Colorectal cancer

What is colorectal cancer?

The rectum and the colon make up the large intestine, or large bowel. The rectum is the last six inches of the large bowel and connects the colon to the anus. Cancer of the rectum and/or colon is referred to as colorectal cancer and is the fourth most common cancer in the United States. The two cancers are grouped together because they share many characteristics and are treated similarly. About one-third of the 145,000 cases of colorectal cancers diagnosed each year are found in the rectum.

Rectal cancer occurs when cells in the rectum mutate and grow out of control. The disease may also develop when growths, called polyps, on the inner wall of the rectum develop and become cancerous.

The risk of rectal cancer increases with age. The average age of a person diagnosed with colorectal cancer is 68. Men have a higher risk than women. The risk of rectal cancer may be reduced, and the disease may be prevented or caught early, with regular examinations and lifestyle changes, such as:

Exercising
Eating less red and processed meat and more fiber and vegetables
Quitting smoking
Reducing alcohol use

Worldwide, colorectal cancer is the second most common cancer in females and the third most common cancer in males.

What are the causes of colorectal cancer?

Rectal cancer occurs when healthy cells in the rectum develop errors in their DNA. In most cases, the cause of these errors is unknown.

Healthy cells grow and divide in an orderly way to keep your body functioning normally. But when a cell’s DNA is damaged and becomes cancerous, cells continue to divide even when new cells aren’t needed. As the cells accumulate, they form a tumor.

With time, the cancer cells can grow to invade and destroy normal tissue nearby. And cancerous cells can travel to other parts of the body.

Inherited gene mutations that increase the risk of colon and rectal cancer

In some families, gene mutations passed from parents to children increase the risk of colorectal cancer. These mutations are involved in only a small percentage of rectal cancers. Some genes linked to rectal cancer increase an individual’s risk of developing the disease, but they don’t make it inevitable.

Two well-defined genetic colorectal cancer syndromes are:

Hereditary nonpolyposis colorectal cancer (HNPCC). HNPCC, also called Lynch syndrome, increases the risk of colon cancer and other cancers. People with HNPCC tend to develop colon cancer before age 50.
Familial adenomatous polyposis (FAP). FAP is a rare disorder that causes you to develop thousands of polyps in the lining of your colon and rectum. People with untreated FAP have a greatly increased risk of developing colon or rectal cancer before age 40.

FAP, HNPCC and other, rarer inherited colorectal cancer syndromes can be detected through genetic testing. If you’re concerned about your family’s history of colon cancer, talk to your doctor about whether your family history suggests you have a risk of these conditions.

What are the risk factors of colorectal cancer?

The characteristics and lifestyle factors that increase your risk of rectal cancer are the same as those that increase your risk of colon cancer. They include:

Older age. The great majority of people diagnosed with colon and rectal cancer are older than 50. Colorectal cancer can occur in younger people, but it occurs much less frequently.
African-American descent. People of African ancestry born in the United States have a greater risk of colorectal cancer than do people of European ancestry.
A personal history of colorectal cancer or polyps. If you’ve already had rectal cancer, colon cancer or adenomatous polyps, you have a greater risk of colorectal cancer in the future.
Inflammatory bowel disease. Chronic inflammatory diseases of the colon and rectum, such as ulcerative colitis and Crohn’s disease, increase your risk of colorectal cancer.
Inherited syndromes that increase colorectal cancer risk. Genetic syndromes passed through generations of your family can increase your risk of colorectal cancer. These syndromes include FAP and HNPCC.
Family history of colorectal cancer. You’re more likely to develop colorectal cancer if you have a parent, sibling or child with the disease. If more than one family member has colon cancer or rectal cancer, your risk is even greater.
Dietary factors. Colorectal cancer may be associated with a diet low in vegetables and high in red meat, particularly when the meat is charred or well-done.
A sedentary lifestyle. If you’re inactive, you’re more likely to develop colorectal cancer. Getting regular physical activity may reduce your risk of colon cancer.
Diabetes. People with poorly controlled type 2 diabetes and insulin resistance may have an increased risk of colorectal cancer.
Obesity. People who are obese have an increased risk of colorectal cancer and an increased risk of dying of colon or rectal cancer when compared with people considered normal weight.
Smoking. People who smoke may have an increased risk of colon cancer.
Alcohol. Regularly drinking more than three alcoholic beverages a week may increase your risk of colorectal cancer.
Radiation therapy for previous cancer. Radiation therapy directed at the abdomen to treat previous cancers may increase the risk of colorectal cancer.

How to diagnose colorectal cancer?

