The Rising Incidence of Colorectal Cancer
A The incidence of colorectal cancer has been steadily increasing in both males and females over the last 20 years. It has become the most common cancer in Singapore with almost a thousand new cases diagnosed annually over the last few years. It is only second to breast cancer in the female and lung cancer in the male.
The lifetime risk for the average Singaporean is about 1 in 55. Singapore has one of the highest incidence of the cancer in Asia together with Japan, Taiwan and Australia. The incidence of colorectal cancer starts to increase rapidly from around the age of 50 years and screening is therefore usually targeted at this group of the population. Among the races in Singapore, the Chinese has a disproportionately high incidence of the disease. Symptoms
These include bleeding in the stool that is often painless, change in bowel habits, persistent diarrhoea, mucus in the stool, reduction of stool calibre, a recurrent need to defaecate (tenesmus), anaemia, an incidental abdominal mass and rarely, contrary to popular layman belief, pain. Intestinal obstruction occurs when the tumour is large with associated abdominal distension, lack of bowel opening, abdominal colic and vomiting.
From the statistics of the department which treats mainly symptomatic cases, at the time of diagnosis, more than half of the patients already has either distant metastasis to the lymph nodes or to other organs, making surgery alone inadequate recommended treatment. In contrast, about 10 percent has mucosal disease with greater than 95 percent five-year disease-free survival.
Detection of the cancer based on symptoms is obviously grossly inadequate. Natural history of colorectal cancer
Colorectal cancer has a pre-malignant phenotype (colonic adenomatous polyps) making early intervention possible. The natural history of the disease begins as a result of accumulated multiple genetic changes from environmental insults on the colonic mucosa. The individual’s genetic constitution may predispose a person to the speed of polyp development leading to cancer formation.
Examples are Familial Adenomatous Polyposis Coli (FAP) and Hereditary Non-polyposis Colorectal Cancer (HNPCC). Colorectal cancers are also known to cluster in a family but do not fall into the defined genetic descriptions.
These accumulated damages may lead to hyperplasia of the epithelium and the formation of colonic polyps, which are the visible precursor to colorectal cancer if allowed to progress with growth. The degree of dysplasia increases with the size and duration of the polyps. This was described by Vogelstein and his co-workers and is believed to account for the formation of over 90% of the colorectal cancers.
Invasion or spread from the malignant polyp is believed to occur contiguously (mostly via the lymphatics and direct infiltration) unlike in some cancers whereby metastasis occurs at an early stage of the disease. This translates to a better cure rate with earlier detection of the cancer before extensive spread.
This is supported by stage related survival data and by population screening data in Western countries where an earlier intervention (especially at the asymptomatic stage of the disease) is translated into better cure rates. The remaining cancers are believed to have arisen de novo with no precursor lesions or phenotype like polyps.
In its polyp form, before the onset of invasive characteristics, removal through colonoscopy will effectively abort the cancer formation process. This is the most effective prevention for colorectal cancer. It is believed that through this process of repeated surveillance and polyp removal that the incidence of colorectal cancer has stabilized in the US and has in fact seen a decline in recent years (from the National Polyp Study in the US and the SEER data.
Colorectal cancer screening
Cancer screening aims to detect the cancer or its precursors (i.e. colonic polyps) before the onset of symptoms. We do know that with earlier detection coupled with timely surgery, cure is possible.
In fact, colorectal cancer screening has shown:
(1) |
a greater number of earlier cancers (i.e. Stage I or II) detected and this is translated to better survival and cure rates; |
(2) |
a greater number of “high risk” colonic polyps detected and removed through the colonoscope before malignant change ; |
(3) |
to identify a relatively higher risk subgroup of individuals in the population with hitherto no risk factors but found to harbour asymptomatic polyps for regular surveillance. This will effectively keep the risk of developing any advanced cancers very low. |
Risk Factors
Risk stratification is very important. High risk individuals are those who has the following characteristics:
| (1) |
a personal history of resected colorectal cancer, |
| (2) |
a personal history of colonic polyps, |
| (3) |
a family history of genetic cancers like HNPCC or FAP, |
(4) |
a family history of colorectal cancer or colonic polyps in a first degree relative. Age above 50 years old is a risk factor. A history of second degree relatives with colorectal cancer may be considered as the same risk of the average population but may increase with the greater incidence of clustering of the disease in the family. High risk individuals should be followed-up by a doctor who can recommend regular surveillance. |
In Singapore, our lifetime risk is probably higher than individuals in the surrounding countries. Reliance on the onset of symptoms is ineffective screening and often do not result in detection of early lesions.
