Colorectal Cancer

 Statistics 

Estimated numbers (thousands) Men Women Both sexes
Cases Deaths 5-year prev. Cases Deaths 5-year prev. Cases Deaths 5-year prev.
India 37 28 50 27 21 37 64 49 87

 

Globocan, 2012

The incidence of rectal cancer in India is lower than that in the western countries, and it is the tenth leading cancer in India [1]

Mean age of rectal cancer (RC): around 40-45 yr.

Risk Factors 

  • Risk factors you cannot change (non-modifiable risk factors)
    • Age: Your risk gets higher as you get older. Younger adults may also develop colorectal cancer but the chances increase markedly after you turn 50.
    • Personal history of colorectal polyps or colorectal cancer: If you have a history of certain types of polyps known as adenomatous polyps (adenomas), you are at increased risk of developing colorectal cancer. This is especially true if the polyps are large or if they are more in number.

    If you have had colorectal cancer earlier, you are more prone to develop new cancers in other areas of the colon and rectum even if the previous cancer was completely removed. The chances are greater if you had your first colorectal cancer at a younger age.

    • A personal history of inflammatory bowel disease (IBD): Having a history of ulcerative colitis or Crohn’s disease ( types of inflammatory bowel diseases) increases the risk of developing colorectal cancer.  If you have IBD, you may need to start being screened  regularlyfor colorectal cancer from a younger age.
    • Family history of colorectal cancer: People with a history of colorectal cancer in a first-degree relative (parent, sibling, or child) are at increased risk. The risk is even higher if that relative developed cancer at an age younger than 45, or if more than one first-degree relative is affected.
    • Race or ethnic background: being African American or Ashkenazi increases the risk.
    • Inherited syndromes that increase colon cancer risk.Certain genetic syndromes passed through generations of your family can increase your risk of colon cancer. These syndromes include familial adenomatous polyposis and hereditary nonpolyposis colorectal cancer (also known as Lynch syndrome).

    Risk factors you can change (Modifiable risk factors)

    • Obesity. People who are obese have an increased risk of colon cancer and an increased risk of dying of colon cancer.
    • Smoking. People who have smokedcigarettes  for a long time are more likely to develop and die from colorectal cancer.
    • Type 2 diabetes: People with diabetes and insulin resistance may have an increased risk of colon cancer.
    • Alcohol. Heavy use of alcohol may increase your risk of colon cancer
    • Sedentary lifestyle. If you are inactive, you  are more likely to develop colon cancer. Getting regular physical activity may reduce your risk of colon cancer.
    • Certain types of diets: Diet rich in red meats and processed meats  can increase risk for colorectal cancer.

    Cooking meats at very high heat (frying, broiling, or grilling) can create chemicals that might increase cancer risk. Diets high in vegetables, fruits, and whole grains have been linked with a lower risk of colorectal cancer, but fiber supplements have not been shown to help.

    • Radiation therapy for cancer. Radiation therapy directed at the abdomen to treat previous cancers may increase the risk of colon cancer.

Signs and Symptoms 

  • Changes in bowel habits, including persistent constipation or diarrhea, a feeling of not being able to empty the bowel completely, an urgency to move the bowels, or a change in the consistency of the stools ( long, thin “pencil stools”)
  • Rectal bleeding or dark patches of blood in or on stool
  • Persistent abdominal discomfort such as cramps, bloating, gas or pain
  • Unexplained fatigue, weakness, loss of appetite and/or weight loss
  • Pelvic pain, which occurs at later stages of the disease

Most people with colorectal cancer do not experience any symptoms or have only non-specific symptoms in the early stages. When the symptoms appear, they vary depending upon the size and location of tumor in the intestine.

 Screening and Diagnosis

Screening for Colorectal Cancer

Regular screening can help in early detection of colorectal cancer, when it is likely to be curable. In addition, some polyps can be detected and removed before they turn into colorectal cancer.