Tests used to diagnose rectal cancer include the following:

Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
Digital rectal exam (DRE): An exam of the rectum. The doctor or nurse inserts a lubricated, gloved finger into the lower part of the rectum to feel for lumps or anything else that seems unusual. In women, the vagina may also be examined.
Colonoscopy: A procedure to look inside the rectum and colon for polyps (small pieces of bulging tissue), abnormal areas, or cancer. A colonoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove polyps or tissue samples, which are checked under a microscope for signs of cancer.
- Biopsy: The removal of cells or tissues so they can be viewed under a microscope to check for signs of cancer. Tumor tissue that is removed during the biopsy may be checked to see if the patient is likely to have the gene mutation that causes HNPCC. This may help to plan treatment. The following tests may be used:
  Reverse transcription–polymerase chain reaction (RT–PCR) test: A laboratory test in which the amount of a genetic substance called mRNA made by a specific gene is measured. An enzyme called reverse transcriptase is used to convert a specific piece of RNA into a matching piece of DNA, which can be amplified (made in large numbers) by another enzyme called DNA polymerase. The amplified DNA copies help tell whether a specific mRNA is being made by a gene. RT–PCR can be used to check the activation of certain genes that may indicate the presence of cancer cells. This test may be used to look for certain changes in a gene or chromosome, which may help diagnose cancer.
  Immunohistochemistry: A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test is used to help diagnose cancer and to help tell one type of cancer from another type of cancer.
- Carcinoembryonic antigen (CEA) assay: A test that measures the level of CEA in the blood. CEA is released into the bloodstream from both cancer cells and normal cells. When found in higher than normal amounts, it can be a sign of rectal cancer or other conditions.
  The prognosis (chance of recovery) and treatment options depend on the following:
  The stage of the cancer (whether it affects the inner lining of the rectum only, involves the whole rectum, or has spread to lymph nodes, nearby organs, or other places in the body).
  Whether the tumor has spread into or through the bowel wall.
  Where the cancer is found in the rectum.
  Whether the bowel is blocked or has a hole in it.
  Whether all of the tumor can be removed by surgery.
  The patient’s general health.
  Whether the cancer has just been diagnosed or has recurred (come back).

What are the stages of colorectal cancer?

After rectal cancer has been diagnosed, tests are done to find out if cancer cells have spread within the rectum or to other parts of the body.
There are three ways that cancer spreads in the body.
Cancer may spread from where it began to other parts of the body.
The following stages are used for rectal cancer:
- Stage 0 (Carcinoma in Situ)
- Stage I
- Stage II
- Stage III
- Stage IV

After rectal cancer has been diagnosed, tests are done to find out if cancer cells have spread within the rectum or to other parts of the body.

The process used to find out whether cancer has spread within the rectum or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment.

The following tests and procedures may be used in the staging process:

Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
Colonoscopy: A procedure to look inside the rectum and colon for polyps (small pieces of bulging tissue). abnormal areas, or cancer. A colonoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove polyps or tissue samples, which are checked under a microscope for signs of cancer.

CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the abdomen, pelvis, or chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
PET scan (positron emission tomography scan): A procedure to find malignant tumor cells in the body. A small amount of radioactive glucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
Endorectal ultrasound: A procedure used to examine the rectum and nearby organs. An ultrasound transducer (probe) is inserted into the rectum and used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram. The doctor can identify tumors by looking at the sonogram. This procedure is also called transrectal ultrasound.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

Tissue. The cancer spreads from where it began by growing into nearby areas.
Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if rectal cancer spreads to the lung, the cancer cells in the lung are actually rectal cancer cells. The disease is metastatic rectal cancer, not lung cancer.

The following stages are used for rectal cancer:

Stage 0 (Carcinoma in Situ)

In stage 0 rectal cancer, abnormal cells are found in the mucosa (innermost layer) of the rectum wall. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Stage I colorectal cancer

In stage I rectal cancer, cancer has formed in the mucosa (innermost layer) of the rectum wall and has spread to the submucosa (layer of tissue next to the mucosa) or to the muscle layer of the rectum wall.

Stage II colorectal cancer

Stage II rectal cancer is divided into stages IIA, IIB, and IIC.

Stage IIA: Cancer has spread through the muscle layer of the rectum wall to the serosa (outermost layer) of the rectum wall.
Stage IIB: Cancer has spread through the serosa (outermost layer) of the rectum wall to the tissue that lines the organs in the abdomen (visceral peritoneum).
Stage IIC: Cancer has spread through the serosa (outermost layer) of the rectum wall to nearby organs.

Stage III colorectal cancer

Stage III rectal cancer is divided into stages IIIA, IIIB, and IIIC.

