COLORECTAL CANCER
 

The colon and rectum are part of the digestive tract which is located in the abdomen between the small intestine and the anus. Cancer that originates in the colon or rectum is called colorectal cancer.

The colon absorbs water and salts from food and transports them into the bloodstream. It is about 6 feet in length and consists of several parts: the caecum, the ascending colon, the transverse colon, the descending colon, and the sigmoid colon.

The rectum is the last segment of the large intestine. It is 8 to 10 inches in length and leads to the anus, which is the opening to the outside of the body where faeces is eliminated from the body.

Over 95% of colorectal cancers are adenocarcinomas that develop when the lining cells undergo genetic change. The disease often begins as a polyp which can gradually become cancerous.
 

Incidence
Incidence of colorectal cancer is highest in developed countries such as the United States and Japan, and lowest in developing countries in Africa. In Singapore, it is the most common cancer type overall. It is the third most common type of cancer in both men and women in the United States.

The death rate from colorectal cancer has declined over the past 15 years due to improved screening methods and advances in treatment.

Cause and Risk Factors

The cause of colorectal cancer is unknown. Age is the primary risk factor. Incidence of the disease increases significantly after the age of 50.

Some people have a genetic predisposition to developing colorectal cancer. When this predisposition is combined with a high dietary intake of fat and red meat and a low dietary intake of fibre, vitamins, and minerals, the risk is even higher.

Lifestyle factors that increase the risk include the following:

• Daily alcohol use (may double the risk)
• Eating a high-fat, low-fibre diet
• Obesity
• Sedentary lifestyle
• Smoking

A family history of intestinal polyps or colorectal cancer (especially before the age of 60) results in an increased risk for the disease. Other diseases and medical conditions that increase the risk include the following:

• Diabetes
• Genetic disorders such as familial polyposis syndromes and hereditary non-polyposis colon cancer syndrome (HNPCC)
• Inflammatory bowel disease (e.g., ulcerative colitis, Crohn's colitis, granulomatous colitis)
• Personal history of intestinal polyps or colorectal cancer

Hereditary nonpolyposis colon cancer (HNPCC) syndrome is a genetic condition characterized by early-onset colorectal cancer (i.e. develops before age 50) and multiple colorectal cancers. This syndrome also may be associated with other cancers (e.g., cancer of the small intestine, uterus, stomach, and renal pelvis).

The following criteria (called Amsterdam criteria) are used to identify patients at risk for this condition:

• At least three family members with HNPCC-associated cancer (e.g. cancer of the colon, rectum, uterus, small intestine, renal pelvis)
• At least one of these family members must be a first-degree relative of the other two
• At least two successive generations affected
• At least one family member diagnosed before age 50

Signs and Symptoms

Colorectal cancer can be asymptomatic. Blood in the stool is a common sign of the disease. Blood may be bright red or dark in colour, and may not be noticeable. Chronic bleeding may result in iron deficiency anaemia, which may cause fatigue and pale skin.

Other symptoms include the following:

• Abdominal discomfort such as pain, bloating, cramping, feeling of fullness
• Change in bowel habits
• Constipation or diarrhoea
• Narrow stools
• Nausea and vomiting
• Weight loss

Screening

Screening is recommended beginning at age 50 and includes the following:

• Digital rectal examination (DRE) and stool occult blood test annually and
• Double-contrast barium enema every 5 - 10 years and
• Flexible sigmoidoscopy every 5 years, or
• Total colonoscopy every 5 - 10 years

Diagnosis of colorectal cancer in symptomatic patients and high-risk patients includes laboratory and imaging tests. Biopsy (i.e., removal of a tissue sample for examination under a microscope) is necessary to confirm the diagnosis.

When colorectal cancer is suspected, laboratory tests such as urinalysis, blood tests (e.g., carcinoembryonic antigen level, complete blood count, electrolyte and chemical panels), and other imaging tests such as chest X ray and CT scans are performed.

Imaging Tests

Imaging tests include the following:

• Chest x-ray (used to detect cancer that has spread to the lungs)
• CT scans (computerized tomography) (used to detect metastasis to lymph nodes, liver, or lungs)
• Double-contrast barium enema (used to detect tumours throughout the colon)
• Total colonoscopy (used to detect tumours throughout the colon). The advantage of this method is to enable a biopsy of the tumour to be taken

Treatment

Surgery is the treatment of choice for colorectal cancer. Treatment depends on the stage of the disease and the overall health of the patient. Chemotherapy and radiation therapy is often used as adjuvant treatment (i.e. in addition to surgery).

Surgery
Surgical resection of the bowel is used to treat the majority of colorectal cancer patients. This procedure may be performed through a large incision in the abdomen (called open surgery) or through several small incisions (called laparoscopic surgery).

Chemotherapy
Chemotherapy is a systemic treatment (travels throughout the body via the bloodstream) that often uses a combination of drugs to slow tumour growth and destroy cancer cells. Drugs may be administered orally or intravenously.

Chemotherapy is often used as a first-line treatment for advanced colorectal cancer to destroy cancer cells that have spread. It also may be used prior to surgery (called neoadjuvant therapy) to shrink the tumor, may be administered following surgery (called adjuvant therapy), and may be combined with biological therapy and radiation therapy.

Newer combinations of chemotherapy drugs, such as FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) and FOFIRI (5-fluorouracil, leucovorin, and irinotecan) may be used to prevent recurrence following surgery or to shrink the tumour prior to surgery.

In addition to chemotherapy drugs, new biological agents (also called targeted therapies) such as Cetuximab (Erbitux) may also be used to treat advanced colorectal cancer. These drugs prevent cancer cell receptors from receiving factors (e.g., epidermal growth factor) that cause cell growth, cell division, and additional metastasis.

Bevacizumab (Avastin) may also be used to treat advanced colorectal cancer. This medication prevents new blood vessels, which are necessary for tumour growth, from forming. It does not affect normal tissues that already have an established blood supply.

These biological agents target specific cells so they usually do not cause systemic side effects.

Radiation Therapy

Radiation therapy uses high energy x-rays to destroy cancer cells and shrink tumours. It may be used in addition to surgery to treat colorectal cancer (called adjuvant therapy). It also may be used to relieve symptoms (called palliative treatment) in patients with advanced colorectal cancer.

Follow-up Treatment

Follow-up care is recommended for colorectal cancer patients to ensure that recurrent or advanced disease is detected as soon as possible. Patients should undergo regular physical examinations, faecal occult blood tests, colonoscopies, CT scans, and chest x-rays.

Prevention

Early detection and removal of intestinal polyps may help prevent colorectal cancer. Studies are being conducted to determine if reducing risk factors (e.g., smoking, daily alcohol consumption), eating a low-fat, high-fibre diet, and increasing physical activity can help prevent the disease.