The colon is the longest portion of the large intestine, also known as the large bowel. The large intestine is the last part of the digestive tract. It is a tube that is about 5 to 6 feet in length; the first 5 feet make up the colon, which then connects to about 6 inches of rectum, and finally ends with the anus. By the time food reaches the colon (about 3 to 8 hours after eating), the nutrients have been absorbed and the remainder is liquid waste product. The colon's function is to change this liquid waste into solid stool. The stool can spend anywhere from 10 hours to several days in the colon before being expelled through the anus. It has been suggested that the longer stool remains in the colon, the higher the risk for colon cancer, but this has not been proven.
Colon cancer is malignant tissue that grows in the wall of the colon. The majority of tumors begin when normal tissue in the colon wall forms an adenomatous polyp, or pre-cancerous growth projecting from the colon wall. As this polyp grows larger, the tumor is formed. This process can take many years, which allows time for early detection with screening tests.
Colon cancer is the third most common type of cancer, in both males and females, in the Western world. The incidence is highest in African Americans, who are also more likely to die of the disease. Certain factors put people at higher risk, but with about 108,000 new cases each year in the United States, we must all be aware of this deadly disease. The risk of colon cancer rises substantially after age 50, but every year there are numerous cases reported in younger people. Individuals with a personal or family history of colon cancer, polyps, or inherited colon cancer syndromes (i.e., FAP and HNPCC), as well as patients with ulcerative colitis or Crohn's disease, are all at higher risk and may require screening at an earlier age than the general population. A person with one first degree relative (parent, sibling or child) with colon cancer is 2 to 3 times as likely to develop the cancer as someone who does not have an affected relative.
However, this does not mean that people without a family history are not at risk. In fact, about 80% of new colon cancer cases are diagnosed in people who would not be identified as "high risk". Studies of colon cancer cases found that lifestyle factors may put a person at higher risk. These factors include: a diet high in fat and red meat but low in fruits and vegetables, high caloric intake, low levels of physical activity, and obesity. In addition, smoking and excessive alcohol intake may play a role in colon cancer development. Despite avoiding all of these factors, some people will still develop colon cancer. With screening and early detection, these patients can be effectively treated in a majority of the cases.
Given the things that put a person at higher risk, a low-fat diet high in fruits and vegetables and low in red meat, together with regular exercise and maintaining a healthy body weight, may aide in prevention. The term chemoprevention can be defined as 'the use of a chemical compound to prevent, inhibit, or reverse the formation of the cancer'. There are ongoing studies looking at vitamins A, E, D, and C, folic acid, calcium, selenium, aspirin, cox-2 inhibitors, statin medications (traditionally used to lower cholesterol) and hormone replacement therapy as potential chemopreventive agents that may prevent or reverse the formation of polyps and colon cancer. Thus far, these studies have been inconclusive, so no specific recommendations can be made for the general population. Some of these agents continue to be evaluated in clinical trials.
Some tumors and polyps may bleed intermittently, and this blood can be detected in stool samples by a test called fecal occult blood testing (FOBT). By itself, FOBT only finds about 24% of cancers. It is recommended by the American Cancer Society that FOBT be done annually, in conjunction with a flexible sigmoidoscopy every 5 years after age 50. This combination of tests detects about 76% of colon tumors. The sigmoidoscope is a slender, flexible tube that has the ability to view about 1/3 of the colon. If a polyp or tumor is detected with this test, the patient must be referred for a full colonoscopy to have the polyp removed and tested for cancer.
The colonoscope is similar to the sigmoidoscope, but is longer and thus can view the entire colon. If a polyp is found, the physician can remove it and send it to a pathology lab to determine if it is adenomatous (cancerous). As a screening method, the American Cancer Society ( ACS ) recommends that a colonoscopy be done every 10 years after age 50; alternatives include CT colonography (virtual colonoscopy) every 5 years or flexible sigmoidoscopy every 5 years. Patients with a family or personal history should have more frequent screenings, beginning at an earlier age than their relative was when he or she was diagnosed. Patients with a history of inflammatory bowel disease, including ulcerative colitis, are also at increased risk and should have more frequent screening than the general public. No screening modality is perfect. For colonoscopy, the rate of missed lesions is 2-12%.
If a polyp is found on CT colonography, the person would need to have a colonoscopy to biopsy the polyp. The US Preventive Task Force does not recommend CT colonography for general screening. This test is not as good at finding flat polyps, and large flat polyps have a higher risk of developing into colon cancer. Up to 16% of people having their first CT colonography are found to have abnormalities outside the colon that require further testing. In identifying and investigating these abnormalities, there is potential for both benefit and harm. Potential harms arise from additional diagnostic testing and procedures for these lesions found incidentally, which may have no clinical significance. This additional testing also has the potential to burden the patient with additional time off work and costs. The risks for perforation associated with screening CT colonography in research settings are estimated to be 0 to 6 per 10,000 studies. However, these estimates may be higher than what can be expected in screened populations because the studies included testing in symptomatic people.
