Cancer of the colon or rectum is the third most frequently diagnosed cancer in men and women in the U.S. Cancer of any portion of the large intestine is sometimes collectively referred to as colorectal cancer.

If you have been diagnosed with colon cancer, you probably have many questions and concerns about treatment. This patient summary, which is based on the NCCN Clinical Practice Guidelines in Oncology™, will help you understand the best available treatments for colon cancer. Talk to your doctor about these therapies so that together you can decide on a treatment plan that is right for you.

Background

The colon is part of the body’s digestive system. The digestive system removes and processes 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 first 6 feet of the large intestine are called the large bowel or colon. The last 6 inches are the rectum and the anal canal.

Most colon cancers are believed to start as a polyp, a small abnormal growth in the lining of the colon. However, most colon polyps will not turn out to be cancerous.

People who have a family history of colorectal cancer may have a slightly higher risk of developing the disease than do others. Smoking, a diet high in animal fat (and low in fiber), a history of having many noncancerous polyps in the colon, and other factors also increase a person’s risk for colorectal cancer. In addition, some of these factors may increase the risk that colorectal cancer will recur (come back) after treatment.

If other members of your family have had colon or rectal cancer, make sure your doctor knows.  Depending on how many and how close the family members are, your doctor may recommend genetic testing for you to determine whether you might have a genetic mutation that makes you more susceptible to colorectal cancer and genetic counseling for other members of your family.

Diagnosis

The diagnosis of metastatic (or stage IV) colorectal cancer may be made at the same time cancer of the colon or the rectum is first detected or some time after treatment of an earlier stage of colorectal cancer. Recurrent colorectal cancer is cancer that has returned following treatment. A recurrence of colon or rectal cancer can either be at or near the site of the original tumor (i.e., a local recurrence) or at a distant site (i.e., metastatic disease).

For those without a previous diagnosis of colorectal cancer, blood in the stool and/or the presence of a polyp or tumor in the colon or rectum (detected during a colonoscopy or sigmoidoscopy) may be the first sign of disease. Signs of metastatic disease that has spread to an organ such as the liver or lungs in those with either newly diagnosed or recurrent colorectal cancer may include abnormal results of blood tests (including the presence of the CEA [carcinoembryonic antigen] tumor marker and/or abnormal results of tests of liver function), or abnormal findings from imaging studies such as a computed tomography (CT) scan.  You may also have noticed some abdominal discomfort, loss of appetite, or aversion to meat—these are common symptoms of advanced colon or rectal cancer.

For those with no previous diagnosis of colorectal cancer, a biopsy from the tumor in the colon or rectum is needed to confirm or rule out colorectal cancer. In a biopsy, a sample of tissue or cells is removed so that it can be viewed under a microscope to check for abnormal cell growth.  If you have been newly diagnosed with cancer of the colon or rectum and your doctor suspects that the cancer has spread to another organ (for example, the liver), he or she may recommend another biopsy of the site where the cancer may have spread to confirm the diagnosis of metastatic colorectal cancer. For those with recurrent colorectal cancer with evidence of metastatic disease on imaging tests, a biopsy of a site of suspected metastatic disease should be done. For those diagnosed with metastatic colorectal cancer, the NCCN Guidelines recommend that a biopsy sample (either from the primary tumor or a site of metastatic disease) be tested to determine the status of the KRAS (pronounced “k-ras”) tumor marker on the cancer cells (see Targeted Therapy, below).

Colorectal cancer that has spread to other organs in the body is still colorectal cancer. If you have had a previous diagnosis of colorectal cancer, signs of cancer in your liver, lungs, or other sites are much more likely to be due to colorectal cancer than to be liver or lung cancer. This is important to know because treatments for colorectal cancer that has spread to liver or lung are very different than the treatments for cancer that starts in the liver or lungs.  It is also important that all sites of metastasis are identified because this can influence treatment recommendations.

Staging

Staging describes the extent or severity of a cancer diagnosis.  The stage gives information about the tumor and whether the cancer has spread to lymph nodes in the vicinity of the tumor, or to distant sites and other organs, such as the liver or lungs. See Cancer Staging Guide.

