Should fecal hemoglobin be a component of the routine laboratory repertoire?

The following post was written to update a previous Short. Please see the past Short on this topic here.

Colorectal cancer (CRC) remains a major global health problem. Although the incidence of CRC varies widely across the world, the majority of CRC deaths occur in countries with a high or very high Human Development Index (HDI).1 Interestingly, while incidence and mortality have either stabilized or declined in countries with the highest HDI, including the United States and several Western European countries, marked increases in both have been observed in Asia, South America, and Eastern Europe and, very importantly, in younger individuals less than 45 years old, most likely due to lifestyle factors.2 The reductions seen in high HDI countries may be due to improved access to high-quality treatment and earlier diagnosis through (a) screening and (b) prompt investigation of patients presenting with symptoms.

Screening asymptomatic individuals for CRC, either opportunistically or programmatically, has expanded worldwide over recent years. There are many modalities available for screening. Although there is interest in the multi-target stool DNA test (Cologuard) and a plasma SEPT9 DNA methylation test (Epi proColon), and other fecal, blood microRNA, and CRC-related gut microbiome screening markers are under much research and development,3  tests for the presence of blood in feces are widely considered the best currently available non-invasive screening strategy. The traditional guaiac-based fecal occult blood test (gFOBT) is now deemed obsolete, and fecal immunochemical tests for hemoglobin (FIT), particularly quantitative FIT, are favored.4  Many countries, including Scotland, have evolved CRC screening from gFOBT to FIT with significant benefits, particularly in the uptake of the test.5

In a recent study of 29766 patients diagnosed with CRC, only 9.6% were detected through screening, and more than half (53.8%) were referred from primary care.6 However, although lower gastrointestinal (GI) symptoms are very common presentations in primary care, CRC is relatively rare. In this clinical setting, symptoms are very poor indicators of the presence of significant colorectal disease,7 even rectal bleeding.8 Amongst other reasons, encouragement from governments in the United Kingdom (UK) to the general public to seek care if they experience lower GI symptoms has led to large and ongoing rises in the number of referrals to secondary care for colorectal visualization, usually colonoscopy. A consequence is that, since there is limited endoscopy capacity in the UK and in many other countries, waiting times for investigation have increased leading to some risk of later stage presentations of CRC.9

The solution to this major problem, which has been significantly exacerbated with the current COVID-19 restrictions on endoscopy, is to use FIT in the assessment of patients presenting in primary care with lower GI symptoms. There are now many reports and reviews on the value of quantitative measurement of fecal hemoglobin concentration (f-Hb) in this clinical setting.10 The experience in Tayside, Scotland, since a routine service using FIT was initiated, following the novel first ever diagnostic accuracy study11 and then a pilot investigation,12 has been documented in detail.13 The conclusion was that FIT can be introduced into routine clinical practice in primary care as an adjunct to clinical assessment and a full blood count. A f-Hb <10 μg Hb/g feces, in the absence of iron deficient anemia, a palpable mass, or persistent severe diarrhea, identifies patients with an extremely low risk of developing CRC, who require reassurance rather than further investigation. However, it is important that “safety-netting” strategies are in place so that those patients with f-Hb below the threshold applied for further investigation, who continue to have symptoms or have exacerbation of symptoms, are monitored and treated appropriately.

It is firmly believed that it is timely that FIT should become integral to the assessment of all patients presenting to primary care with new GI symptoms to objectively, efficiently, and effectively determine the risk of underlying significant colorectal disease (CRC, advanced adenoma, and inflammatory bowel disease ([IBD]) and to encourage direction of colorectal visualization to those patients who would benefit most. The results of many studies support this view. FIT has rapidly rolled out across the UK as a routine investigation. Governments, including in Scotland,14 have urged their use. And the threshold used to stimulate further investigation can be set to give the percentage of presenting patients appropriate to the available reources.15  FIT in this clinical context is also widely used in other countries such as Sweden16 and Spain17 and, anecdotally, in primary care in many other countries.

The current use of FIT for the triage of patients with lower GI symptoms probably depends on the availability of colonoscopy and other means of colorectal visualization, and undoubtedly also on the organization of the local, regional, or national approaches to health service provision, but all are commended to offer f-Hb estimations as a component of the routine laboratory repertoire. Further, in the future, it is likely that f-Hb will become more and more used, not only in screening for, and detection of, colorectal neoplasia, but also in the diagnosis and monitoring of patients with IBD, particularly ulcerative colitis.18 In addition, an intriguing possibility is that, in individuals who have the common finding of detectable f-Hb but no significant disease on colorectal visualization, this is associated with a range of common chronic conditions which have a systemic inflammatory component; f-Hb might have potential in identifying individuals who are high risk of developing chronic conditions or are at an early stage of disease.19

REFERENCES

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