| Bedside clinical examination is ineffective for early disease. Currently, the available screening tests include: |
| (1) |
faecal occult blood test (FOBT), |
| (2) |
double contrast barium enema examinations (DCBE), |
| (3) |
flexible sigmoidoscopy (FS), |
| (4) |
colonoscopy, |
| (5) |
a combination approach (e.g. FOBT and FS). Effectiveness, cost, acceptability and risk involved in each modality are the main reasons for the different choices available. |
What is FOBT ?
All cancers and large polyps do intermittently bleed into the stool that is passed out. As the blood may be in minute quantities that may not be visible to the naked eye, a special test kit is required to detect this. This is the FOBT kit.
| Most kits work on one of the two principles: |
(1) |
through a chemical reaction making use of the reducing ability of haem (i.e. Fe2+). This is the guaiac test. A thin sample of stool is smeared onto a card with subsequent addition of a developing solution and a chromogen to the paper for a chemical reaction with colour change for a positive test. |
(2) |
through an immunochemical test using animal antibodies developed to detect either human haemoglobin / haem or human albumin in blood. A reducing chemical is coupled to the antibody that can result in a change in either colour or pattern that gives a positive test result.
These kits usually come with a small plastic “rod” attached to the cap that can be plunged into the stool for a sample and reinserted back into a buffer solution in the container before development using a filter paper strip coated with antibodies. |
As the guaiac-based test is a chemical test, false positivity may result from certain food substances that can react with the chromogen, e.g. raw meat, radish, broccoli, beet-root and drugs like vitamin C supplements.
Dietary restriction 2 days prior to sampling is essential if the guaiac-based test is used in order to reduce on false positivity rates. Hydrating the card before development will also increase the positivity rate.
On the other hand, the immunochemical test does not require any dietary restriction since they utilize the specific antigen-antibody reaction. As a result, these tests are also more sensitive than the guaiac test in picking up smaller quantities of blood and are more specific. The only haemoglobin they cross-react to is chimpanzee blood !
Three cards are used for the guaiac test and two kits for the immunochemical test annually. Any more frequent tests will result in a higher false positive rate. Any one positive test requires further evaluation with colonoscopy or DCBE. As the FOBT is a non-specific test, a positive result may not only be a false positive, but may also be due to other pathology like haemorrhoids which is ever so common in Singapore, diverticular disease, infective or ischaemic colitis, to name a few.
A negative test may just be a problem of sampling or that the polyp has not been bleeding. Care should also be taken during sampling to reduce false positive rates . These tests have a definite “miss-rate” variously quoted between 30% to 60% when used in the population screening setting.
What about endoscopy ?
The flexible sigmoidoscopy (FS) examines the left half of the colon to identify cancers (up to 70% of all colorectal cancers are within the reach of the FS) and polyps if detected has to be followed with a full colonoscopy.
This examination misses 30% of the lesions on the right side. Thus, some practitioner will combine this with the FOBT to increase its yield. A FS requires no full bowel preparation (an enema is sufficient) and is easily and safely performed by operators with little training eg. nurses or technicians. A colonoscopy is arguably the gold-standard in screening as the miss rate for this is low.
Lesions may also be removed for biopsy. The disadvantage is the cost and a minor risk of perforation in the region of 1 in 10,000. This incidence is probably lower in highly specialized units. The distinct advantage with colonoscopy is that no further follow up is required for the next 3-5 years if there is a normal scope.
Should a DCBE be considered ?
This is an x-ray based examination. The usual bowel preparation as in colonoscopy is required. A liquid barium sulphate contrast (x-ray opaque) is flowed under pressure per anum via a tube into the colon followed by air insufflation to distend and coat the mucosa with a thin layer of barium.