Radiation exposure resulting from CT colonography is reported to be 10 mSv per examination. The harms of radiation at this dose are not certain, but one model predicts that 1 additional individual per 1000 would develop cancer in his or her lifetime at this level of exposure. There is growing research about increased cancer risk due to cumulative radiation exposure from the use of diagnostic and screening tests that involve radiation exposure. On the other hand, improvements in CT colonography technology and practice are lowering this radiation dose.
Patients should talk with their physicians about which screening method is best for them, and how often it should be performed. You can learn more about screening by reading Basic Information about Colorectal Cancer and Colorectal Cancer Screening. You can also learn about virtual colonoscopy and DNA stool testing.
Evidence that colonoscopy actually decreases colon cancer deaths is derived from cohort and case control studies (indirect evidence). For example, a study from Ontario, Canada comparing rates of colonoscopy found that for every 1% increase in colonoscopy screening there was a 3% decrease in death from colon cancer. Randomized trials are ongoing.
Despite the effectiveness of screening tests for colon cancer, one study found that only 44% of adults who are age 50 and older had undergone testing. Recent media focus, including Katie Couric's efforts and ACS commercials, has helped to raise public awareness of this cancer, but more education is needed.
Unfortunately, the early stages of colon cancer may not have any symptoms. This is why it is important to have screening tests done even though you may feel well. As the polyp grows into a tumor, it may bleed or obstruct the colon, causing symptoms. These symptoms include:
As you can see, these symptoms can also be caused by conditions other than cancer. If you experience these symptoms, you should be checked by a doctor.
After a cancer has been found, the stage must be determined to decide on appropriate treatment. The stage tells how far the tumor has invaded into the colon wall, and if it has spread to other parts of the body.
Because the staging system is relatively detailed, a more simplified way of understanding the stage groupings is:
After the tumor and lymph nodes are removed by a surgeon, they are examined by a pathologist, who determines how much of the colon wall and lymph nodes have been invaded by tumor. See Understanding Your Pathology Report for more information. Patients with invasive cancer (stages II, III, and IV) require a staging workup, including full colonoscopy, carcinoembryonic antigen (CEA) level (a marker for colon cancer found in the blood), chest x-ray, and CT scan of the abdomen and pelvis, to determine if the cancer has spread.
Surgery is the most common treatment for colon cancer. If the cancer is limited to a polyp, the patient can undergo a polypectomy (removal of the polyp), or a local excision, where a small amount of surrounding tissue is also removed. If the tumor invades the bowel wall or surrounding tissues, the patient will require a partial resection (removal of the cancer and a portion of the bowel) and removal of local lymph nodes to determine if the cancer has spread into them. After the tumor is removed, the two ends of the remaining colon are reconnected, allowing normal bowel function. In some situations, it may not be possible to reconnect the colon, and a colostomy (an opening in the abdominal wall to allow passage of stool) is needed, which may be temporary or permanent.
Despite the fact that a majority of patients have the entire tumor removed by surgery, as many as 50 to 60% will develop a recurrence without further treatment. Chemotherapy is given to reduce this chance of recurrence, particularly when initiated within 4 week of surgery. There is some controversy over whether or not patients with stage II disease should receive chemotherapy. Studies have not consistently shown a benefit in treating these patients or have shown only a very small benefit. Many patients with stage II disease are followed closely, but receive no chemotherapy. Generally, patients with stage II disease who present with a bowel perforation or obstruction, or who have large or poorly differentiated tumors (determined by a pathologist looking at the tumor under a microscope), are considered at higher risk for recurrence and are treated with 6 months of fluorouracil (5-FU), leucovorin (LV), with or without oxaliplatin chemotherapy. Work is being done to further clarify who among the stage II group is high risk, which will be help doctors make treatment decisions. Several groups are using molecular and genetic markers to study risk-assessment in stage II patients.
Patients who present with stage III colon cancer are treated with a regimen of chemotherapy, including some combination of fluorouracil (5-FU), leucovorin, and oxaliplatin for 6 months, resulting in improved survival rates when compared with surgery alone. The addition of other agents, including irinotecan and bevacizumab, in combination with 5-FU/LV has not been shown to benefit stage III patients. After completion of this therapy, they are monitored for recurrence of the disease. Capecitabine (Xeloda), an oral form of fluorouracil, is being used more frequently as a replacement for IV 5-FU and a randomized trial of Xeloda plus oxaliplatin vs IV 5-FU plus oxaliplatin awaits final results.
