Colorectal cancer

ALSO KNOWN AS: Colon cancer, rectal cancer, intestinal cancer

RELATED CONDITIONS: Familial adenomatous polyposis

DEFINITION: Colorectal cancer (CRC) is cancer of the colon, which is also called the large intestine, and the rectum. The cells of the colon and rectum become abnormal and lose the defining characteristics of normal intestinal cells and their ability to divide in a controlled way. These cells grow rapidly and form tumors. The large intestine includes the ascending colon, transverse colon, and sigmoid colon. The rectum and anus follow the sigmoid colon, where solid waste (feces or stool) exits the body.

Carcinoma, a cancer derived from epithelial cells, is the most common cell type found in CRC. Epithelial cells normally line the digestive system, glands, and make up the top layers of skin. Intestinal epithelial cells vary somewhat from those in other parts of the body.

Risk factors: Increasing age, a family history of colorectal cancer, familial polyposis, ulcerative colitis, and Crohn's disease increase risk. A high-fat, low-fiber diet, and inactivity can play a role, but the mechanism of this association is not known.

Etiology and the disease process: Some changes occur in the colon before cancer develops. A small area of precancerous cells will begin forming on the intestine's surface. These cells can mutate into cancerous cells and will continue to grow in both directions, outward from the surface and inward through deeper layers of tissue that form the multiple layers of the intestinal wall. As the abnormal growth invades these layers, it can encroach on blood vessels and lymph nodes, from which cancer cells can travel to the liver or other organs. Liver metastases are common with advanced disease.

The most common large intestine abnormality is noncancerous growths called polyps. Polyps grow into the intestine from its walls. Some polyps have a stalk. Polyps usually grow in the sigmoid colon and the rectum. Adenomatous polyps (derived from glandular tissue) are more likely to become (cancerous). Approximately 25 percent of people with colon cancer have polyps somewhere else in the large intestine.

Familial polyposis is a hereditary condition. There is a genetic predisposition to grow many, even one hundred or more precancerous adenomatous polyps in the large intestine. Cases of colorectal cancer due to this condition appear before the age of forty, unlike colorectal cancers due to other causes, which have a higher rate of incidence with advancing age. Polyps are removed unless there are so many of them that it is better to remove a section of the large intestine containing the polyps. Frequent examination of the large intestine is necessary to watch for new growth. The most extreme measure to prevent the growth of more polyps is the surgical removal of the rectum and anus. A surgical opening is made in the abdominal wall (ileostomy), where solid waste can be collected in a pouch.

Incidence: Colorectal cancer is a common and deadly cancer. Around one in twenty-three men and one in twenty-five women develop colorectal cancer at some point. It accounts for around 10 percent of all cancer cases worldwide. The incidence of colorectal cancer in people under age fifty increased by more than 50 percent between 1994 and 2021, though incidence in older adults steadily declined. The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program and the American Cancer Society (ACS) regularly publish statistics and information concerning cancer trends and incidence rates.

Symptoms: There are no symptoms of early colorectal cancer. Screening is the most important component in prevention and early detection. Symptoms such as weight loss, constipation, blood in the stool, and liver disease indicate a more advanced stage of disease.

Screening and diagnosis: There are several screening and diagnostic tests for colorectal cancer. The type and frequency of testing depend on the patient’s age and medical history. A fecal occult blood test/fecal immunochemical test (FOBT/FIT) is recommended in people over fifty. A physician decides which additional test—double-contrast barium X-ray, flexible sigmoidoscopy, or colonoscopy—should be given to each person. Many organizations recommend screenings start at age forty-five and repeat every five to ten years after for those without new symptoms.

• Fecal occult blood test (FOBT): Three fecal samples taken at different times are placed on special cards and sent to the laboratory for testing. The presence of blood in the sample indicates that further testing is required. A positive FOBT does not necessarily mean cancer. Blood can come from hemorrhoids, a noncancerous polyp, or inflammatory bowel diseases such as Crohn's disease or ulcerative colitis.
• Fecal immunochemical test (FIT): Also known as an immunochemical fecal occult blood test (iFOBT), to detect blood in the feces. The advantage to this test is that the patient is not required to restrict certain foods and medications before collecting the sample. Also, early evidence indicates that the FIT might be more specific in detecting blood than the FOBT.
• Double-contrast barium X-ray: An X-ray of the colon and rectum using barium for contrast. Growths, narrowing of the colon, and evidence of inflammation can be seen, as the barium outlines the large intestine. Biopsies and polyp removal are not possible with this procedure.
• Flexible sigmoidoscopy: The sigmoidoscope is a flexible tube with a light and a tiny camera at the tip. The instrument is introduced into the rectum. Polyps, other growths, and evidence of inflammation can be seen in the lower one-third of the intestine and rectum. Biopsies (tiny tissue samples) are taken of abnormal tissue.
• Colonoscopy: The colonoscope is a flexible tube with a light and tiny camera at the tip. The patient is given conscious sedation and frequently sleeps through the procedure. The tube is introduced through the rectum and is passed into all three sections of the large intestine. Biopsies of abnormalities can be taken. The colonoscopy is the only test that visualizes the entire colon and allows for biopsy of abnormalities.

If a biopsy is positive for cancer, further testing is required to see if the cancer has spread. The process is called staging.

