Colon Cancer Treatment
A diagnosis of cancer will lead to staging and other tests to help determine the outlook and the appropriate treatments. Treatment for colorectal cancer includes surgery, chemotherapy, and radiation. These treatment methods may be combined.
- Surgery is used for early-stage colorectal cancer. Usually, the tumor is removed along with part of the colon and nearby lymph nodes.
- Chemotherapy may be given after surgery to kill any remaining cancer cells. It may also be given along with radiation before surgery to reduce tumor size.
- Radiation therapy is not usually used in early-stage colon cancer, but is commonly used to treat early-stage rectal cancer. It is often combined with chemotherapy.
- Clinical trials are available for individual stages of colorectal cancer.
There are several methods for staging colorectal cancer. The older system, known as Dukes', categorizes four basic stages: A, B, C, and D. The newer TMN system evaluates the tumor (T), lymph node (N), and how far the cancer has spread or metastasized (M). The results of TMN are combined to determine the stage of the cancer.
Colorectal cancer stages and treatment options are: Stage 0 (Carcinoma in situ).
- In stage 0, cancer cells are fully contained in the innermost lining (mucosa) of the colon or rectum, and have not yet invaded the wall of the colon
- Treatment for stage 0 cancer usually involves surgical removal of the polyp (polypectomy) during colonoscopy.
- In stage I, the cancer has spread through the mucosa of the colon wall into middle layers of tissue.
- Treatment for stage I involves resection of the tumor. The tumor may be removed along with part of the colon (colectomy).
- In stage IIA, the cancer has spread beyond the middle layers to the outer tissues of the colon or rectum. In stage IIB, the cancer has penetrated through the colon or rectum wall into nearby tissue or organs.
- Treatment for stage II cancer involves surgical resection. Chemotherapy after surgery (adjuvant chemotherapy) plus radiation is considered standard treatment for stage II rectal cancer, but is under debate for stage II colon cancer.
- In stage III, lymph nodes are involved but not distant sites. Stage IIIA and IIIB cancer has spread to as many as three lymph nodes. Stage IIIC cancer involves four or more lymph nodes.
- Treatment for stage III colon cancer involves surgery and adjuvant chemotherapy with the FOLFOX regimen (5-FU, leucovorin, oxaliplatin). For patients with stage III rectal cancer, treatment includes chemotherapy and radiation, either before or following surgery.
- Stage IV is metastasized cancer. The cancer has spread to nearby lymph nodes and to other organs of the body such as the liver or lungs.
- Treatment for stage IV cancer may sometimes include surgery. When cancer has spread, surgery to remove or bypass obstructions in the intestine may be performed. In these circumstances, surgery is considered palliative in that it may improve symptoms but will not lead to cure. In some cases, surgery may also be performed to remove tumors in areas that the cancer has spread, such as the liver, ovaries, or lung.
- Chemotherapy is standard treatment for metastasized cancer. In advanced colorectal cancer, chemotherapy is either given directly into the arteries of the liver when it is involved or intravenously (through a vein) with 5-FU and leucovorin. The targeted therapy biologic drug bevacizumab may also be added. Other alternative chemotherapy choices are capecitabine, or irinotecan combined with cetuximab. Radiation therapy may be used in place of chemotherapy or in combination with it. Studies indicate that chemotherapy offers only a modest improvement in survival, but may help reduce symptoms.
Colorectal cancer is among the most curable of cancers when it is caught in its early stages. The term "5-year survival" means that patients have lived at least 5 years since diagnosis. The 5-year survival rate for colon cancer diagnosed and treated at stage I is 74%. The rates fall to 37 - 67% for stage II, 28 - 73% for stage III, and 6% for stage IV. However, there are other factors, including the appearance of cancer cells under the microscope, which can contribute to a patient's prognosis.