Forty to fifty percent of patients have metastatic disease (cancer that has spread to other organs, also called stage IV) at the time of diagnosis, or have a recurrence of the disease after therapy. Unfortunately, with the exception of selected patients who have limited liver metastases, stage IV disease is not considered cureable. Nevertheless, patients can have improved quality of life and longer survival with chemotherapy treatment. The standard therapy for patients with advanced disease is some combination of fluorouracil, leucovorin, irinotecan (CPT-11 or Camptosar), oxaliplatin (Eloxitin) , bevacizumab (Avastin), cetuximab (Erbitux), and capecitabine. Regimens adding either irinotecan or oxaliplatin to fluorouracil and leucovorin were found to be more effective than using the fluorouracil and leucovorin alone. With this therapy, an average of 39% of patients have a response, but the average survival is still only 20 months.
Targeted therapies are drug treatments that target a specific abnormality found in the cancer cells. The following are targeted therapies that are commonly used in the treatment of colon cancer.
Bevacizumab (Avastin) is a type of treatment called anti-angiogenic therapy. Tumors need nutrients to survive and are able to get these nutrients by growing new blood vessels. This medication works by attacking the new blood vessels the tumor has formed -- in other words, by cutting off its food source. Bevacizumab is used in combination with chemotherapy for patients with metastatic disease.
Cetuximab (Erbitux) and panitumumab (Vectibix) are types of monoclonal antibodies that target cancer cells specifically, sparing the normal cells and therefore causing fewer side effects. Cetuximab causes the patient's immune system to recognize the cancer cells as foreign and attack them and is given either alone or in conjunction with chemotherapy agents. It is generally reserved for patients who do not have a mutation in a particular gene called k-ras.
Epidermal growth factor receptor (EGFR) is abnormally over expressed in many cancers (including those of the colon and rectum), so inhibition of EGFR can result in a decrease in tumor cell growth and decreased production of other factors responsible for metastasis (tumor spread). Panitumumab exerts its cancer fighting properties by competitively inhibiting the binding of epidermal growth factor to EGFR, which prevents epidermal growth factor from working and hence not allowing cancer growth to occur. Patients and their physicians must weigh the benefits of therapy versus the side effects of the treatment. Patients who are younger and/or in better physical shape are more likely to tolerate therapy, but elderly patients should not be excluded from chemotherapy based on age alone.
Colon cancer is not typically treated with radiation therapy. If the cancer has invaded another organ, or attached itself to the abdominal wall, radiation therapy may be a treatment option. One reason for the limited role of radiation is that it is a local treatment typically aimed at a "target." Once the colon cancer has been surgically resected, the "target" or high-risk area for disease recurrence is not very easy to define. Furthermore, if the cancer has spread to other organs, chemotherapy (rather than radiation therapy) is able to reach distant areas spread of tumor cells.
Interventional radiologists are specialists who use radiology techniques, such as CT scan, to access areas of the body and treat diseases without traditional surgery. These techniques are sometimes called "minimally invasive". In some cases, these physicians are able to help patients with colon cancer that has metastasized to the liver or lung. The techniques currently being used by these specialists include: CT directed biopsies, chemoembolization, radiofrequency ablation and radioembolization. By entering a patient's blood vessels, the physician can thread a catheter all the way to the liver and give treatment directly to the tumor.
Radiofrequency ablation (RFA) is a local treatment that kills the tumor cells with heat, while sparing healthy liver tissue. When the tumor is too large or in a location not amenable to RFA, embolization may be used to cut off the blood supply to the tumor, deliver radiation to a tumor (radioembolization), or combine this technique with chemotherapy to deliver the cancer drug directly to the tumor (chemoembolization). These therapies are not considered curative, but can provide improved quality of life and extend survival.
Some patients may benefit from having an infusion pump inserted to infuse chemotherapy directly into the liver. IR physicians can also perform palliative procedures, such as inserting a stent to relieve an obstruction, treating certain types of pain, inserting central catheters or treating blood clots.
Once a patient has completed chemotherapy, they must be followed closely for recurrence. The guidelines for follow-up surveillance, written by the National Comprehensive Cancer Network are: physical exam (including digital rectal exam) every 3 months for 2 years, then every 6 months for 3 years; CEA level (if elevated preoperatively) checked every 3 months for 2 years, then every 6 months for 3 years; and colonoscopy in 1 year, with a repeat in 1 year if abnormal, or every 2-3 years if no polyps are found. There is not enough evidence to support or refute the use of chest x-ray or CT scan for surveillance at this time, so this varies from physician to physician and is more likely used in higher risk cases.
Clinical trials have played and continue to play an important role in the treatment of colon cancer. In the past 20 years, considerable improvements have been made in colon cancer therapy, with overall survival rates increasing from 45 to 75 percent. The treatments we have today were refined through clinical trials, and many new avenues continue to be explored. Talk with your physician about current clinical trials for colon cancer in your area or visit our clinical trials matching service.
This article is meant to give you a better understanding of colon cancer. Use this knowledge when meeting with your physician, making treatment decisions, and continuing your search for information. You can learn more about colon cancer on OncoLink through the related links on the left.
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