Anne B Ballinger, Clive Anggiansah
are non-specific, and the stage of disease at diagnosis is
closely related to survival. In this review we discuss
disease presentation, criteria for urgent referral of
patients to specialist care, and recent developments in
the implementation of national screening programmes,
which aim to reduce mortality from this common
disease. Many general practitioners will also refer
patients with suspected colorectal cancer “direct to
test” and this review covers the various modalities for
investigation of patients with colorectal symptoms.
Sources and selection criteria
We searched PubMed for recent papers using the
keywords “colorectal cancer”, “screening”, “investiga-
In addition we used our personal reference archive.
How common is colorectal cancer?
In the Western world colorectal cancer is the second
the third most common in men after lung and prostate
and Australasia. In the United Kingdom the lifetime
incidence of colorectal cancer in people at average
risk is 5% and the age standardised incidence rate is
44.3 per 100000 population.3
How does colorectal cancer develop?
In most cases colorectal cancers arise from dysplastic
and repair DNA and the simultaneous activation of
oncogenes. This confers a selective growth advantage
to the colonicepithelial cell anddrivesthe transforma-
tion from normal epithelium to adenomatous polyp to
invasive colorectal cancer.4Germline (hereditable)
mutations underlie the well described inherited colon
a stepwise accumulation of somatic genetic mutations.
A single germline mutation in the APC tumour
suppressor gene is responsible for the dominantly
inherited syndrome, familial adenomatous polyposis
coli. It is characterised by the development of hun-
dreds to thousands of adenomatous polyps in the
colon and development of colorectal cancer and
other cancers in the third and fourth decade of life.
Clinical expression of the disease is seen when the
inherited mutation of one APC allele is followed by a
“second hit” mutation or deletion of the second allele.
Who is at greatest risk of colorectal cancer?
rectal cancer: 99% of cases occur in people aged more
than 40 and 85% in those aged more than 60 (fig 1). In
Europe the incidence of colorectal cancer is gradually
increasing, in part due to the ageing of the population
but also due to an increase in the age specific incidence,
suggesting that lifestyle or environmental factors, or
both, contribute. The much higher incidence of colo-
rectal cancer in more affluent countries compared with
less developed countries is also thought to be related to
lifestyle factors such as obesity and consumption of
processed meat, and an inverse relation with physical
activity and consumption of fruit and vegetables.
Next to age, family history is the most common risk
factor for colorectal cancer. Familial adenomatous
polyposis and hereditary non-polyposis colorectal
cancer are the most common of the familial cancer
for fewer than 5% of cases. About 10-20% of patients
describe a family history of colorectal cancer, but the
pattern of inheritance and clinical features are not
consistent with one of these well characterised
syndromes (table 1).5
What are the symptoms of colorectal cancer?
Abdominal pain, change in bowel habit, and rectal
bleeding or anaemia are the commonest presenting
symptoms of colorectal cancer but these symptoms
also commonly occur in other gastrointestinal
presenting symptom for left sided cancers caused by a
progressive narrowing of the bowel lumen, with
diarrhoea, a change in stool form, and eventually
intestinal obstruction. About 10% of patients with
iron deficiency anaemia have colorectal cancer, most
men, and women who are not menstruating, is an
indication for urgent referral and investigation.78
In 2005 the National Institute for Health and
Clinical Excellence issued updated UK based guide-
lines that outlined signs and symptoms warranting
Homerton University Hospital NHS
Foundation Trust, London E9 6SR
Correspondence to: A B Ballinger
BMJ | 6 OCTOBER 2007 | VOLUME 335 715
For the full versions of these articles see bmj.com
urgent referral(within two weeks) for further specialist
review or investigation of suspected colorectal cancer
How should suspected colorectal cancer be
Table 3 summarises the advantages and disadvantages
for examining the whole colon require full preparation
of the examination depends on adequate preparation.
