Quantitative faecal immunochemical testing to guide colorectal cancer pathway referral in primary care

Colorectal cancer may be associated with a variety of symptoms, including blood in faeces. Small amounts of hidden blood in faeces (known as faecal occult blood) can show that there is bleeding from the gastrointestinal tract, potentially from malignant (cancerous) growths on the inner lining of the large intestine. Several other conditions (such as inflammatory bowel disease) may also cause blood in faeces.

Faecal immunochemical testing (FIT) detects small amounts of blood in a faecal sample using antibodies specific to human haemoglobin. A positive FIT result alone cannot confirm a diagnosis of colorectal cancer. Further assessment using colonoscopy or CT colonography is needed to confirm diagnosis.

Previously, NICE's guideline on suspected cancer recommended:

• offering FIT to adults presenting to primary care with 'low risk' symptoms of colorectal cancer, that is:

  • aged 50 and over with unexplained abdominal pain or weight loss

  • aged under 60 with changes in their bowel habit or iron-deficiency anaemia

  • aged 60 and over with anaemia even in the absence of iron deficiency

• using a suspected cancer pathway referral to immediately refer adults with 'high risk' symptoms, that is:

  • aged 40 and over with unexplained weight loss and abdominal pain

  • aged 50 and over with unexplained rectal bleeding

  • aged 60 and over with iron-deficiency anaemia or changes in their bowel habit

  • occult blood in their faeces shown by tests

• considering a suspected cancer pathway referral for adults:

  • with rectal or abdominal mass

  • aged under 50 with rectal bleeding and any of the following unexplained symptoms or findings:

    • abdominal pain

    • change in bowel habit

    • weight loss

    • iron-deficiency anaemia.

People referred to secondary care typically have further investigation using colonoscopy, or sometimes CT colonography. Clinicians have observed that many people on the suspected colorectal cancer referral pathway do not have any unusual findings at colonoscopy. So, using FIT could mean that people who are unlikely to have colorectal cancer may avoid colonoscopy, and that people who are more likely to have colorectal cancer can be prioritised more effectively. Colonoscopy capacity is limited, and there are sometimes long waiting times. Using FIT could reduce the number of people referred for colonoscopy and so reduce the waiting times for people on non-urgent referral pathways.

In 2022, the Association of Coloproctology of Great Britain & Ireland (ACPGBI) and the British Society of Gastroenterology (BSG) guidance on FIT in patients with signs or symptoms of suspected colorectal cancer recommended using:

• FIT for most people presenting to primary care with clinical features of colorectal cancer to guide referral for urgent investigation

• a threshold of 10 micrograms of haemoglobin per gram of faeces.
  
  The Scottish Government also made similar recommendations. The ACPGBI and BSG guidance was endorsed by NHS England and NHS Wales, and implementation has begun in some areas.

FOB Gold (Sentinel/Sysmex) is an automated quantitative immunoturbidimetric FIT system. It comprises faecal sample collection tubes that collect 10 milligrams of faeces in 1.7 ml of buffer, and latex agglutination reagent. FOB Gold is compatible with Sentinel's own SENTiFIT series of analysers and analysers manufactured by 5 other companies. The performance characteristics of the assay and throughput of the test vary depending on which analyser is used. The SENTiFIT 270 can run 270 samples an hour.

HM‑JACKarc (Minaris Medical/Alpha Laboratories) is an automated quantitative immunoturbidimetric FIT system. It comprises a sample collection device, designed to measure 2 mg of faeces in 2 ml of buffer, latex agglutination reagent, and buffer solution. The assay is compatible with the HM‑JACKarc analyser, which can process up to 200 samples an hour, with a maximum capacity of 80 samples per run.

The IDK Hemoglobin ELISA (Immundiagnostik) comprises:

• a microtiter plate, pre-coated with anti-haemoglobin antibodies

• buffers for washing, extraction and sample dilution

• conjugate peroxidase-labelled antibodies

• standards and controls

• tetramethylbenzidine substrate.
  
  The test requires a 15 mg sample of faeces. It uses an ELISA plate reader with a photometer (Dynex DS2 and DSX systems) to determine the result. The throughput of the test depends on which system is used to analyse the samples.

The company also produces the IDK Hemoglobin/Haptoglobin Complex ELISA, which is similar but uses a microtiter plate pre-coated with anti-haptoglobin antibodies.

IDK TurbiFIT (Immundiagnostik) is an immunoturbidimetric FIT assay compatible with a range of automated analysers from 16 manufacturers. The TurbiFIT kit comprises reagents, control samples and calibration samples. IDK TurbiTUBE sample collection devices are available separately and collect 15 mg of faeces in 1.5 ml of buffer. The performance characteristics and throughput of the assay vary depending on which analyser is used.

NS‑Prime (Alfresa/Abbott) is an automated quantitative immunoturbidimetric FIT system. It comprises a specimen collection container that collects 10 mg of faeces in 1.9 ml of buffer. The test is run on the NS‑Prime analyser. The NS‑Prime haemoglobin reagent is specific to the NS‑Prime analyser and cannot be used on other platforms. The NS‑Prime analyser can process 300 tests an hour with a maximum capacity of 220 samples per run.

OC‑Sensor (Eiken Chemical/MAST Diagnostics) is a quantitative immunoturbidimetric FIT system. It comprises faecal sample collection tubes, latex agglutination reagent and buffer. The OC‑Auto sampling bottles can hold 10 mg of faeces. The test can be run on either the OC‑Sensor PLEDIA or OC‑Sensor iO analysers, which differ in the number of samples they are able to process. Two other historical OC‑Sensor devices (DIANA and MICRO) were also included in this assessment and assumed to be equivalent to the other OC‑Sensor devices.

The OC‑Sensor PLEDIA can process up to 320 samples an hour with a maximum capacity of 200 samples per run. The OC‑Sensor iO can process up to 88 samples an hour with a maximum capacity of 20 samples per run. MAST Diagnostics states that the OC‑Sensor iO will be replaced by the OC‑Sensor CERES, which processes 90 samples an hour and has technical specifications equivalent to the OC‑Sensor PLEDIA.

The QuikRead go (Aidian) is a point-of-care analyser that can be used for a number of different diagnostic tests, including the immunochemical faecal occult blood test (iFOBT), which is an immunoturbidimetric test. The kits contain reagent capsules and buffer in prefilled cuvettes. Faecal sampling sets and control materials are supplied separately. A single sample of 10 mg of faeces can be run at a time, and the result is displayed in less than 2 minutes.

The comparator is standard care according to previous NICE guidance. This begins with clinical assessment of symptoms by a GP in primary care. People with low-risk symptoms were triaged using FIT and people with high-risk symptoms were immediately referred using a suspected cancer pathway referral (see section 2.3).

The reference standards used for assessing the accuracy of FIT are colonoscopy, CT colonography or long-term follow up.