Doctors recommend follow-up testing to detect recurring cancer after the completion of treatment. General guidelines include:
Physical Examination. Most colorectal cancer recurrences happen within 3 years after surgery. Patients should see their doctors for a physical examination every 3 - 6 months for the first 2 years following surgery, every 6 months through the fifth year, and at the doctor's and patient's discretion during subsequent years.
Colonoscopy. Patients should have a colonoscopy 1 year after surgery. If the results are normal, patients should then receive a colonoscopy 3 years later and then every 5 years. Patients with abnormal results or who have hereditary types of cancer may need more frequent screenings.
A flexible sigmoidoscopy is recommended every 6 months for 5 years for patients with Stage II or III rectal cancer who did not receive radiation therapy.
Carcinoembryonic Antigen Levels. Carcinoembryonic antigen (CEA) levels should be measured every 3 - 6 months after surgery for 2 years in patients, and then every 6 months up to 5 years for patients with Stage II or III cancer. High CEA levels in the blood may indicate that the cancer has recurred or has spread to other parts of the body.
Imaging Tests. Patients at high risk for cancer recurrence should receive an annual computerized tomography (CT) scan of the chest, abdomen, and pelvis for the first 3 years after treatment. The CT scan can help determine if cancer has spread to the lungs or liver. Patients who have had rectal cancer, and did not have radiation therapy, should receive a pelvic CT scan. The scan is not recommended for most lower-risk patients with Stage I or II colorectal cancer. PET scans are not routinely recommended.
Other Tests. The American Society of Clinical Oncology does not recommend other follow-up blood tests such as complete blood count, liver function tests, and fecal occult blood tests. There appears to be no additional benefit for these tests.
In the earliest stages of colorectal cancer (stage 0 and some stage I cases) polyps can be removed during a colonoscopy in a procedure called polypectomy. Early-stage superficial cancers that are not deep can also be removed through excision, where the cancer is cut out by inserting a tube into the rectum. Unlike colectomy, these procedures do not involve cutting through the abdominal wall.
Surgical removal of the tumor ("resection") along with any affected surrounding tissue is the standard initial treatment for potentially curable colorectal cancers (cancers that have not spread beyond the colon or lymph nodes). Drug and radiation therapy are often used for advanced cancers and are continuously being tested with surgery in different combinations and sequences.
Although choosing a qualified surgeon is critical, choosing a hospital experienced in procedures is also important. The more often colon cancer surgery is performed at a given hospital, the lower the mortality rate at that hospital is likely to be.
Unless cancer is very advanced, most tumors are removed by an operation known as colectomy:
- Colectomy involves removing the cancerous part of the colon and nearby lymph nodes.
- The surgeon then reconnects the intestine in a procedure called anastomosis.
- If the surgeon cannot reconnect the intestine, usually because of infection or obstruction, the surgeon will perform a colostomy. Colostomy is a surgical procedure that brings one end of the large intestine out through the abdominal wall. Stools moving through the intestine drain into a bag (ostomy pouch) attached to the abdomen. The need for colostomies is higher after surgery for rectal cancer. In most cases of colon cancer, colostomies are not needed. [See "Colostomy" below.]
- Stents, expandable metal tube-like devices, may be used as preparation before surgery to remove blockage and to keep the intestine open.
The Surgical Approach. The standard technique for a colectomy is open, invasive surgery. Laparoscopy, sometimes called “keyhole surgery,” is a newer less invasive method.
- Open surgery uses a wide incision to open the patient's abdomen. The surgeon then performs the procedures with standard surgical instruments. This is the usual method for performing colectomy.
- Laparoscopy uses a few small incisions through which the surgeon passes a fiber optic tube (laparoscope) containing a small camera or tiny instruments. It is generally used for early colon cancer (for tumors less than 2 centimeters or for well-defined tumors less than 3 centimeters).
