Rectal Cancer Treatment

• Rectal cancer is a disease in which malignant (cancer) cells form in the tissues of the rectum.
• Health history affects the risk of developing rectal cancer.
• Signs of rectal cancer include a change in bowel habits or blood in the stool.
• Tests that examine the rectum and colon are used to detect (find) and diagnose rectal cancer.
• Certain factors affect prognosis (chance of recovery) and treatment options.

Rectal cancer is a disease in which malignant (cancer) cells form in the tissues of the rectum.

The rectum is part of the body’s digestive system. The digestive system takes in nutrients (vitamins, minerals, carbohydrates, fats, proteins, and water) from foods and helps pass waste material out of the body. The digestive system is made up of the esophagus, stomach, and the small and large intestines. The colon (large bowel) is the first part of the large intestine and is about 5 feet long. Together, the rectum and anal canal make up the last part of the large intestine and are 6-8 inches long. The anal canal ends at the anus (the opening of the large intestine to the outside of the body).

Health history affects the risk of developing rectal cancer. Anything that increases your chance of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn’t mean that you will not get cancer. Talk to your doctor if you think you may be at risk for colorectal cancer.

Risk factors for colorectal cancer include the following:

• Having a family history of colon or rectal cancer in a first-degree relative (parent, sibling, or child).
• Having a personal history of cancer of the colon, rectum, or ovary.
• Having a personal history of high-risk adenomas (colorectal polyps that are 1 centimeter or larger in size or that have cells that look abnormal under a microscope).
• Having inherited changes in certain genes that increase the risk of familial adenomatous polyposis (FAP) or Lynch syndrome (hereditary nonpolyposis colorectal cancer).
• Having a personal history of chronic ulcerative colitis or Crohn disease for 8 years or more.
• Having three or more alcoholic drinks per day.
• Smoking cigarettes.
• Being black.
• Being obese.
• Older age is a main risk factor for most cancers. The chance of getting cancer increases as you get older.

Signs of rectal cancer include a change in bowel habits or blood in the stool. These and other signs and symptoms may be caused by rectal cancer or by other conditions. Check with your doctor if you have any of the following:

• Blood (either bright red or very dark) in the stool.
• A change in bowel habits.
• Diarrhea.
• Constipation.
• Feeling that the bowel does not empty completely.
• Stools that are narrower or have a different shape than usual.
• General abdominal discomfort (frequent gas pains, bloating, fullness, or cramps).
• Change in appetite.
• Weight loss for no known reason.
• Feeling very tired.

Tests that examine the rectum and colon are used to detect (find) and diagnose rectal 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 cells in a sample of tissue are studied using chemicals to look for certain changes in the structure or function of genes.
• Immunohistochemistry: A test that uses antibodies to check for certain antigens in a sample of tissue. The antibody is usually linked to a radioactive substance or a dye that causes the tissue to light up under a microscope. This type of test may be used to tell the difference between different types 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 following stages are used for rectal cancer:

Stage 0 (Carcinoma in Situ)

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

Stage I

In stage I, cancer has formed in the mucosa (innermost layer) of the rectum wall and has spread to the submucosa (layer of tissue under the mucosa). Cancer may have spread to the muscle layer of the rectum wall.

Stage II

Stage II rectal cancer is divided into stage IIA, stage IIB, and stage 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 but has not spread to nearby organs.
• Stage IIC: Cancer has spread through the serosa (outermost layer) of the rectum wall to nearby organs.

