Screening and Early Detection of Colorectal Cancer

Colorectal cancers are common and need to be detected early to improve prognosis. Early diagnosis can be achieved by recognition and investigation of significant symptoms and by screening. Screening may be targeted at those who are at special risk and national screening programmes are being rolled out across the UK.¹

Early detection is important because:

• Colorectal cancer is common and has significant mortality:
  • In the UK, bowel cancer is the second commonest cause of cancer mortality.
  • Each year 34,900 people are diagnosed (about 1 per GP) - 63% in the colon and 37% in the rectum.
  • It causes 16,100 deaths per year.
  • The lifetime risk is about 5%.
• Early detection improves outcome:
  • Overall 5-year survival is around 50%, but early diagnosis improves survival.
  • Only 10% of colorectal cancers are diagnosed at Dukes' Stage A.
  • Early diagnosis may reduce morbidity.
  • Improved mortality by early detection can be appreciated from 5-year survival figures (see table below).

    Modified Dukes' Classification
    		5 year survival
    Dukes' A	Localised within bowel wall	83%
    Dukes' B	Penetrating bowel wall	64%
    Dukes' C	Spread to lymph nodes	38%
    Dukes' D	Distant metastases	3%

• It is achievable and is cost-effective. Early detection can be achieved by:
  • Identifying those at risk. For example the risk of colorectal cancer increases with age. 85% of cases occur in people over 60. 10% have a first-degree relative with the disease, and 6% have a genetic cause (e.g. familial adenomatous polyposis (FAP) and hereditary non polyposis colon cancer (HNPCC)) and these patients tend to present at a younger age.²
  • Case recognition through clinical awareness of the disease, including knowledge of those at risk, clinical presentations and when and how to refer.
  • Screening programmes (which may be general or targeted at particular "at-risk" groups).

The following factors increase the risk of developing bowel cancer:³

• Age - 85% of people who get cancer of the bowel are over 60.
• Family history of FAP or HNPCC.
• Personal history of previous bowel cancer.
• A previous adenomatous polyp.
• Ulcerative colitis and Crohn's disease.
• A diet high in red meat and fat.
• Being overweight.
• Smoking and alcohol.

In Crohn's disease and ulcerative colitis the risk is proportional to the duration and extent of the disease. At-risk patients should be referred for colorectal cancer surveillance and are discussed below under screening. Patients with iron deficiency anaemia should be investigated for colorectal cancer unless another cause for the anaemia has been identified.

It is important to identify symptoms which may be an early indication of colorectal cancer. It is also important to know how to manage such cases and when to refer.

Symptoms

Significant symptoms include:

• Repeated bleeding from the back passage.
• Persistent change in bowel habit (for 6 weeks).
• Abdominal pains (colic or tenesmus).
• Unexplained tiredness or weight loss.
• Iron deficiency anaemia.
• Passing mucus.

When to refer

The following recommendations presented in the table have been made:⁴

Such specific guidelines risk being misleading and confusing. It is important to consider other factors and the more general considerations.⁴ For example:

• Any patient who presents with symptoms suggestive of colorectal or anal cancer should be referred appropriately.
• Patients with equivocal symptoms who are not unduly anxious can be reasonably managed with a period of 'watchful waiting'.
• Patients with unexplained symptoms related to the lower gastrointestinal tract should always have a digital rectal examination (provided this is acceptable to the patient).
• In patients with ulcerative colitis or a history of ulcerative colitis, follow-up should be agreed with a specialist.
• There is insufficient evidence to suggest that a positive family history of colorectal cancer can be used as a criterion to assist in the decision about referral of a symptomatic patient.
• In patients with equivocal symptoms, a full blood count may help in identifying iron deficiency anaemia and hence urgency of referral.
• In patients for whom the decision to refer has been made, no examinations or investigations (other than abdominal and rectal examination, full blood count) are recommended, as this may delay referral.

Screening looks for evidence of a disease in people who have no symptoms, to find it at an early stage with a better chance of a cure. Screening is not a diagnostic test, and further tests are needed to make an accurate diagnosis. Colorectal cancer is eminently amenable to screening because it has a prolonged premalignant phase, it is relatively common, there are acceptable cost-effective screening tests, and early intervention can result in better outcomes. A screening test should be inexpensive, reliable, acceptable, simple to perform and amenable to rapid interpretation.
A screening programme is a public health service identifying individuals at sufficient risk of a particular disorder, who have not sought medical attention on account of symptoms, for further investigation or preventative action. Screening may be:

• Aimed at specific at-risk groups.⁸
• Aimed at a population according to age alone.

Screening in at-risk populations

These are more targeted screening programmes and protocols which select out sectors of the population at particularly high risk of colorectal carcinoma.⁸ These groups include patients with:

• Previous resection of a colorectal cancer.
• Previous colorectal adenomatous polyps.
• Inflammatory bowel disease.
• Ureterosigmoidostomy.
• Acromegaly.
• Family history of colorectal cancer.
• Specific genetic conditions:
  • HNPCC.
  • FAP.
  • Juvenile polyposis.
  • Peutz-Jeghers' syndrome.

Opportunistic screening (for example when new patients register with a new GP) should identify at-risk groups from past medical history and family history. Appropriate referral can then be made for either genetic advice or specialist colorectal follow-up.
The biggest number of high risk patients is found in the following groups of patients:⁸

• Patients with previous colorectal cancer.
• Patients with multiple or large (> or = 1 cm) adenomatous polyps.
• Patients with longstanding colitis.