Stages of colon or rectal cancer go from 0 to IV, with the extent of disease increasing with increasing stage number. Stage is characterized by three factors:

• How deeply the tumor has penetrated the wall of the colon or rectum (i.e., which layer of the colon or rectal wall the tumor has reached)
• Whether cancer has spread to surrounding lymph nodes and, if so, the number of lymph nodes near the tumor that are affected
• Whether there is evidence of distant spread of disease. Patients with stage IV colorectal cancer have evidence of distant disease spread (metastasis). Stage IV colorectal cancer is defined solely by the presence of distant disease and does not depend on tumor penetration depth or disease spread to the lymph nodes near the tumor.

Treatment

If cancer of the colon or rectum returns after treatment of an earlier stage of the disease and has spread to other organs, NCCN recommendations for treatment do not consider whether the cancer originated in the colon or in the rectum; treatment recommendations are the same for either site of origin. However, if metastatic disease is found at the time of the original diagnosis of colon or rectal cancer, NCCN treatment recommendations may be different for those with metastatic colon cancer and those with metastatic rectal cancer.

Some cases of metastatic colorectal cancer (e.g., those in which the spread of cancer is limited to the liver and/or lungs) may be treatable with surgery, and may be curable (see section on Surgery, below). Although metastatic colorectal cancer that cannot be treated by surgery is not curable, there are many other effective treatments (see Chemotherapy and Targeted Therapy, below). The goal of treatment is to shrink or slow the growth of the cancer to help you feel as well as possible and live a longer life.
Your treatment is likely to involve a team of doctors, and may include a medical oncologist, a radiation oncologist, a radiologist, one or more surgeons, as well as other cancer specialists. It is very important that these doctors communicate with you and each other to develop the best treatment plan for you.

Treatment for those with stage IV/metastatic colorectal cancer is highly individualized; no single treatment plan is right for everyone. Doctors who treat advanced colorectal cancer refer to a continuum of care.  This means that there are a number of effective treatments and that they can be given sequentially, giving you a longer, higher quality of life.  To make the best decisions for you, talk to your doctors about the benefits, risks, and possible side effects of the treatment options below, and work with your doctors to develop an upfront, flexible treatment plan.

Your doctor should provide you with a written care plan explaining what treatments you will have, when they will occur and how often if you are receiving chemotherapy or radiation, and what type of side effects you may experience.  Some side effects can be anticipated, and you can be given pretreatment to minimize them.  You will be asked to sign an informed consent indicating that you have been told about your treatment and what to expect. It is very important that you ask your doctor or nurse every question that you have.  Cancer and its treatment are complicated and most patients have questions.

Surgery

Early evaluation by a surgeon with experience in surgery of the site(s) of the colorectal metastases is an important part of your care. A number of specific factors must be considered to determine whether surgery is an option for you and, if so, the type or types of surgical procedures that can be performed. These factors include:

• Any previous treatment(s) for colorectal cancer you may have received, that is, whether the cancer has been diagnosed for the first time or is recurrent.
• Whether the cancer originated in the colon or the rectum—this factor is only important if you have not already been treated for colon or rectal cancer.
• The site(s) of metastatic disease.
• Whether all metastatic disease can be surgically removed in such a way that the function of the affected organs can be maintained.
• Your overall health.

If you have been diagnosed with metastatic colorectal cancer that has recurred following treatment, it is likely that your earlier treatment involved surgery to remove the tumor in the colon or rectum. However, if you have been diagnosed with metastatic disease when colon or rectal cancer is first detected, your doctor may or may not recommend surgery to remove the tumor in the colon or rectum. NCCN Guidelines recommend that such surgery be performed only if there is the potential to also completely remove the metastatic disease. Surgery may be an option if the colon or rectal tumor is causing symptoms such as intestinal blockage or substantial bleeding. If surgery to remove both the colon or rectal tumor and the metastatic disease is planned, these procedures may be done during the same operation or at different times.