A colostomy is performed in order to bypass or remove the lower colon and rectum. The procedure generally involves creating a passage, called a stoma, through the abdominal wall that is connected to the colon. The feces pass through this passage and are eliminated. Patients must learn how to care for the stoma and keep the area sanitary.
A colostomy usually will have one opening (single-barreled), or there may be two loops opening through the skin (double-barreled).
Usually the colostomy is temporary and can be reversed by a second operation after about 3 - 6 months. If the rectum and sphincter muscles in the rectum need to be removed, the colostomy is permanent. Permanent colostomies are more common when the cancerous regions are within 2 - 3 centimeters of the anus. Fortunately, surgical advances and knowledge of the extent of safe margins are reducing the need for permanent colostomies.
Managing Permanent Colostomies. In cases where the colostomy is permanent, the patient must wear a colostomy pouch, which sticks to the skin using a special glue.
For best results, the pouch should be emptied when about one-third full. It should be replaced 1 - 2 times a week, depending on signs of leakage (itching or burning of the skin near the stoma). The pouches are odor proof.
Surgical treatments for cancer in the rectum are complex since they involve muscles and tissue that are critical for urinary and sexual function.
Local Excision or Polypectomy for Early Stages. In order to preserve the function of the anal sphincter and prevent the need for colostomy, Stage I and Stage II tumors may be removed by local excision, sometimes followed by chemotherapy and radiation. In this procedure, the tumor is cut out without removal of a major section of rectum. In some cases cancer recurs, but a second operation may be possible.
Radical Resection. In about a third of cases of rectal cancer, the cancer occurs in the lower part of the rectum, spreading beyond the rectal wall. These patients need a radical resection, in which surrounding structures, including the sphincter muscles that control bowel movements, must often be removed.
Total Mesorectal Excision. Total mesorectal excision (TME) involves dissection and removal of the entire cancerous area of the rectum along with surrounding fatty regions where the lymph nodes are located (the mesorectum). When successful, TME preserves the sphincter muscle, reducing the need for a permanent colostomy.
Side effects of colon surgery may include:
- Sexual dysfunction. In general, colostomy does not usually affect sexual function. However, wide rectal surgery can cause short- or long-term sexual dysfunction. PDE5 inhibitor drugs such as sildenafil (Viagra), vardenafil (Levitra), or tadalafil (Cialis) may help men who experience this after surgery.
- Irregular bowel movements.
- Gas and flatulence. Pouching filters are available to reduce gas. Certain foods produce more gas than others -- usually within 6 - 8 hours after ingestion -- for colostomy patients. They include beans, oat bran, most fruit, and certain vegetables (cabbage, cauliflower, Brussels sprouts, broccoli, and asparagus). To prevent swallowing air, patients should avoid sipping through straws, chewing gum, and chewing with their mouths open.
- Bladder complications.
- Sense of urinary urgency.
- Fecal incontinence. Patients with rectal surgery have a higher risk for bowel dysfunction than those who had a colostomy.
- Complications in or around the stoma. These can occur early after surgery to many years after the procedure. They include skin infection or breakdown, hernias, narrowing of the stoma, bleeding, and collapse.
There are no dietary restrictions, although many patients avoid foods that can produce gas. Everyone should drink plenty of fluids and get sufficient fiber.
The potential side effects of sexual and bowel dysfunction following colorectal surgery can be very difficult, although many patients do very well and live normal productive lives. Patients who are depressed should discuss with a doctor all aspects of treatment that affect the quality of life, and consider seeking support groups.
Seven drugs are currently approved for colorectal cancer chemotherapy:
- 5-fluorouracil (5-FU, Adrucil), which is often given in combination with leucovorin (Wellcovorin). Leucovorin helps boost the effectiveness of 5-FU.
