Two types of fecal occult blood tests (FOBTs) are commonly used: guaiac FOBT (gFOBT) and fecal immunochemical test (FIT). gFOBT is designed to detect occult blood in stool but is not specific for blood. It uses the peroxidase activity of hemoglobin to detect the presence of blood in stool. Dietary substances with peroxidase activity, such as plant peroxidases and red meat, can produce a positive test result. Antioxidants such as ascorbic acid can suppress any peroxidase activity and as such can cause false negative results. FIT uses antibodies specific for human hemoglobin (globin chain content) in stool and, therefore, is less likely susceptible to effects of nonhuman hemoglobin peroxidase activity (plant peroxidases, nonhuman sources of hemoglobin, and medications) (1). FIT has become the preferred version of FOBT and has started being used even for symptoms evaluation.
FOBTs are the primary modality for colorectal cancer (CRC) screening in much of the world, apart from the United States. Use of FOBTs for CRC screening is based on multiple randomized controlled trials. However, based mostly on theoretical considerations (“detecting blood”), anecdotal personal experiences of practitioners, and a few observational studies, FOBTs continue to be widely used for evaluation of gastrointestinal symptoms including gastrointestinal bleeding in the United States and the rest of the world (2,3). There have been multiple studies, including those by our group, documenting inappropriate use and recommending discontinuation of FOBT use for evaluation of gastrointestinal symptomatic patients (2–4). Nevertheless, up to now, there were no systematic reviews synthesizing the results of studies evaluating FOBT for diagnostic purposes.
In this issue of the journal, Lee et al. report on a well-performed systematic review and meta-analysis to assess the performance characteristics of FOBT as a diagnostic test for clinical indications. All included studies had reported results of additional diagnostic testing, allowing determination of sensitivity, specificity, and relative risks of outcomes among FOBT-positive vs FOBT-negative groups. The supporters of the use of FOBTs for evaluation of symptoms will note a pooled sensitivity of 0.83 (95% CI: 0.72–0.90) and a relative risk of 13.03 (95% CI: 8.36–20.32) for CRC diagnosis with a FOBT-positive result among those with iron deficiency anemia (IDA). Before these results are used to triage the performance of endoscopy (or even timing of endoscopy) for those with IDA, it is important to recall 42% of those with treatable lesions had negative FOBT and therefore would have been missed by an approach of endoscopy only in those with positive FOBT. An approach to decide to delay endoscopy based on negative FOBT would have delayed care for these 42% with treatable lesions in the setting of IDA.
Furthermore, of those with negative FOBT in the setting of IDA, 18.4% had treatable lesions and 1.2% had CRC. The pooled results suggest 17% of those with CRC in the setting of IDA will have a negative FOBT. Endoscopy for individuals with negative FOBT in the setting of IDA may, therefore, lead to more CRC and other treatable lesions diagnosis than repeated colonoscopy for asymptomatic average risk CRC screening or among those with a history of low-risk adenomas. Thus, even adjusting the timing of endoscopy based on FOBT results among those with IDA could be problematic.
It is important to note there was no major difference between FIT and gFOBT performance in the setting of IDA in the current review. Therefore, this review does not support the use of FIT for evaluation of individuals with IDA. There were no studies which reported on concomitant diagnostic tests and FOBT for evaluation of gastrointestinal symptoms, such as abdominal pain, and thus, the use of FOBT (gFOBT or FIT) for symptoms cannot be supported either.
In pooled analysis, FIT did have moderate sensitivity and specificity in predicting endoscopic activity among those with ulcerative colitis. Additional studies are, therefore, required to determine performance of FIT, especially in combination with fecal calprotectin for following up individuals with inflammatory bowel disease.
Previous studies have shown that although FOBT is commonly used in hospitals, the results are often ignored. In a city-wide study, assessing FOBT in 6 hospitals, we reported that 56% of those with positive FOBT never had an endoscopy during their hospital stay (4). Other studies suggest that FOBT may delay relevant investigations while waiting for the result of the test (2,5–9).
Proponents of FIT use in the assessment of CRC in the setting of lower bowel symptoms concede that a lot of work is needed before the verdict can be made on its utility because cases can be missed and standardization of assays is problematic (10). The miss rate documented in the current study is indeed problematic and supports our decision several years ago to discontinue the availability of FOBT for diagnostic evaluation in Manitoba's provincial laboratory system. Discontinuation of gFOBT in hospitals was easy to implement by having a requirement gFOBT would not be processed unless 3 samples, each from a separate day, were sent to the laboratories. For the rest, ongoing information dissemination has been necessary.
High-value care means providing the highest quality care at the lowest cost, where quality is defined as “the degree to which health services for individuals and populations increase the likelihood of desired health outcomes and are consistent with current professional knowledge (11).” Consequently, a strong case can be made that the use of FOBT in symptomatic or diagnostic non-CRC screening setting is low value care and, therefore, should not be part of the clinical assessment tools. This could not be truer in this era of resource stewardship and Choosing Wisely.
Based on the current state of evidence, we propose all hospitals and diagnostic laboratories stop providing FOBT (gFOBT or FIT) for diagnostic purposes and direct their resources to other more useful tests. This has to be a decision at the hospital and laboratory level, rather than being left to individual healthcare providers. Assessment of disease activity in inflammatory bowel disease with FIT should be limited to research studies for now.
CONFLICTS OF INTEREST
Guarantor of the article: AbdulRazaq Sokoro, PhD, FCACB, FAACC, and Harminder Singh, MD, MPH, FRCPC.
Specific author contributions: A.S.: Initial draft and revision. H.S.: initial draft and revision of the manuscript
Financial support: None to report.
Potential competing interests: A.S.: None. H.S. has been on advisory board of Takeda Canada, PendoPharm, Ferring, Merck Canada, and Guardant Health, Inc. and has received educational grant from Ferring and research funding from Merck Canada.
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