A 55-year-old woman presents to her GP with a six-week history of loose stool. The patient has recently started on metformin, and her GP is confident that this is the reason for the change in bowel habit but is keen to exclude alternative diagnoses. Examination, including rectal examination, is normal. Blood tests confirm a normal haemoglobin and ferritin, and a FIT test reveals an undetectable faecal haemoglobin. Reassured by these findings, the GP explains that the bowel disturbance generated by the metformin is usually short-lived. She advises the patient to return if her symptoms persist, or if she notices other ‘red flag’ symptoms such as weight loss or bleeding but informs the patients that further invasive tests such as colonoscopy are not necessary.
The faecal immunochemical test (FIT) is a relatively new test to look for the presence of faecal haemoglobin. In contrast to the traditional guaiac faecal occult blood (FOB) test, it is a specific antibody against the human globin portion of the haemoglobin molecule – this is specific to humans and therefore enhances the test’s specificity. It also only requires a single stool test; FOB requires testing on three separate stool samples, which reduces compliance. It is a quantitative assessment of the amount of blood present – producing a number expressed as micrograms of haemoglobin per gram of faeces, as compared to a FOB ‘positive or negative’ result produced from a qualitative assessment of a colour change. The range will vary with the analyser, but typically varies from 10 to 150μg Hb/gF. Values below 10 are at the limits of the test and are often recorded by the laboratory as ‘undetectable’.
How to do a FIT
Like most patient-administered tests, technique is important. The stool sampled shouldn’t touch the toilet bowl water as cleaning products can interfere with the result, so patients may use toilet paper or an old food carton or disposable glove to avoid this. The FIT comes with a sampling device (a ‘picker’) that is stroked over the surface of the poo to collect a sample. Overloading the picker will again produce erroneous results.
When to use FIT
FIT has replaced FOB in two scenarios – symptomatic patients and screening participants. In bowel cancer screening, use of FIT increases participation by over 7%.1 It has been introduced in Scotland and is being rolled out to England and Wales in 2019. Because of issues with colonoscopy capacity, the level at which a FIT test is regarded as positive and therefore requiring investigation has been set in England to be approximately equivalent to the current sensitivity of FOB testing, at 120μg Hb/gF. This will knowingly miss a significant number of colorectal cancers present in the community (although probably less than are already missed by FOB) but will allow the screening programme to function without being flooded with additional referrals. In Scotland the figure has been set at the lower value of 80μg Hb/gF, so more sensitive for significant pathology but with larger numbers of colonoscopies required. The screening programme in England and Wales aspires to reduce the referral level of FIT to make it more sensitive in time, once more colonoscopy capacity is developed.
In the symptomatic population, FIT is very sensitive for the presence of colorectal cancer and has a very high negative predictive value – a negative FIT is very reassuring for the absence of cancer. Initial Scottish data2 have suggested a 100% negative predictive value for FIT and colorectal cancer (in other words, if faecal haemoglobin is undetectable, they do not have colorectal cancer). Subsequent studies have suggested the negative predictive value is less than 100%, but still very high (over 99%), and so called ‘FIT negative’ cancers have been described.2-6 Interestingly, these seem to be the symptomatically more obvious cancers such as those presenting as a rectal mass, with marked weight loss, or anaemia.
Supported by early data, NICE proposed an amendment to the initial NG12 guidelines. The NG12 guidelines7 described the symptoms that carry a 3% or greater risk of cancer (the ‘high risk’ group). NICE issued diagnostic guidance (DG30)8 for symptoms that carried a much lower (0.1-3%) risk of colorectal cancer and suggested that in this ‘low risk’ group, a positive test for the presence of faecal blood should mandate referral. Therefore, a lot of primary and secondary care organisations in the UK use FIT testing in this way – a positive FIT for the DG30 low risk group requires two-week wait referral, a negative result can reassure the patient.
Some organisations are going beyond NICE advice, however, and are using FIT testing for all patients with colorectal symptoms where colorectal cancer is a possibility, even in patients with NG12 symptoms, as they are reassured by the high negative predictive value for FIT. Initial data is encouraging and reassuring6, but it is always important to remember that FIT-negative cancers do occur, so safety-netting is important and if a cancer seems clinically likely (such as in the presence of a palpable mass, or iron deficiency anaemia), then the patient should probably be investigated anyway, regardless of the FIT result.
Because of the different levels of FIT used in screening and the symptomatic population, it is always important not to be falsely reassured by a negative screening FIT if your patient has colorectal symptoms. The presence of symptoms changes that patient’s risk of pathology, and it is important to remember that the level at which a screening FIT is regarded as positive (120μg Hb/gF) is much higher than in a symptomatic FIT (10μg Hb/gF).
How to use FIT safely
FIT is an effective triage tool for a patient with colorectal symptoms and vastly outperforms symptoms in terms of identifying presence or absence of cancer.9 All the current data points towards an undetectable faecal haemoglobin being strongly suggestive for the absence of colorectal cancer. Conversely, more significant colorectal pathology correlates with a high FIT, so patients with high FIT results (perhaps >120μg Hb/gF) should be strongly encouraged to have investigations. Effective safety-netting will vary from patient to patient. Repeating a FIT test is currently of unproven value so the safety-netting may take the form of offering a follow up appointment if symptoms don’t settle.
Dr Ed Seward is a consultant gastroenterologist at the University College London Hospital
- Moss S, Mathews C, Day TJ, et al. Increased uptake and improved outcomes of bowelcancer screening with a faecal immunochemical test: results from a pilot study within the national screening programme in England Gut 2017;66:1631–1644
- Mowat C, Digby, J, Strachan JA, et al. Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms Gut 2015;65:1463-1469
- Godber IM, Todd LM, Fraser CG, et al. Use of a faecal immunochemical test for haemoglobin can aid in the investigation of patients with lower abdominal symptoms Clin Chem Lab Med. 2016;54(4):595-602
- Högberg C, Karling P, Rutegård J, Lilja M: Diagnosing colorectal cancer and inflammatory bowel disease in primary care: The usefulness of tests for faecal haemoglobin, faecal calprotectin, anaemia and iron deficiency. A prospective study. Scand J Gastroenterol. 2017;52(1):69-75
- Widlak MM, Thomas CL, Thomas MG, et al. Diagnostic accuracy of faecal biomarkers in detecting colorectal cancer and adenoma in symptomatic patients. Aliment Pharmacol Ther. 2017;45(2):354-363
- Chapman C, Bunce J, Oliver, S et al. Service evaluation of faecal immunochemical testing and anaemia for risk stratification in the 2‐week‐wait pathway for colorectal cancer. BJS Open Epub ahead of print: 19.02.19
- Suspected cancer: recognition and referral. NICE guideline NG12 Published: 23 June 2015
- Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care. Diagnostics guidance DG30 Published: 26 July 2017
- Cubiella J, Vega P, Salve M, et al. Development and external validation of a faecal immunochemical test-based prediction model for colorectal cancer detection in symptomatic patients BMC Medicine 2016;14:128-141