In stage IIIA, cancer has spread:

through the mucosa (innermost layer) of the rectum wall to the submucosa (layer of tissue next to the mucosa) or to the muscle layer of the rectum wall. Cancer has spread to one to three nearby lymph nodes or cancer cells have formed in tissue near the lymph nodes; or
through the mucosa (innermost layer) of the rectum wall to the submucosa (layer of tissue next to the mucosa). Cancer has spread to four to six nearby lymph nodes.

In stage IIIB, cancer has spread:

through the muscle layer of the rectum wall to the serosa (outermost layer) of the rectum wall or has spread through the serosa to the tissue that lines the organs in the abdomen (visceral peritoneum). Cancer has spread to one to three nearby lymph nodes or cancer cells have formed in tissue near the lymph nodes; or
to the muscle layer or to the serosa (outermost layer) of the rectum wall. Cancer has spread to four to six nearby lymph nodes; or
through the mucosa (innermost layer) of the rectum wall to the submucosa (layer of tissue next to the mucosa) or to the muscle layer of the rectum wall. Cancer has spread to seven or more nearby lymph nodes.

In stage IIIC, cancer has spread:

through the serosa (outermost layer) of the rectum wall to the tissue that lines the organs in the abdomen (visceral peritoneum). Cancer has spread to four to six nearby lymph nodes; or
through the muscle layer of the rectum wall to the serosa (outermost layer) of the rectum wall or has spread through the serosa to the tissue that lines the organs in the abdomen (visceral peritoneum). Cancer has spread to seven or more nearby lymph nodes; or
through the serosa (outermost layer) of the rectum wall to nearby organs. Cancer has spread to one or more nearby lymph nodes or cancer cells have formed in tissue near the lymph nodes.

Stage IV colorectal cancer

Stage IV rectal cancer is divided into stages IVA, IVB, and IVC.

Stage IVA: Cancer has spread to one area or organ that is not near the rectum, such as the liver, lung, ovary, or a distant lymph node.
Stage IVB: Cancer has spread to more than one area or organ that is not near the rectum, such as the liver, lung, ovary, or a distant lymph node.
Stage IVC: Cancer has spread to the tissue that lines the wall of the abdomen and may have spread to other areas or organs.

Recurrent Rectal Cancer

Recurrent rectal cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the rectum or in other parts of the body, such as the colon, pelvis, liver, or lungs.

How is colorectal cancer treated?

There are different types of treatment for patients with rectal cancer.
Six types of standard treatment are used:
- Surgery
- Radiation therapy
- Chemotherapy
- Active surveillance
- Targeted therapy
- Immunotherapy
Other types of treatment are being tested in clinical trials.
Treatment for rectal cancer may cause side effects.
Patients may want to think about taking part in a clinical trial.
Patients can enter clinical trials before, during, or after starting their cancer treatment.
Follow-up tests may be needed.

There are different types of treatment for patients with colorectal cancer.

Different types of treatment are available for patients with rectal cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Six types of standard treatment are used:

Surgery in colorectal cancer

Surgery is the most common treatment for all stages of rectal cancer. The cancer is removed using one of the following types of surgery:

Polypectomy: If the cancer is found in a polyp (a small piece of bulging tissue), the polyp is often removed during a colonoscopy.
Local excision: If the cancer is found on the inside surface of the rectum and has not spread into the wall of the rectum, the cancer and a small amount of surrounding healthy tissue is removed.
Resection: If the cancer has spread into the wall of the rectum, the section of the rectum with cancer and nearby healthy tissue is removed. Sometimes the tissue between the rectum and the abdominal wall is also removed. The lymph nodes near the rectum are removed and checked under a microscope for signs of cancer.
Radiofrequency ablation: The use of a special probe with tiny electrodes that kill cancer cells. Sometimes the probe is inserted directly through the skin and only local anesthesia is needed. In other cases, the probe is inserted through an incision in the abdomen. This is done in the hospital with general anesthesia.
Cryosurgery: A treatment that uses an instrument to freeze and destroy abnormal tissue. This type of treatment is also called cryotherapy.
Pelvic exenteration: If the cancer has spread to other organs near the rectum, the lower colon, rectum, and bladder are removed. In women, the cervix, vagina, ovaries, and nearby lymph nodes may be removed. In men, the prostate may be removed. Artificial openings (stoma) are made for urine and stool to flow from the body to a collection bag.

After the cancer is removed, the surgeon will either:

do an anastomosis (sew the healthy parts of the rectum together, sew the remaining rectum to the colon, or sew the colon to the anus);

or
make a stoma (an opening) from the rectum to the outside of the body for waste to pass through. This procedure is done if the cancer is too close to the anus and is called a colostomy. A bag is placed around the stoma to collect the waste. Sometimes the colostomy is needed only until the rectum has healed, and then it can be reversed. If the entire rectum is removed, however, the colostomy may be permanent.