Different surgical approaches are used to remove tumors in the colon and rectum. (See Colon Cancer – Stages 0, I, II, and III and Rectal Cancer – Stages 0, I, II, and III ). In addition, your doctor may recommend that you receive either chemoradiation (see Chemoradiation, below) or chemotherapy with or without targeted therapy (see Chemotherapy and Targeted Therapy, below) before surgery to help shrink the tumors and to see how the disease responds to such therapy. Before surgery, either chemoradiation or chemotherapy (with or without targeted therapy) or both may be an option for those with metastatic rectal cancer, whereas only chemotherapy (with or without targeted therapy) is an option for those with metastatic colon cancer. In some cases, pre-treatment with chemoradiation or chemotherapy may make it possible for a patient to have surgery, although surgery may still not be an option for some patients even after these treatments.

Some patients report having loose stools following colon or rectal cancer surgery.   This is because as part of normal digestion, the colon reabsorbs water.  After surgery, the shorter colon has less room to reabsorb water, so your stools may be more watery than normal. 

The surgical approach used to remove metastatic disease depends on the site(s) of metastasis. Common sites of metastasis include the liver and the lung. Surgery to remove metastatic disease should involve complete removal of detectable disease while maintaining the function of the affected organs. Disease may also metastasize to other sites in the abdomen and pelvis as well as other locations in the body, although in most cases metastases in these locations are not treated by surgery.

Chemoradiation

Chemotherapy drugs are given to destroy or slow the growth of cancer cells that have spread beyond the tumor. Radiation therapy uses high-energy beams to kill cancer cells in a particular area of the body. In the treatment of rectal cancer, radiation therapy is focused in the pelvis.

The combination of chemotherapy with radiation therapy (ie, chemoradiation), when administered before surgery, is especially effective in the treatment of rectal cancer. Chemoradiation helps shrink the rectal tumor so that it can be more effectively removed during surgery. A tumor in the rectum—and the lymph nodes near the tumor to which cancer may have spread—is typically more difficult to completely remove than most tumors in the colon. Before surgery, a combination of chemotherapy and radiation therapy (chemoradiation) is an option if you have metastatic disease at the time of rectal cancer diagnosis and are a candidate for surgical removal of all evidence of metastatic disease.

If you do not receive pre-surgical chemoradiation, it may be given following surgery to help prevent return of the cancer to the rectum and its spread to more distant sites. A list of the chemoradiation therapy regimens that are preferred by the NCCN Panel can be viewed in the NCCN Rectal Cancer Guidelines. Chemoradiation is frequently given over a period of about five weeks.

Side effects of radiation therapy to the pelvis can include diarrhea, abdominal pressure or discomfort in the rectal area, a burning sensation during urination or more frequent urination, skin irritation, nausea and fatigue, and sexual side effects. Talk to your doctor or oncology nurse before radiation therapy to discuss ways to alleviate the discomfort. See Palliative Care Gets New Life. 

Chemotherapy

Chemotherapy to destroy or slow the growth of cancer cells is usually given as a combination of drugs.  See Guide to Chemotherapy.

Your doctor may recommend that you receive chemotherapy either before or after surgery. Chemotherapy is given before surgery to help shrink the tumor so that it can be more effectively removed during surgery. Chemotherapy is given after surgery mainly to destroy any cancer cells that may have spread beyond the site(s) of detectable metastatic disease. Presurgical chemotherapy is often administered over a period of a few months, while post-surgical chemotherapy is typically given over for about four to six months.

Another very important role for chemotherapy is to treat patients with metastatic colorectal cancer who cannot be treated surgically. Many new chemotherapy drugs and chemotherapy regimens have become available to treat metastatic colorectal cancer, and clinical studies have shown that  treatment with a variety of such drugs over time is beneficial.

The selection of a particular chemotherapy treatment depends, in part, on your general health.  Some chemotherapy treatments require that you be in good health to be treated.  If you are in poor health, especially if your poor health is related to your colorectal cancer, you may be able to have a milder form of chemotherapy;  if your health improves, you may have more intensive chemotherapy later.

Another important consideration is the likely side effects of each drug in the combination.  Your doctor will ask questions about your life, the activities that are important to you, and your specific concerns and take your answers into account in recommending treatment. 

