FIT as screening or triage of 2ww lower GI referrals

FIT as screening/triage of 2ww lower GI referrals

• the use of FIT in this setting is not - at present - NICE approved
• various studies using FIT alongside 2ww lower GI referrals have not shown 100% sensitivity - ie some patients with a negative FIT test have been shown to have colorectal cancer
• Mowat et al (1) used a FIT down to a level of a level of 10 µg Hb/g faeces and revealed a sensitivity of 89% in the equivalent of a 2ww population - ie 11 out of 100 patients with colorectal cancer had a negative FIT to a level of 10

Making Sense of the Statistics in use of FIT in the 2ww lower GI referrals

It is important to differentiate the statistics used to describe the efficacy of using FIT as a means of "triaging" (or prioritising):

• the manufacturers of FIT kits emphasise "negative predictive value" (NPV)
• NPV = True negatives/ True negatives + False negatives
  • the quoted NPV for use of FIT in patients satisfying NG12 (2 week wait lower GI referrals) is 99% plus
  • the significance of using NPV in this clinical scenario is that the 2ww pathway is based on a 3% prevalence of cancer in referrals from primary care. This means that the True negatives = 97%. The higher the value of True negatives in a population, the higher the NPV - no matter how effective a test is at identifying at identifying a condition (in this case a colorectal cancer). The prevalence of colorectal cancer in this referral population means the "worst" level of NPV that could be identified is 97% when it does not identify any cancers in the referral population (True negatives (97)/ True negatives (97)+False negatives (3))
  • to put this in context - Coeliac disease has a prevalence of 1%, therefore any test (based on anything - even the colour of a person's front door) would have a NPV of 99% as a test to diagnose Coeliac disease - this illustrates how NPV is influenced by disease prevalence; and is an incorrect statistic in a low disease prevalence population
    • thus the 99% plus stastistic for NPV in a low prevalence population such as the NG12 lower GI referrals does not seem so significant (3)
      
      
• the efficacy of test in terms of what proportion of the possible colorectal cancers are identified by FIT is "sensitivity"
  
  
  • Sensitivity = True positives / True positives + False negatives
    • this is how effective a test at identifying the condition concerned
    • NICE have stated that FIT at a level of 10 identifies approximately 90% of colorectal cancers when used in parallel to colonoscopy in the 2ww pathway - this was summarised in an NHS England letter from Peter Johnson on 10 August 2020 that stated "..safety netting must be in place because up to 10% of people with colorectal cancer present with FIT<10ug/gm..." (4)
      
      
• duplicate faecal immunochemical testing in patients at risk of colorectal cancer (5)
  • in this study:
    • all adult patients referred from primary care with suspected CRC with low-risk symptoms defined by NICE DG30 criteria were asked to complete two FIT samples on different bowel motions between August 2017 and June 2020 prior to clinical assessment in secondary care. After June 2020 all patients, including those with higher risk symptoms defined by NICE NG12 criteria, were included to facilitate decision-making and risk stratification for colonic imaging by hospital specialists during the SARS-CoV-2 pandemic. Some Trusts included in the study do test patients with FIT if they have rectal bleeding, whereas other Trusts do not. Patients with rectal bleeding were not delayed in their referral as urgent referral was made simultaneously to FIT requests
    • study results:
    • 2% of patients with colorectal cancer had two negative FIT tests (7/319)
    • 91 % of patients with colorectal cancer had two positive FIT tests (290/319)
    • 7 % of patients had one out of two FIT tests as positive (22/319)
    • i.e. only 2% of colorectal cancers in the study had two negative FIT tests at a level of 10ug/gm
      
      
• FIT - a study evaluated whether faecal immunochemical testing (FIT) can rule out colorectal cancer (CRC) among patients presenting with 'high-risk' symptoms requiring definitive investigation (6):
  • 3,596 symptomatic patients referred to the standard urgent CRC pathway were recruited in a multi-centre observational study
  • completed FIT in addition to standard investigations. CRC miss rate (percentage of CRC cases with low quantitative faecal haemoglobin [f-Hb] measurement) and specificity (percentage of patients without cancer with low f-Hb) were calculated
  • 9 had CRC. At f-Hb<10µg/g, the miss rate was 16.7% (specificity 80.1%). At f-Hb <4µg/g, the miss rate was 12.2% (specificity 73%), which became 3.3% if low FIT plus the absence of anaemia and abdominal pain were considered (specificity 51%)
  • study authors concluded:
    • FIT alone as a triage tool would miss an estimated 1 in 8 cases in our study (1 in 14 from meta-analysis), while many people without CRC could avoid investigations. FIT can focus secondary care diagnostic capacity on patients most at risk of CRC, but more work on safety netting is required before incorporating FIT triage into the urgent diagnostic pathway

For further information:

• CRUK Health Professional FIT Symptomatic webpage

Reference:

• Mowat et al (2015). Faecal haemoglobin and faecal calprotectin as indicators of bowel disease in patients presenting to primary care with bowel symptoms. Gut Online First, published on August 20, 2015
• NICE (2017). Quantitative faecal immunochemical tests to guide referral for colorectal cancer in primary care
• Personal Statement (Dr Jim McMorran, Editor in Chief, GPnotebook) (16/5/2020)
• NHS England (Professor Peter Johnson (National Clinical Director for Cancer NHS England and NHS Improvement), Dr Rober Logan (National Clinical Advisor for Endoscopy NHS England and NHS Improvement)) (10/8/20). Advice to local systems on triaging patients with lower gastrointestinal symptoms in the symptomatic service.
• Hunt N, Rao C, Logan R, et al. A cohort study of duplicate faecal immunochemical testing in patients at risk of colorectal cancer from North-West England. BMJ Open 2022;12:e059940. doi: 10.1136/bmjopen-2021-059940.
• Laszlo HE, Seward E, Ayling RM, Lake J, Malhi A, Stephens C, Pritchard-Jones K, Chung D, Hackshaw A, Machesney M. Faecal immunochemical test for patients with 'high-risk' bowel symptoms: a large prospective cohort study and updated literature review. Br J Cancer. 2022 Mar;126(5):736-743.