Suspected cancer (part 2—adults): reference tables from updated NICE guidance

As part of a detailed, evidence-based document that represents an enormous amount of painstaking effort, NICE has recently issued referral guidance for suspected colorectal cancer (CRC) in which faecal occult blood testing (FOBT) is recommended for three subgroups of symptomatic patients who have a low statistical probability of harbouring CRC, either by virtue of their age or the nature of their symptoms (1).

This guidance has been summarised in the BMJ, and one of the “bottom lines” in this summary reads “in possible colorectal cancer, patients who do not meet criteria for suspected cancer referral should be offered testing for occult blood in faeces” (2).

The symptomatic groups identified in the guidelines as suitable for FOBT are:

1. Those aged 50 and over with unexplained abdominal pain or weight loss.

2. Those aged under 60 with change in bowel habit or iron-deficiency anaemia.

3. Those aged 60 and over who have anaemia even in the absence of iron-deficiency.

By way of background, faecal occult blood tests (FOBTs) are currently invariably analysed using a crude guaiac colorimetric method that is both non-specific and insensitive for the detection of blood in faeces. FOBTs have not been used in the management of symptomatic patients for many years and have been dropped from the repertoire of many laboratories. The faecal immunochemical test (FIT) for haemoglobin is a new version of FOBT that is 100x more sensitive and is specific for human globin and therefore not susceptible to diet or drug interference (3). Quantitative FIT are available in very few laboratories and their efficacy in symptomatic patients is subject to current research.

During the consultation process several groups expressed serious reservations about the use of a generic FOBT in the specified groups but, despite this, no change was made to the final document. Following publication of the guidelines, a letter was sent to NICE to ask them to reconsider the recommendation with respect to the use of FOBT. In response, the Director of Clinical Practice stated that the guidance was based on evidence and economic analysis and that positive FOBTs amongst the three symptomatic groups would be beneficial because their investigations would be expedited. The letter offered reassurance that individuals with false negative results will be subject to ‘safety netting’ and would be identified subsequently in urgent or routine GP referrals.

In the light of this reply, we wish to enumerate our concerns because we believe that the guidance is flawed and will lead to patients being falsely reassured and having investigations delayed. We make the following observations:

1. Patients falling into the three categories risk having FOBT and no other investigation. This is of particular concern for those under 60 with iron-deficiency anaemia. In this context, it is pertinent to point to NICE guidance on iron-deficiency anaemia which states that men and non-menstruating women of any age with unexplained iron-deficiency anaemia should be referred urgently for upper and lower gastrointestinal investigations (4).

2. The guidelines do not specify which FOBT is recommended. The guaiac FOBT only detects up to 50% of CRC in asymptomatic subjects (3) and is the only FOBT that is currently available, and then only in relatively few hospital laboratories. However, the relevant evidence cited in the guidance referred exclusively to qualitative tests and in five out of the six studies to the guaiac test. At the authors’ admission, the data from these studies were excessively heterogeneous and were not meta-analysed (1).

3. The guaiac FOBT-based CRC screening programme in England maximises clinical effectiveness by using a complex algorithm requiring up to nine stool samples (5). Consistent interpretation of the subjective guaiac FOBTs is only possible in laboratories where dedicated screening programme staff perform very large numbers of this test and where strict quality assurance is employed. The guaiac FOBT is a clinically and analytically poor test for all but marked and consistent rectal bleeding and it is only in this environment can it be utilised meaningfully, and only for screening asymptomatic populations.

4. Less than 2% of tests performed in the English ‘average-risk’ screening programme are designated positive (5) and it is likely that it will be similar for the patients meeting the criteria recommended for FOBT by NICE. Approximately 98% of the target group will therefore receive reassurance that their risk of CRC is similar to that of the general population.

5. To argue that this approach is cost-effective ignores the fact that anyone seeking advice about symptoms wishes reassurance that they do not have serious disease. As guaiac FOBT is not sensitive, this means that the vast majority of patients falling into the categories defined by NICE will be given reassurance on the basis of a spurious supposition. We are very concerned by the assertion that there will be adequate safety nets; in clinical practice negative tests provide reassurance to both patients and doctors, and where they are falsely negative diagnosis is likely to be delayed.

6. This non-specific guidance on FOBT comes at a particularly unfortunate time as there is increasing evidence that quantitative FIT used at an appropriate cut-off concentration will prove a valuable means of triaging symptomatic patients, including those who currently warrant urgent referral (6). At present, however, FIT is only available in a few specialist centres across the UK, and on a research basis only.

We are disappointed that NICE has chosen to ignore the advice given during the consultation period. We call for NICE to withdraw their recommendation to use FOBT in any symptomatic patients until there is a firm evidence base for the use of FIT at an appropriate cut-off and FIT analysers becomes widely available. If this request is not heeded, all we can do is to express our deep concern, and exhort GPs not to use currently available FOBTs to assist with the investigation of any symptomatic patients, but rather, in the words of the NICE guidance (2), to trust their clinical experience when deciding whether or not to refer a patient.

1. http://www.nice.org.uk/guidance/ng12
2. Hamilton W, Hajioff S, Graham J, Schmit-Hansen M. Suspected cancer (part2-adults):visual overview of updated NICE guidance. BMJ 2015;350:h2418 doi:10.1136/bmj.h2418
3. Young GP, Symonds EL, Allison J.E., et al. Advances in fecal occult blood tests – the FIT revolution. Digestive Diseases and Sciences 2015;60(3):609-22.
4. http://cks.nice.org.uk/anaemia-iron-deficiency#|scenariorecommendation:5
5. Logan RFA, Patnick J, Nickerson C et al. Outcomes of the Bowel Cancer Screening Programme (BCSP) in England after the first 1 million tests. Gut 2012; 61: 1439-46
6. McDonald PJ, Digby J, Innes C, Strachan JA, Carey FA, Steele RJC, Fraser CG. Low faecal haemoglobin concentration potentially rules out significant colorectal disease. Colorectal Dis 2013; 15; e151-9

Signatories:

Professor Robert Steele, President, Association of Coloproctology of Great Britain and Ireland

Dr Ian Forgacs, President, British Society of Gastroenterology

Dr Gwyn McCreanor, President, Association for Clinical Biochemistry and Laboratory Medicine

Sally Benton, Director, NHS Bowel Cancer Screening Southern Programme Hub and Consultant Biochemist, Royal Surrey County Hospital

Mr Michael Machesney, Chair of the Colorectal Cancer Clinical Reference Group, NHS England & Colorectal Pathway Director, London Cancer

Professor Colin Rees Vice President (Chair of Endoscopy) British Society of Gastroenterology, Chair of Research European Society of GI Endoscopy

Professor Stephen P. Halloran, Member of the Bowel Screening Advisory Committee and former Director of the NHS Bowel Cancer Screening Southern Programme Hub

Mr Muti Abulafi, Chair of the Colorectal Cancer Pathway Group, London Cancer Alliance

Deborah Alsina, Chief Executive, Bowel Cancer UK