A typical initial treatment strategy often involves a combination of chemotherapy drugs with a targeted therapy (see sections on Chemotherapy and Targeted Therapy, below). This regimen may be continued until it is no longer effective, or it is possible that one drug in the regimen may be stopped and you will receive a less intensive regimen for a period of time. This strategy is useful for limiting troublesome side effects of some drugs.  Later, this drug may be added back or your doctor may recommend moving to a different combination of drugs. This process can provide long-term cancer management for many of those with stage IV/metastatic colorectal cancer. The NCCN Guidelines include recommended chemotherapy regimen options and provide guidance on strategies for sequencing such therapies so that a continuity of care can be maintained.  Your doctor can find a listing of the chemotherapy regimens in the NCCN Colon Cancer and Rectal Cancer Guidelines (see NCCN Clinical Practice Guidelines in Oncology™).

If chemotherapy is an option for you, talk to your doctor about whether a more or less intensive regimen is the better choice. In addition, some chemotherapy regimens can have uncomfortable side effects such as one or more of the following:

• Intestinal disturbances (including nausea, vomiting, and/or diarrhea)
• Mouth sores
• Numbness and/or sensitivity to cold in the feet and/or hands
• A decreased production of certain types of blood cells
• Hair loss

Talk to your doctor or oncology nurse about how to manage these effects. Medications and other interventions can help with the side effects. It is important for you to let your doctor or nurse know about any side effects you experience as soon as they appear.

Targeted therapy

Some treatments are more specifically directed toward certain markers on tumor cells or certain processes occurring in tumor cells. For example, Avastin (bevacizumab) is a therapy that is targeted to a substance that helps blood vessels grow. This drug is thought to help decrease the production of new blood vessels supplying the tumor or tumors, thereby helping to “starve” the tumor of nutrients.

Other drugs like Erbitux (cetuximab) and Vectibix (panitumumab) target a protein on cells called the epidermal growth factor receptor (EGFR) and inhibit it, thereby interfering with some of the growth processes occurring in tumor cells. However, cetuximab and panitumumab are not beneficial for every patient with metastatic colorectal cancer. A very important factor to determine before deciding on whether an EGFR inhibitor is an option for you is the status of the KRAS tumor marker.

EGFR inhibitors have been found to be ineffective in people with a mutation in the KRAS gene (often simply referred to as KRAS and pronounced “k-ras”). The NCCN Guidelines recommend that the KRAS status (from either the primary tumor or a site of metastasis) be determined for all those with a diagnosis of metastatic colorectal cancer. If your tumor biopsy shows a mutation in the KRAS gene, an EGFR inhibitor is not recommended.

Targeted therapies may be given in combination with specific chemotherapy drugs or, in the case of the EGFR inhibitors, they may be given as single agents (see NCCN Guidelines for recommended regimens).

Targeted therapies can cause side effects. For example, bevacizumab can cause an elevation in blood pressure. An EGFR inhibitor can cause skin rash, although, in fact, the presence of the rash is believed to be an indicator that the drug is effective.  Talk with your doctor or oncology nurse about how to manage these effects. Medications can help with the side effects. It is important for you to share any possible side effects with your nurse or doctor as soon as they appear.

Supportive care

Your doctor may also recommend that you receive other therapies to relieve disease-related symptoms and to prevent other problems, such as certain drugs to control nausea related to chemotherapy or pain. Over time, the emphasis on supportive care likely will become a more and more important consideration in your treatment. See Palliative Care Gets New Life. 

Prognosis

In determining a prognosis—the likely course or outcome of a disease—a doctor may look at cancer survival statistics taken from studies of large groups of patients. However, such statistics:

• Are estimates only,
• Can vary widely with each cancer stage,
• Are sometimes based on older data that do not reflect recent advances in early detection and treatment,
• Cannot be used to precisely predict your survival.

Your individual prognosis will be affected by many factors, including:

• Your age,
• Your overall health,
• The type, stage, and grade of your cancer,
• The status of certain tumor markers, such as KRAS,
• Your response to the treatment(s) being used.

Ask your doctor which treatment(s), in his or her judgment, will give you the best life expectancy and quality of life. You may want to participate in a clinical trial, in which new and experimental therapies are tested in people with Stage IV/colorectal cancer.