Stage III

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

• In stage IIIA:
  • Cancer has spread through the mucosa (innermost layer) of the rectum wall to the submucosa (layer of tissue under the mucosa) and may have spread to the muscle layer of the rectum wall. Cancer has spread to at least one but not more than 3 nearby lymph nodes or cancer cells have formed in tissues near the lymph nodes; or
  • Cancer has spread through the mucosa (innermost layer) of the rectum wall to the submucosa (layer of tissue under the mucosa). Cancer has spread to at least 4 but not more than 6 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 but not to nearby organs. Cancer has spread to at least one but not more than 3 nearby lymph nodes or cancer cells have formed in tissues near the lymph nodes; or
  • Cancer has spread to the muscle layer of the rectum wall or to the serosa (outermost layer) of the rectum wall. Cancer has spread to at least 4 but not more than 6 nearby lymph nodes; or
  • Cancer has spread through the mucosa (innermost layer) of the rectum wall to the submucosa (layer of tissue under the mucosa) and may have spread to the muscle layer of the rectum wall. Cancer has spread to 7 or more nearby lymph nodes.
• In stage IIIC:
  • Cancer has spread through the serosa (outermost layer) of the rectum wall but has not spread to nearby organs. Cancer has spread to at least 4 but not more than 6 nearby lymph nodes; or
  • 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 but has not spread to nearby organs. Cancer has spread to 7 or more nearby lymph nodes; or
  • Cancer has spread through the serosa (outermost layer) of the rectum wall and has spread to nearby organs. Cancer has spread to one or more nearby lymph nodes or cancer cells have formed in tissues near the lymph nodes.

Stage IV

Stage IV rectal cancer is divided into stage IVA and stage IVB.

• Stage IVA: Cancer may have spread through the rectum wall and may have spread to nearby organs or lymph nodes. Cancer has spread to one organ that is not near the rectum, such as the liver, lung, or ovary, or to a distant lymph node.
• Stage IVB: Cancer may have spread through the rectum wall and may have spread to nearby organs or lymph nodes. Cancer has spread to more than one organ that is not near the rectum or into the lining of the abdominal wall.

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.

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.

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.

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.

Five types of standard treatment are used:

Surgery

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. Even if all the cancer that can be seen at the time of the operation 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

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

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.

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

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.
• Bevacizumab and ramucirumab are types of monoclonal antibodies that bind to a protein called vascular endothelial growth factor (VEGF). This may prevent the growth of new blood vessels that tumors need to grow.
• Cetuximab and panitumumab are types of monoclonal antibodies that bind to a protein called epidermal growth factor receptor (EGFR) on the surface of some types of cancer cells. This may stop cancer cells from growing and dividing.
• 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.

Patients may want to think about taking part in a clinical trial. For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better.

There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment. Clinical trials are taking place in many parts of the country.

Follow-up tests may be needed. Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated.

Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

After treatment for rectal cancer, a blood test to measure amounts of carcinoembryonic antigen (a substance in the blood that may be increased when cancer is present) may be done to see if the cancer has come back.

Stage 0 (Carcinoma in Situ)

Treatment of stage 0 may include the following:

• Simple polypectomy.
• Local excision.
• Resection (when the tumor is too large to remove by local excision).

Stage I Rectal Cancer

Treatment of stage I rectal cancer may include the following:

• Local excision.
• Resection.
• Resection with radiation therapy and chemotherapy after surgery.

Stages II and III Rectal Cancer

Treatment of stage II and stage III rectal cancer may include the following:

• Surgery.
• Chemotherapy combined with radiation therapy, followed by surgery.
• Short-course radiation therapy followed by surgery and chemotherapy.
• Resection followed by chemotherapy combined with radiation therapy.
• Chemotherapy combined with radiation therapy, followed by active surveillance. Surgery may be done if the cancer recurs (comes back).
• A clinical trial of a new treatment.

Stage IV and Recurrent Rectal Cancer

Treatment of stage IV and recurrent rectal cancer may include the following:

• Surgery with or without chemotherapy or radiation therapy.
• Systemic chemotherapy with or without targeted therapy (a monoclonal antibody or angiogenesis inhibitor).
• Chemotherapy to control the growth of the tumor.
• Radiation therapy, chemotherapy, or a combination of both, as palliative therapy to relieve symptoms and improve the quality of life.
• Placement of a stent to help keep the rectum open if it is partly blocked by the tumor, as palliative therapy
• to relieve symptoms and improve the quality of life.
• A clinical trial of a new anticancer drug.

Treatment of rectal cancer that has spread to other organs depends on where the cancer has spread. Treatment for areas of cancer that have spread to the liver includes the following:

• Surgery to remove the tumor.
• Chemotherapy may be given before surgery, to shrink the tumor.
• Cryosurgery or radiofrequency ablation.
• Chemoembolization and/or systemic chemotherapy.
• A clinical trial of chemoembolization combined with radiation therapy to the tumors in the liver.

Certain factors affect prognosis (chance of recovery) and treatment options. 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).