for investigation, such as shorter screening intervals to sooner detect high-risk lesions presenting as false-negative at initial screening. Conversely, those with very low or no fecal Hb detected could perhaps be invited for FIT screening at less frequent intervals, owing to the long preclinical phase associated with disease progression in CRC. A recent study by Omata et al. showed that fecal Hb concentration from quantitative FITs could also be used alongside gender and BMI in a scoring system to predict the probability of significant colorectal neoplasia in asymptomatic individuals [10]. These studies demonstrate the potential that quantitative FITs hold for improving clinical outcomes in future CRC screening programs.The clinical performance of FITs in comparison to gFOBT has now been investigated in randomized controlled trials. Van Rossum et al. found that 2.5-times more cancers and advanced adenomas were detected with FIT than with gFOBT [11], and Hol et al. concluded that FITs were a more effective screening tool than gFOBTs at all seven cutoff points examined owing to their superior performance with regard to both adherence and detection rate of advanced neoplasia [12]. Further studies have demonstrated significantly superior performance characteristics of FITs over gFOBTs [13–15], and FITs appear to be more sensitive for adenoma [16–18]. This latter quality is important, as the Nottingham trial of gFOBTs has not demonstrated a reduction in the incidence of CRC, presumably as a result of poor adenoma detection [19].Thus, the adoption of FITs in CRC screening programs has potential to address participation, appropriate positivity rates and the problem of false-negative results. A recent cost–effectiveness analysis found that FITs guarantees more efficient screening than gFOBTs [20]. However, despite the growing evidence in its favor, further work is warranted on the optimal use of the FIT in screening programs, particularly in settings where colonoscopy capacity is constrained.Financial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.References1 Towler B, Irwig L, Glasziou P et al. A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, Hemoccult. Br. Med. J.317,559–565 (1998).Crossref, Medline, CAS, Google Scholar2 Steele RJ, McClements P, Watling C et al. 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Health Care26(1),48–53 (2010).Crossref, Medline, Google ScholarFiguresReferencesRelatedDetails Vol. 2, No. 1 Follow us on social media for the latest updates Metrics Downloaded 252 times History Published online 8 February 2013 Published in print February 2013 Information© Future Medicine LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download