• Stage 0: Very early cancer is present on the innermost layer of the intestine.
• Stage I: Cancer is in the inner layers of the colon.
• Stage II: Cancer has spread through the muscle wall of the colon.
• Stage III: Cancer has spread to the lymph nodes.
• Stage IV: Cancer has spread to other organs.

Treatment and therapy: Treatment options vary according to disease stage and the age and general health of the patient. The main treatment categories are surgery, chemotherapy, radiation therapy, and targeted therapy, which targets cancer cells by stimulating the immune system. More than one treatment may be used. Many patients choose to get a second opinion, allowing them to have increased confidence in the treatment option they have chosen with their physician or to explore other options. Colorectal cancer patients must ask questions necessary to feel confident that they understand the disease and treatment. Patients should take a trusted friend or family member to appointments and write down questions at home to ask their physician.

Surgery is the primary treatment. The type of surgery depends on the stage of the disease. Laparoscopic surgery, which involves a small incision in the abdomen, can remove some Stage 0 and Stage 1 tumors and cancerous polyps (polypectomy). Surgery in the early stages can be curative. Surgical procedures range from polypectomy, often performed during a colonoscopy, to resection (removal) of significant sections of the large intestine or rectum. When resection is performed, up to one-third of the intestine is removed. The ends of each section are then attached (anastomosis), where healthy tissue is present on each side. Cancer of the rectum and anus may require colectomy, a process in which the surgeon removes part or all of the colon, brings a normal section of the large intestine through an opening in the abdomen, and attaches a bag to collect solid waste.

External beam radiation therapy focuses high-energy beams directly into the tumor from outside the body, killing the cancer cells. Radiation usually follows surgery to remove a large mass or tumor. Radiation therapy is very precise and can be focused on small areas of tumor cells not seen during surgery. There are times when radiation is used before surgery to shrink a tumor and ease removal.

Radiation for colon cancer is performed with a linear accelerator. Precision calculations determine the most direct path to the tumor cells while damaging the fewest normal cells. Treatment lasts only a few minutes per day and might continue for several weeks.

Endocavitary radiation treatment for cancer of the rectum and anus is performed internally. A small, handheld device is introduced into the rectum, where the dose of radiation can more directly reach the cancer cells.

Side effects from radiation include skin irritation, nausea, bladder irritation, bowel incontinence, diarrhea, rectal irritation, and fatigue. Sexual dysfunction can occur in men and women.

Chemotherapy involves several strategies. It can be used after surgery when all evidence of cancer is gone, or it can work to prevent a return of the cancer, which is called adjuvant chemotherapy. Drugs used to treat colorectal cancer include fluorouracil (5-FU), capecitabine (Xeloda), oxaliplatin (Eloxatin), and irinotecan (Camptosar).

Systemic chemotherapy is the introduction into the body of toxic, cancer-fighting chemicals, which find cancer cells and kill them. Cancer cells divide more rapidly than normal cells. Chemotherapy drugs get inside the cancer cells more rapidly and kill them. A targeted variation is injecting chemotherapy drugs directly into an artery supplying blood to an organ (liver) that contains tumor cells.

Side effects of chemotherapy are due to the toxicity of the drugs, which kill cancerous and noncancerous cells. Common side effects are severe diarrhea, low blood counts, nausea, and vomiting. Medications are available to control the nausea and vomiting.

Targeted therapy exploits unique abnormalities of cancer cells other than rapid cell division. Proteins called monoclonal antibodies (mAbs or Moabs) selectively find the cancer cells and kill them. There are fewer side effects and less damage to normal cells. However, lung scarring, rashes, fatigue, infection, and allergic reactions are possible. Monoclonal antibody and target therapy drugs include bevacizumab (Avastin), cetuximab (Erbitux), and panitumumab (Vectibix).

Prognosis, prevention, and outcomes: People with a family history of colorectal cancer or polyps can take steps to lessen their chances of contracting it. High-fat, low-fiber diets are implicated in higher rates of CRC, but the mechanism is unknown. People who eat lean meat, smaller portions of meat, and more vegetables and grains have lower rates of CRC. Physical activity is also essential.

It is recommended that FOBT/FIT testing be performed yearly beginning at age forty-five and that colonoscopy, flexible sigmoidoscopy, or double-contrast barium X-ray be performed every five to ten years. Many people avoid these screening tests because of concerns about the colon-cleansing procedure before testing, unease about taking fecal samples, and embarrassment. However, these tests are critical because early detection is associated with excellent prognosis or cure. Stages 0, I, II, and III are potentially curable. Colorectal cancer that has not spread (metastasized) or invaded the intestinal wall has a greater chance of being cured. More than 90 percent of patients receiving treatment during the early stages will survive at least five years. Around 40 percent of colorectal cancer is found in the early stages, making the five-year survival rate 65 percent.

Stage IV cancer has spread to organs such as the liver, ovaries, lungs, or peritoneum. Surgery is performed not to cure the cancer but to prevent the colon from becoming blocked by the tumor. Liver metastases have been successfully removed through surgery. There have been some cures from this procedure, but this stage of disease is difficult to cure. Multiple therapies are used with Stage IV disease and include targeted therapies, chemotherapy, freezing tumors, and radiation.

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