Colon cancer is classified as Stage IV if the final evaluation following surgical removal of the cancer shows that the cancer has spread to distant locations in the body; this may include the liver, lungs, bones, distant lymph nodes or other sites. While it is commonly thought that patients diagnosed with Stage IV colon cancer have few treatment options, certain patients can still be cured of their cancer, and others can derive significant benefit from additional treatment.
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Patients with Stage IV colon cancer can be broadly divided into two groups:
- Those with widespread, metastatic cancer that cannot be treated with surgery (sometimes called unresectable cancer )
- Those with cancer that has metastasized to a single site
When the site of metastasis is a single organ (such as the liver), and the cancer is confined to a single defined area within the organ, patients may benefit from local treatment directed at that single metastasis.
The majority of patients diagnosed with Stage IV colon cancer have unresectable or widespread disease. Historically, treatment outcomes for these patients were poor. However, new combinations of chemotherapy drugs and the addition of targeted therapies such as Avastin® (bevacizumab) have improved outcomes.
The following is a general overview of the diagnosis and treatment of stage IV colon cancer. Each person with colon cancer is different, and the specific characteristics of your condition will determine how it is managed. The information on this Web site is intended to help educate you about treatment options and to facilitate a shared decision-making process with your treating physician.
The information on this website is intended to help educate patients about their treatment options and to facilitate a mutual or shared decision-making process with their treating cancer physician.
This section covers the initial, also called first-line, treatment of Stage IV colon cancer. For information about the treatment of cancer that has recurred or progressed after initial treatment, visit Recurrent Colon Cancer.
For over 30 years the chemotherapy drug fluorouracil (5-FU) was the standard treatment for metastatic Stage IV colon cancer that had spread to several sites in the body. 5-FU is typically administered with leucovorin, a drug that is similar in structure and function to the essential vitamin folic acid. Leucovorin (LV) enhances the anticancer effects of fluorouracil by helping the chemotherapy drug bind to and stay inside the cell for a greater period of time, producing longer lasting anticancer effects.
More recently, the addition of other drugs to 5-FU/LV has been found to provide additional benefit. Not all patients can tolerate these multi-drug regimens, however, and less intensive regimens are available.
Adding Targeted Therapy to Chemotherapy
Targeted therapies are anticancer drugs that interfere with specific pathways involved in cancer cell growth or survival. Some targeted therapies block growth signals from reaching cancer cells; others reduce the blood supply to cancer cells; and still others stimulate the immune system to recognize and attack the cancer cell. Depending on the specific “target”, targeted therapies may slow cancer cell growth or increase cancer cell death. Targeted therapies may be used in combination with other cancer treatments such as conventional chemotherapy. Recently approved targeted therapies represent the most novel advance in the treatment of metastatic colorectal cancer in the last few years.
Targeted therapies that have shown a benefit for selected patients with metastatic colorectal cancer include Avastin® (bevacizumab), Erbitux® (cetuximab), and Vectibix® (panitumumab). Avastin blocks a protein (VEGF) that plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Erbitux and Vectibix slow cancer growth by targeting a protein known as EGFR. Cancers with certain gene mutations are unlikely to respond to Erbitux or Vectibix, and tests are available to detect these mutations before treatment decisions are made.
Stage IV colon cancer commonly spreads to the liver or the lungs. Some patients who have cancer that has spread to a single area are candidates for surgery to remove the metastases.
Treatment of the liver: When it’s possible to completely surgically remove all liver metastases, surgery is the preferred treatment. Although surgery offers some patients the chance for a cure, a majority of patients with liver metastases are not candidates for surgery because of the size or location of their tumors or their general health. Some of these patients may become candidates for surgery if initial treatment with chemotherapy shrinks the tumors sufficiently. If the tumors continue to be impossible to remove surgically, other liver-directed therapies may be considered. These other therapies include radiofrequency ablation (use of heat to kill cancer cells), cryotherapy (use of cold to kill cancer cells), delivery of chemotherapy directly to the liver, and radiation therapy. Relatively little information is available from clinical trials about the risks and benefits of these other approaches, but they may benefit selected patients.1
Treatment of the Elderly
A large percentage of patients with advanced colorectal cancer are 65 years or older. Because elderly patients commonly have concurrent illnesses or other medical difficulties that are perceived to exacerbate the side effects of chemotherapy, elderly patients are often treated with reduced doses of chemotherapy. Clinical studies have shown, however, that elderly patients get the same benefit from chemotherapy treatment as younger patients.
While a dose reduction or delay may sometimes be necessary, it may also compromise the optimal treatment of some patients. All patients over 65 should be closely monitored for toxic side effects of chemotherapy, especially during their initial chemotherapy administration cycle.
1 Alsina J, Choti MA. Liver-directed therapies in colorectal cancer. Seminars in Oncology. 2011;38:651-567.