Computed tomographic colonography (virtual colono-
scopy) provides an endoluminal view of the colon simi-
lar to that of traditional colonoscopy. Technical
improvements with this method (intravenous contrast
material and oral faecal tagging agents) may allow stool
forpriorbowel preparation. The probabilityof colorec-
lesion in the left colon (change in bowel habit or fresh
rectal bleeding) but who do not have polyps or cancer
visible at flexible sigmoidoscopy. Thus this may be an
ple, fresh rectal bleeding only in patients aged less than
50 years—but otherwise the entire colon should be
Patient choice is an important factor in deciding on
type of investigation. Prospective studies of patients
who underwent two,orin somecasesthree,consecutive
ography and standard colonoscopy were equally accep-
table, and both were preferable to double contrast
barium enema.1516Plain computed tomography of the
abdomen is a useful investigation in patients with a
Frail and elderly patients
Conventional colonic imaging tests may be difficult to
carry out in elderly or frail patients because of
immobility and poor tolerance to bowel preparation.
Prospective studies with clinical outcome at 12-30
months have shown that in patients with symptoms
plain computed tomography of the abdomen with oral
for detection of colon cancer of 88-94%.1718Equivocal
tests may need further investigation.
Testing for faecal occult blood and measurement of
serum tumour markers such as carcinoembryonic
antigen are not useful in the investigation of suspected
colorectal cancer. Faecal occult blood testing is an effec-
tive means of population screening in asymptomatic
people but it is too insensitive to guide the investigation
of patients with colonic symptoms. Similarly, tumour
in the follow-up of treated patients. Wireless capsule
endoscopy for imaging the colon is currently under
How is colorectal cancer managed?
Staging of the disease and complete visualisation of the
colon are required once colorectal cancer is diagnosed,
other than in the emergency setting. Liver and chest
imaging, usually with computed tomography, is
necessary to detect metastases, and a complete colonic
assessment can detect synchronous cancers, present in
3-5% of patients. Endorectal ultrasonography or
magnetic resonance imaging is also necessary to stage
rectal cancer. Surgical resection for localised colorectal
chemotherapy offers a survival benefit for patients after
Table1 | Lifetimeriskofdyingfromcolorectalcanceraccordingtofamilyhistory,and
Lifetime risk of
Refer for colonic
Risk in general population1:50No
One first degree relative affected (any age)2-3-fold increasedNo
One first degree relative affected (age <45 years)*3-4-fold increasedYes
Two first degree relatives affected (any age)3-4-fold increasedYes
*Initial colonoscopy is recommended between the ages of 35 and 40 years, or 10 years before the age of
cancer diagnosis in the family member if this is earlier. American guidelines use a cut-off value of <60 years.
Age at diagnosis (years)
Rate per 100 000 population
10-1420-24 30-3440-44 50-5460-6470-74
Fig 1 | Age specific incidence of colorectal cancer in men and
women. Adapted from Cancer Research UK (http://info.
Table2 | ReferralguidelinesfromtheNationalInstituteforHealthandClinicalExcellencefor
Symptoms and signs
Rectal bleeding with change in bowel habit to looser stools or increased frequency of
defecation, or both, persistent for six weeks
Definite palpableright sidedlowerabdominalmassconsistent withinvolvementoflarge
Definite palpable rectal (not pelvic) mass All
Rectal bleeding persistently without anal symptoms*
Change of bowel habit to looser stools or increased frequency of defecation, or both,
without rectal bleeding, persistent for six weeks
Iron deficiency anaemia without obvious causes (haemoglobin level <110 g/l in men or
<100 g/l in women who are not menstruating)‡
*Include soreness, discomfort, itching, lumps, prolapse, and pain.
†60 years is considered maximum age threshold. Local cancer networks may elect to set lower thresholds (for
example, 55 or 50 years).
‡British Society of Gastroenterology recommends urgent referral and investigation for any level of iron
716 BMJ | 6 OCTOBER 2007 | VOLUME 335
resection of stage II disease and selected patients with
stage III disease. Preoperative chemoradiotherapy
improves survival compared with surgery alone for
rectal cancer. Palliative chemotherapy can alleviate
in patients with metastatic colorectal cancer.19In some
What is the prognosis of colorectal cancer?
The outcome of colorectal cancer depends on the stage
toms are at Dukes’s stage C or D (table 4).2021Five year
survival rates are lower in the United Kingdom, Den-
mark, and eastern European countries compared with
the European average of about 50%.22Analysis of the
EUROCARE data (European cancer registries study)
suggests that lower survival in the United Kingdom
results from later stage at presentation and diagnosis
rather than inferior treatment for a similar stage.23
Who should enter a screening programme?