This can be rather uncomfortable. As this procedure studies “shadows”, the reliability depends on a pristine bowel preparation and how the radiographer performs the test. The American Society of Radiologists dictates that more than 95% of lesions must be detected with the DCBE as standard. Small lesions, however, are known to be missed. Any positive or suspicious lesions will require colonoscopic evaluation. The risk of perforation is lower than a colonoscopy, although not absent.
What about any new tests in the development for screening ?
The virtual colonoscopy (also known as the CT colonography) makes use of existing spiral CT scan technology and performs fine-cuts CT scanning and reconstruct it with a software programme. This allows a 3-dimensional examination and allows a “fly-through” effect just like performing a colonoscopy in the examination of mucosal lesions.
The value of this test in population screening is not known. Nonetheless, the usual bowel preparation is required and air is still insufflated into the colon to distend it. Suspicious lesions are followed up by colonoscopy. It has been shown to effectively localize polyps less than 5 mm in diameter.
Miniaturization or nano-technology has produced cameras that may be installed into capsules which can be swallowed. They will travel through the intestines and take videos that may either be stored in the capsule or transmitted out to a receiver around the waist for viewing.
This has been promising for evaluation of small intestinal lesions and trials are under way for its use in the examination of the colon. Population trials are also on the way in the US using faecal detection of tumour shed DNA. This approach is presumably more specific than occult blood detection.
The approach for colorectal cancer screening
The screening recommendations have been laid down in the MOH GCP on cancer screening (see figure 1).
Figure 1
Screening recommendations for the average risk
FOBT – annually
Flexible sigmoidoscopy – 5 yearly
Combined FOBT and flexible sigmoidoscopy – 10 yearly
Colonscopy – 10 yearly
Double contrast barium enema – 5 yearly
|
Risk stratification helps to identify the high risk groups, e.g. kindreds of FAP, HNPCC, individuals with a history of colonic polyps and a history of treated colorectal cancer (See figure 2).
Figure 2
Recommendations for screening people with increased risk
Familial adenomatous polyposis coil (FAP)
- start at puberty (10-12 years)
Hereditary non-polyposis colorectal cancer (HNPCC)
- every 1-2 years from 20 years old or 10 years before youngest age of diagnosis in the family
Individuals with history of adenomatous polyps and resected colorectal cancer
- annual scope till free of polyps and subsequent 3 yearly scopes
|
The family history of colorectal cancer and colonic polyps will further help (figure 3 and 4). A history of related cancers like endometrial cancer, ovarian cancer and urothelial cancers may also be related to colorectal cancer (Lynch II syndrome) and may run in the family with colorectal cancer.
Figure 3
Risk stratification
Has the patient had colorectal cancer or on adenomatous polyp?
Does the patient have an illness that predisposes to colorectal cancer? (eg ulcerative colitis, radiation colitis)
Has a family member had colorectal cancer or an adenomatous polyp?
- how many member(s), relation, age
|
Figure 4
Recommendations for screening of people with increased risk
People with family history of colorectal cancer or adenomatous polyps
Start at 40 years
- first degree relative < 60 years old or 2x first degree relatives
- first degree relative > 60 years ild or 2x second degree relatives
Population risk (start at 50 years)
- 1 x second degree relatives or third degree relatives
|
Conclusion
Colorectal cancer is common in Singapore and this is a preventable and treatable condition if detected early enough. However, as with many diseases in its early state, there are no obvious symptoms.
Thus screening is necessary to pick up these lesions. At the moment, except for the high-risk groups, there is no formal programme for screening and follow-up. Individuals will have to discuss this with their family physician and have to voluntarily avail themselves for the various tests.
March has been designated the Colorectal Cancer Awareness Month organised by the Singapore Cancer Society. Forums for educating the public as well as media blitz on national television and radio will be conducted. Free FOBT kits will be given out to eligible individuals for screening at all polyclinics in Singapore and at participating GP practices.
Dr Tang Choong Leong
Senior Consultant Surgeon and Director, Polyposis Registry
Department of Colorectal Surgery, Singapore General Hospital,
Visiting Senior Consultant, Division of Surgical Oncology, National Cancer Centre,
Clinical Senior Lecturer, National University of Singapore