The various tests recommended to be used in screening for colorectal cancer include:

  • Faecal occult blood test (FOBT) using guaiac-based test or immunochemical test: Stool sample is tested for presence of blood, which may come from a polyp or cancer
  • Flexible sigmoidoscopy: A flexible tube with light source at the end is inserted into the rectum and lower colon to look for polyps or cancer
  • Colonoscopy: A longer flexible tube is inserted to examine the entire colon up to the rectum for any polyps or growth
  • CT colonography: This is a special type of CT scan of the colon and rectum to look for small polyps

Screening is recommended for high-risk individuals, i.e. those with a close relative having colorectal cancer or polyps or patients having inflammatory bowel disease or patients with an inherited syndrome that increase the risk of colorectal cancer. FOBT should be done every 1-2 years, flexible sigmoidoscopy every 5 years and colonoscopy every 10 years in high-risk individuals.

Diagnosis of Colorectal Cancer

The symptoms of colorectal cancer usually appear only with advanced disease. If your doctor finds something suspicious in screening or you have any of the symptoms of colorectal cancer, further tests will be required to diagnose the condition.

History & Physical Examination:

In case you have any of the signs or symptoms suggesting colorectal cancer, the doctor will take complete medical history for presence of risk factors, including your family history.

During general physical examination, the doctor will palpate your abdomen for palpable masses or enlarged organs. A digital rectal examination (DRE) may also be performed. In this test, a gloved and lubricated finger is inserted into the rectum to feel for any abnormal areas.

Blood tests:

  • Hemogram to check for anemia, since some patients with colorectal cancer have chronic blood loss and become anemic.
  • Liver enzymes may be checked since colorectal cancer often spread to liver.
  • Serum tumor markers: Tumor cells secrete certain substances called tumor markers that can be tested in blood for establishing the diagnosis. For colorectal cancer, the most common tumor markers tested include Carcinoembryonic antigen (CEA) and CA 19-9. These tests can be used for diagnosis along with other investigations as well as to monitor patients after treatment for colorectal cancer.

These tumor markers cannot be used for screening of colorectal cancer because elevation of their levels doesn’t tell for sure that the person has cancer. The levels of these markers can sometimes be raised in benign conditions as well.

Colonoscopy:

This is the most commonly used test to diagnose colorectal cancer if the symptoms are highly suggestive. It allows the doctor to look at the entire length of the colon and rectum using a colonoscope which is a thin flexible lighted tube with camera at the end attached to a monitor on the doctor’s desk. It is inserted through the anus and the camera allows the doctor to closely examine the inside of the colon through the images on the monitor. The colonoscope can also be used to insert special instruments to take a biopsy of suspicious-looking area or to remove polyps.

The test can be done on an outpatient basis in a hospital or doctor’s clinic. Before the test, certain instructions are given to make colon and rectum empty of food residue by a laxative and/or enema. These instructions should be understood well and followed perfectly. Colonoscopy is generally performed under mild sedation. The procedure is quite safe, though uncomfortable. Sometimes, you may have bloating, gas pains or cramping since air is pumped into the colon for better visualization. If a biopsy has been taken or polyp removed, you may have blood in stool for 1-2 days after the test.

Biopsy:

Tissue biopsy is taken during colonoscopy from any suspicious area. A small piece of tissue is removed with a special instrument passed through the scope. The sample is sent to pathology lab for testing by a pathologist who looks for cancer cells in the specimen.

Genetic tests may also be done on the biopsy specimens to identify specific gene changes in the cancer cells. These tests are available at very few centres in the country.

Imaging Tests:

  • Computed tomography (CT) scan can help to find out if the colorectal cancer has spread to liver and other organs. A biopsy from liver may also be taken while CT scan is being done to confirm if a nodule in liver is due to spread of cancer.
  • Ultrasound: Endorectal USG, in which a special transducer is inserted into the rectum, can help to see how far the cancer has penetrated the rectal wall.
  • Magnetic resonance imaging (MRI) can help to look for local spread of colorectal cancer so that treatment can be planned accordingly.
  • Chest X-ray is done to look for spread of cancer to lungs and to look for any co-morbid condition before surgery.

Stages of Colorectal Cancer

Stage 0 or Carcinoma in situ: Abnormal cells are found in the innermost lining of the colon or rectal wall (mucosa).

Stage I: In this stage, cancer has formed in the mucosa (innermost layer) and has spread to the submucosa (layer of tissue under the mucosa) and muscle layer of colon or rectum. It has not spread into nearby tissue or lymph nodes

Stage II:  The cancer has grown through the wall of the colon or rectum to the lining of the abdomen, called the visceral peritoneum and has grown into nearby structures. It has not spread to the nearby lymph nodes or elsewhere.