- Capecitabine (Xeloda)
- Oxaliplatin (Eloxatin)
- Irinotecan (Camptosar)
- Bevacizumab (Avastin)
- Cetuximab (Erbitux)
- Panitumumab (Vectibix)
Capecitabine is a pill form of 5-FU. The other drugs are administered intravenously. Many of these drugs are given in combination with each other. Common chemotherapy combination regimens include:
- 5-FU / LV (5-FU and leucovorin)
- FOLFOX (5-FU with leucovorin and oxaliplatin)
- FOLFORI (5-FU with leucovorin and irinotecan)
- IFL (Irinotecan, 5-FU, leucovorin)
- XELOX (Capecitabine and oxaliplatin)
Side effects occur with all chemotherapeutic drugs. They are more severe with higher doses and increase over the course of treatment. Because cancer cells grow and divide rapidly, chemotherapy drugs work by killing fast-growing cells. This means that healthy cells that multiply quickly can also be affected. The fast-growing normal cells most likely to be affected are blood cells forming in the bone marrow, and cells in the digestive tract, reproductive system, and hair follicles.
Nausea and vomiting are very common side effects, but drugs such as ondansetron (Zofran) can help provide relief. In general, side effects are nearly always temporary, and medications can help manage them.
5-Fluorouracil (5-FU) with Leucovorin. Adjuvant (following surgery) chemotherapy using 5-fluorouracil, either alone or with leucovorin (5-FU/LV), is the standard treatment for patients with high-risk colon cancer (Stage III or select patients with Stage II tumors). Patients are given a series of cycles that usually continue for at least 6 months. Leucovorin, is related to folinic acid, a form of the B vitamin folic acid, and helps increase 5-FU’s effectiveness. If leucovorin is not available, a related drug, levoleucovorin (Fusilev), may be given as an alternative. Levoleucovorin in combination with 5-FU is approved for palliative (symptom) treatment of advanced metastatic cancer.
There are many different ways of giving 5-FU, including intravenously over several hours once a week, intravenously daily for 5 consecutive days every month, or as continuous infusion with a portable pump. The most common side effects include nausea and vomiting, diarrhea, loss of appetite, hair loss, swelling of hands and feet, rashes, and mouth sores.
Irinotecan. Irinotecan (Camptosar) blocks an enzyme essential for cell division. Irinotecan can be given alone or in combination with 5-FU and leucovorin. This combination therapy (irinotecan plus 5-FU/LV) is also referred to as the "Salz regimen," or IFL. Diarrhea is a common side effect of irinotecan.
Capecitabine. Capecitabine (Xeloda), a pill form of 5-FU, is used as a treatment for stage III and stage IV (metastatic) colorectal cancer. It is the only pill approved for colorectal cancer. Oxaliplatin. Oxaliplatin (Eloxatin) is related to cisplatin, a widely used platinum-based chemotherapy drug. Oxaliplatin is used in combination with 5-FU and leucovorin. This triple combination therapy is called the FOLFOX regimen. Capecitabine may also be used in combination with bevacizumab as a treatment option for initial therapy of advanced or metastatic cancer.
Oxaliplatin. Oxaliplatin (Eloxatin) is related to cisplatin, a widely used platinum-based chemotherapy drug. Oxaliplatin is used in combination with 5-FU and leucovorin in the FOLFOX regimen. Oxaliplatin can cause pain and tingling sensations in the hands and feet (neuropathy) that is worsened by exposure to cold.
Traditional chemotherapy drugs can be effective, but because they do not distinguish between healthy and cancerous cells their generalized toxicity can cause severe side effects. “Targeted therapies” work on a molecular level by blocking specific mechanisms associated with cancer cell growth and division.
Many targeted therapies are classified as biologic drugs. Bevacizumab (Avastin), cetixumab (Erbitux), and panitumumab (Vectibix) are currently the three biologic drugs approved for colorectal cancer treatment. They are used to treat metastatic colorectal cancer (advanced cancer that has spread from the colon or rectum to other parts of the body).