Regular colonoscopy is recommended for people in all the at-risk groups, but the frequency with which this should be carried out depends on the particular condition.⁹ For example:

• Patients with a family history of FAP should be referred to a geneticist for DNA testing after the age of 15; if positive they need regular endoscopic surveillance.
• Patients with a family history of HNPCC (suspect if there are 3 cases in the family) should be referred for clinical screening at 25, and should see a geneticist.
• Patients with a first degree relative (sibling, parent or children) who had cancer diagnosed under the age of 45, means their lifetime risk is greater than 1:10 - refer for screening at 10 years younger than the youngest affected relative.
• For those with risk higher or equal to 1:10, referral to specialist services for screening should be made. There are guidelines on the management of high-risk groups available.¹⁰ In cases where there is doubt, referral for advice either to the local genetics services or to the local colorectal specialist should be considered.

Family history of colorectal cancer

Individual risk of colorectal neoplasia can be estimated empirically from family histories. It is important that the significance and detail of family history is appreciated so that appropriate screening and referral recommendations can be made. It is important to ask:

• The current age of the patient whose risk is being considered.
• The age at onset of each affected relative.
• The number and relationship of those affected relatives.

It is worth remembering that risk of colorectal cancer defined only by family history alone will not identify all those destined to develop colorectal cancer. In other words some people who are not offered screening because their family history does not indicate sufficient risk may be destined to develop colorectal cancer. Hence it is useful for patient and GP to appreciate relative risk and the fact that there is a residual risk even for those in a low-risk category (see table below).

Indirect evidence suggests a marginal benefit for large bowel surveillance for people with one first-degree relative affected by colorectal cancer aged < 45 years or with two affected first-degree relatives.¹⁰ Such patients should be considered at significantly increased risk and surveillance discussed. If such people also have other distant affected relatives, referral to the Clinical Genetics Services is appropriate. Those with a lesser degree of family history should be considered at insufficient risk to justify screening and be reassured.

• First-degree relative (FDR = siblings, parent, child)
• Second-degree relative (SDR = aunt, uncle, grandparent, nephew, niece)

There are some important points to remember when considering family history as a risk factor for colorectal cancer:¹¹

• Age is the most important risk factor for colorectal cancer. For example, the risk at the age 60 years exceeds the absolute risk for people aged 40 and 50 who have a significantly increased risk because of their family history.
• Studies have shown a substantial proportion of proximal neoplasms in people with a family. 30% of these would not have been identified by flexible sigmoidoscopy. There seems to be a particular risk of proximal lesions in women who have a family history. Thus, a full colonic assessment is recommended.
• Full colonic assessment is recommended also because of the option for simultaneous therapeutic intervention or biopsy (but barium enema with targeted follow-up endoscopy is an acceptable alternative).
• Even colonoscopy will miss 6% of adenomas 1 cm or greater.

Population screening

Faecal occult blood screening (FOB) is the only cost effective method of population screening. It is important to remember that a positive FOB result requires further assessment and testing.

• The UK Colorectal Cancer Screening Pilot Group used FOB testing to screen 478,250 people aged 50 to 69. 57% of those invited took part; 1.9% had positive results, and the detection rate was 1.62 per 1,000. Each FOB test cost £5 and the subsequent diagnostic colonoscopy cost £127.¹²
• FOB screening can reduce mortality by 16% despite compliance rates being only 50 to 60%. This reduction in mortality is partly due to the detection of early (Dukes' A and B) cancers and partly to an increase in colonic polypectomy.¹³
• Screening options after FOB testing include sigmoidoscopy, colonoscopy and barium enema. Using flexible sigmoidoscopy rather than colonoscopy will miss proximal lesions.¹⁴ Barium enema does not allow for simultaneous therapeutic interventions.

  Approximate Detection Rates
  PR examination	10%
  Rigid sigmoidoscopy	30%
  Barium enema	60%
  Flexible sigmoidoscopy	70%
  Flexible colonoscopy	85%
  CT colonograph	90%

The NHS Bowel Cancer Screening Programme

• The NHS Bowel Cancer Screening Programme is now being rolled out nationally and will achieve nationwide coverage in 2009.¹
• GPs are not directly involved in the delivery of the Programme but they will be notified when invitations for bowel cancer screening are being sent out in their area. They will also receive a copy of the results letters sent to their patients.
• People aged 60-69 will be invited to perform FOB tests at home every two years.
• People over 70 can request a screening kit by calling a freephone helpline.
• The programme could save 1,200 lives a year in England (9% of the 13,000 annual death toll). The cost is about £5,900 per life saved.¹⁵

In 2007 the Scottish Executive Health Department introduced a phased national bowel cancer screening programme.¹⁶ This targets males and females aged between 50 and 74 years for a 2-yearly home FOB test. Follow-up for positive tests is with further assessment and colonoscopy.
Contacting people by telephone has been shown to improve attendance for screening from 39% to 63%.¹⁷

• FOB tests need to be performed repeatedly, which may lead to reduced uptake and effectiveness.
• Assuming that 60% of those offered screening take it up, the programme will generate an extra 30,000 colonoscopies in a service that is already overstretched.
• The complications of colonoscopy are perforation and haemorrhage (1 in 1,000 procedures for each) and these assume significant proportions with 30,000 extra screening colonoscopies per year.
• Experienced staff conduct the colonoscopies during a trial but, in real life, non-specialists would undertake many of the colonoscopies and so more cancers may be missed.
• About half of all colonoscopies carried out on the basis of a positive test result show no evidence of cancer (how would such patients be followed up?).
• False positive FOB tests (18 per 1,000 tests) will create anxiety.
• Simply brushing teeth the morning before the test can give a positive result. FOB is not a specific test.
• 8% of men are colour blind and may not be able accurately to interpret the FOB test (not relevant with the NHS Bowel Cancer Screening Programme as samples are read elsewhere).
• Screening may substantially increase the workload for GPs.¹⁸