Healthy asymptomatic people with a family history of
colorectal cancer should be considered for screening
(table 1).56Conventional colonoscopy remains the
ideal investigation but computed tomographic colon-
ography is used to examine the remaining colon when
colonoscopy is incomplete—for example, as a result of
technical difficulties preventing passage of the scope.
adenomatous polyps thus preventing subsequent devel-
opment into invasive cancer.
People with one of the defined genetic family cancer
syndromes—for example, familial adenomatous poly-
posis or hereditary non-polyposis colorectal cancer—
have a high risk of colorectal cancer and should be
referred to a local clinical genetics unit for possible
formal counselling and mutation analysis of the
respective gene. Hereditary non-polyposis colorectal
cancer is the commonest of the family cancer
syndromes and is caused by a DNA mismatch repair
tion that predisposes patients to colorectal and also
extra-colonic cancers (endometrial, ovarian, genito-
urinary, small bowel, and biliary tract).
Inflammatory bowel disease
Patients with longstanding total ulcerative colitis and
Crohn’s colitis are also at risk for colorectal cancer.
National guidelines recommend that colonoscopic
surveillance should begin after 8-10 years for pancolitis
gests that surveillance reduces death from colorectal
cancer associated with irritable bowel disease.24
What are the methods for screening populations for
Population screening for colorectal cancer has been the
subject of several recent high quality controlled clinical
trials. The most widely investigated screening modality
is followed by imaging of the whole colon, usually with
colonoscopy.Cancersdetected by suchscreening are at
an earlier stage (mostly Dukes’s A and B) than
Table3 | Comparisonofcurrentmethodsforexaminingthecolon
Sensitivity for detection (%)
(>10 mm) Cancer
Usually2:1000* Yes98 97
Flexible sigmoidoscopy Rarely1:10 000* YesExamines left
Double contrast barium
No1:10 000 No 4883-94
*Highly operator dependent. Many expert endoscopists have lower rates than in quoted published series.
Invitation for faecal occult blood testing to 60 to 69 year olds
Positive result, 2%
Negative result, 98%
Re-enter programme, repeat test at 2 years
Normal or benign
Fig 2 | Expected outcomes in bowel cancer screening
Table4 | ApproximatefrequencyandfiveyearrelativesurvivalbyDukes’sstage20
Dukes’s stage modified
(equivalent TNM stage) Description5 yearly survival rate (%)
A (stage I)Localised to mucosa and submucosa 93
B (stage IIA and IIB)Extending into or through muscle layer
without lymph node involvement
C (stage IIIA-C) Lymph node involvement 44-83
D (stage IV)Distant metastases8
TNM=tumour, node, metastasis staging system.
BMJ | 6 OCTOBER 2007 | VOLUME 335717
symptomatic cancers (table 4).20Meta-analysis of four
randomised controlled trials has shown that screening
using faecal occult blood testing reduced the risk of
death from colorectal cancer by 25% of those screened.
It is estimated that screening using faecal occult blood
testing will avoid about 1 in 6 of deaths from colorectal
cancer.25Ongoing studies should prove if removal of
polyps reduces the subsequent development of colorec-
tal cancer. The National Health Service bowel cancer
occult blood testing are sent to people aged 60-69 years
oscopy at their local designated screening centre (fig 2).
sigmoidoscopy every five years with or without faecal
in people from age 50 years, reduce mortality from
colorectal cancer compared with no screening and
the cost per life saved compares favourably with
mammography for women aged more than 50 and
treatment of moderate hypertension. No single
strategy has, however, proved to be the most effective
or cost effective for screening.27American guidelines
recommend that people at average risk should be
offered one of these screening strategies from age 50
and thusat a younger age than in the United Kingdom
but at a higher cost per life saved.5
Contributors: ABB and CA participated in the literature search and writing of
the article. ABB is the guarantor.
Competing interests: None declared.
Provenance and peer review: Commissioned and externally peer
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Cancer Research UK (http://info.cancerresearchuk.org)—Colorectal cancer and other
cancers covered in detail
The lifetime risk of developing colorectal cancer is about 5%
Increasing age and a family history of colorectal cancer are the greatest risk factors for the
urgently in a specialised unit
Colonoscopy and computed tomographic colonography are of equal sensitivity for detection
of colorectal cancer
Colonoscopy allows biopsy of suspicious lesions and removal of polyps
Population screening by testing for faecal occult blood has begun in the United Kingdom
718BMJ | 6 OCTOBER 2007 | VOLUME 335