Radiation therapy and/or chemotherapy may be given before surgery to shrink the tumor, make it easier to remove the cancer, and help with bowel control after surgery. Treatment given before surgery is called neoadjuvant therapy. After all the cancer that can be seen at the time of the surgery is removed, some patients may be given radiation therapy and/or chemotherapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy in colorectal cancer

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy:

External radiation therapy uses a machine outside the body to send radiation toward the cancer.
Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer.

The way the radiation therapy is given depends on the type and stage of the cancer being treated. External radiation therapy is used to treat rectal cancer.

Short-course preoperative radiation therapy is used in some types of rectal cancer. This treatment uses fewer and lower doses of radiation than standard treatment, followed by surgery several days after the last dose.

Chemotherapy in colorectal cancer

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly in the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy).

Chemoembolization of the hepatic artery is a type of regional chemotherapy that may be used to treat cancer that has spread to the liver. This is done by blocking the hepatic artery (the main artery that supplies blood to the liver) and injecting anticancer drugs between the blockage and the liver. The liver’s arteries then carry the drugs into the liver. Only a small amount of the drug reaches other parts of the body. The blockage may be temporary or permanent, depending on what is used to block the artery. The liver continues to receive some blood from the hepatic portal vein, which carries blood from the stomach and intestine.

The way the chemotherapy is given depends on the type and stage of the cancer being treated.

See Drugs Approved for Colon and Rectal Cancer for more information.

Active surveillance

Active surveillance is closely following a patient’s condition without giving any treatment unless there are changes in test results. It is used to find early signs that the condition is getting worse. In active surveillance, patients are given certain exams and tests to check if the cancer is growing. When the cancer begins to grow, treatment is given to cure the cancer. Tests include the following:

Digital rectal exam.
MRI.
Endoscopy.
Sigmoidoscopy.
CT scan.
Carcinoembryonic antigen (CEA) assay.

Targeted therapy in colorectal cancer

Targeted therapy is a type of treatment that uses drugs or other substances to identify and attack specific cancer cells without harming normal cells.

Types of targeted therapies used in the treatment of rectal cancer include the following:

Monoclonal antibodies: Monoclonal antibody therapy is a type of targeted therapy being used for the treatment of rectal cancer. Monoclonal antibody therapy uses antibodies made in the laboratory from a single type of immune system cell. These antibodies can identify substances on cancer cells or normal substances that may help cancer cells grow. The antibodies attach to the substances and kill the cancer cells, block their growth, or keep them from spreading. Monoclonal antibodies are given by infusion. They may be used alone or to carry drugs, toxins, or radioactive material directly to cancer cells.
There are different types of monoclonal antibody therapy:
- Vascular endothelial growth factor (VEGF) inhibitor therapy: Cancer cells make a substance called VEGF, which causes new blood vessels to form (angiogenesis) and helps the cancer grow. VEGF inhibitors block VEGF and stop new blood vessels from forming. This may kill cancer cells because they need new blood vessels to grow. Bevacizumab and ramucirumab are VEGF inhibitors and angiogenesis inhibitors.
- Epidermal growth factor receptor (EGFR) inhibitor therapy: EGFRs are proteins found on the surface of certain cells, including cancer cells. Epidermal growth factor attaches to the EGFR on the surface of the cell and causes the cells to grow and divide. EGFR inhibitors block the receptor and stop the epidermal growth factor from attaching to the cancer cell. This stops the cancer cell from growing and dividing. Cetuximab and panitumumab are EGFR inhibitors.
Angiogenesis inhibitors: Angiogenesis inhibitors stop the growth of new blood vessels that tumors need to grow.
- Ziv-aflibercept is a vascular endothelial growth factor trap that blocks an enzyme needed for the growth of new blood vessels in tumors.
- Regorafenib is used to treat colorectal cancer that has spread to other parts of the body and has not gotten better with other treatment. It blocks the action of certain proteins, including vascular endothelial growth factor. This may help keep cancer cells from growing and may kill them. It may also prevent the growth of new blood vessels that tumors need to grow.

Immunotherapy in colorectal cancer

Immunotherapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or biologic therapy.

Immune checkpoint inhibitor therapy is a type of immunotherapy:

Immune checkpoint inhibitor therapy: PD-1 is a protein on the surface of T-cells that helps keep the body’s immune responses in check. When PD-1 attaches to another protein called PDL-1 on a cancer cell, it stops the T cell from killing the cancer cell. PD-1 inhibitors attach to PDL-1 and allow the T cells to kill cancer cells. Pembrolizumab is a type of immune checkpoint inhibitor.