Stage III:  The cancer has grown through the inner lining or into the muscle layers of the intestine and spread to lymph nodes, but not to other distant parts of the body

Stage IV: The cancer has spread to a distant part of the body, such as the liver or lungs.

Treatment of Colorectal cancer

Different modalities to treat colorectal cancer include:

  • Surgery
  • Radiotherapy
  • Chemotherapy
  • Targeted therapy

These are used alone or in combination depending on the stage of the cancer, performance status of the patient, grade of the tumor and other factors.

Stage-wise treatment of colorectal cancer:

Treatment of colorectal cancer depends on the stage of the cancer.

Stage 0 colon/rectal cancer

Removal of a polyp which is called polypectomy, during the colonoscopy procedure is the treatment at this stage. If the polyp is not excised completely, additional surgery may be required. Rarely removing a part of the colon which is called partial colectomy may be required if a tumor is too big to be removed by local excision.

Stage I colon/rectal cancer

Surgical removal of the tumor and lymph nodes is usually the only treatment needed.

Partial colectomy- surgery to remove the section of colon that has cancer and nearby lymph nodes is the standard treatment. Additional treatment is usually not required.

Stage II colon/rectal cancer

Partial colectomy -surgery to remove the section of colon that has cancer and nearby lymph nodes is the standard treatment. Additional treatment in the form of chemotherapy or radiotherapy is indicated in certain conditions like: high grade tumor, high CEA (carcinoembryonic antigen) levels >5 ng/ml, if fewer than 12 lymph nodes are removed and examined and if the tumor had caused obstruction or perforation of the colon before surgery.

The various chemotherapy regimens used in treatment of colorectal cancer are given below.

Stage III colon/rectal cancer

Treatment usually involves surgical removal of the tumor followed by adjuvant chemotherapy. Patients with rectal cancer, radiation therapy may be used along with chemotherapy before or after surgery along with adjuvant chemotherapy.

Stage IV colon cancer

In this stage, surgery is not possible in majority of the cases considering the metastasis of the disease.  However if the size of the metastasis is small and is excisable, surgery may be planned in such cases at the discretion of the surgeon.

Operations such as diverting colostomy may be required in patients with obstructed colon or perforated colon. In this procedure, the colon is cut above the level of the cancer and the end is attached to an opening in the skin on the abdomen to allow waste out.

CHEMOTHERAPY REGIMENS USED IN COLORECTAL CANCER

Some common treatment regimens include:

  • 5-Flurouracil (5-FU)
  • 5-FU with leucovorin
  • Capecitabine which is an oral form of 5-FU
  • 5-FU with leucovorin and oxaliplatin (FOLFOX)
  • 5-FU with leucovorin and irinotecan (FOLFIRI)
  • Irinotecan alone
  • Capecitabine with either irinotecan or oxaliplatin
  • Any of the above with either cetuximab, bevacizumab, or panitumumab
  • FOLFIRI with ziv-aflibercept or ramucirumab
  • Regorafenib alone

TARGETED THERAPY IN THE TREATMENT OF COLORECTAL CANCER

Targeted therapy targets the cancer’s specific genes, proteins, or the tissue environment that contributes to cancer growth and survival. Targeted therapy blocks the growth and spread of cancer cells while limiting damage to healthy cells.

Types of targeted therapy

Anti-angiogenesis therapy.

It acts by stopping angiogenesis, which is the process of making new blood vessels. Few examples in this group include Bevacizumab, Ziv-aflibercept, Ramucirumab etc.

  • Epidermal growth factor receptor (EGFR) inhibitors.

It acts by inhibiting the epidermal growth factor receptor. This may be effective for stopping or slowing the growth of colorectal cancer. Cetuximab, Panitumumab belong to this group of targeted therapy.

References 

[1] Three-years report of Population Based Cancer Registries 2006-2008 (Detailed Tabulations of Individual Registries Data). National Cancer Registry Programme (Indian Council of Medical Research), Bangalore November 2010. Available from: http://www.PBCR_2006_2008.aspx, (accessed on December 27, 2012)