Bevacizumab. Bevacizumab (Avastin) is approved as a first-line treatment for patients with metastatic colorectal cancer. It is used in combination with IFL (irinotecan, 5-FU, leucovorin). Bevacizumab is a biologic anti-angiogenic drug. It is a genetically engineered monoclonal antibody that targets and inhibits vascular endothelial growth factor (VEGF), a protein that regulates angiogenesis (the development of new blood vessels that feed a tumor's blood supply).
Bevacizumab administered intravenously along with IFL extends survival by about 5 months longer than IFL alone. Common side effects of bevacizumab include nosebleeds, fatigue, diarrhea, and high blood pressure. Less common side effects include stroke, heart attacks, angina, and formation of holes in the colon and stomach (gastrointestinal perforation).
Cetuximab. Cetuximab (Erbitux) is a monoclonal antibody drug that targets epidermal growth factor receptor (EGFR), a protein required by cancer cells in order to proliferate. It can be used either in combination with irinotecan or alone for patients who have not responded to irinotecan. Studies of the cetuximab-irinotecan combination suggest it can help in tumor shrinkage. It has a modest effect on survival, prolonging patients' lives by about an additional month or two. Recent guidelines recommend that cetuximab, and panitumumab (see below), should be given only to patients with tumors that express the wild-type KRAS gene. Patients with metastatic cancer should have tumors tested for KRAS gene status.
Panitumumab. Panitumumab (Vectibix) is approved for treatment of colorectal cancer that has metastasized following standard chemotherapy. Like cetuximab, panitumumab is a monoclonal antibody drug that targets EGFR. In clinical trials, panitumumab helped delay disease progression and prolong survival by about 3 months. About 8% of patients experienced tumor shrinkage. Common side effects of this drug include skin rash, fatigue, abdominal pain, nausea, and diarrhea or constipation. Serious side effects include pulmonary fibrosis, severe skin rash, and skin reactions at the infusion site.
Tumor Growth Factor Inhibitors. Tumor growth factors, such as epidermal growth factor, stimulate cell growth. Cetixumab (Erbitux) and panitumumab (Vectibix) are the two currently approved colorectal cancer drugs that target the epidermal growth factor receptor (EGFR). Nimotuzumab (TheraCIM) is currently being studied in combination with irinotecan.
Tyrosine Kinase Inhibitors. Tyrosine kinase is an enzyme associated with EGFR that is involved with the signaling mechanisms that prompt cell growth. The EGFR/tyrosine kinase inhibitor erlotinib (Tarceva), which is approved for the treatment of pancreatic and lung cancers, is being investigated as an adjuvant treatment for metastatic colorectal cancer.
Radiation therapy uses x-rays to kill cancer cells that might remain after an operation or to shrink large tumors before an operation so that they can be removed surgically. The object of radiation therapy is to damage the tumor as much as possible without harming surrounding tissues. Radiation may be administered in one of the following two ways:
- Externally from a source outside the body, such as a linear accelerator (external beam radiation)
- Internally through small radioactive pellets implanted directly into the tumor (brachytherapy)
The main use for radiation therapy in people with colon cancer is when the cancer has attached to an internal organ or the lining of the abdomen. When this occurs, the surgeon cannot be certain that all the cancer has been removed, and radiation therapy may be used to kill any cancer cells remaining after surgery. Radiation therapy is seldom used to treat metastatic colon cancer because of side effects, which limit the dose that can be used.
For rectal cancer, radiation therapy is usually given to help prevent the cancer from coming back in the pelvis where the tumor started. It may be given either before or after surgery, but recently doctors have begun to favor preoperative treatment, along with chemotherapy. If a rectal cancer's size or position make surgery difficult, radiation may be used before surgery to shrink the tumor. Radiation therapy can also be given to help control rectal cancers in people who are not healthy enough for surgery.
Radiation also may be used to ease (palliate) symptoms in people with advanced cancer causing intestinal blockage, bleeding, or pain.
Radiation treatment is often combined with chemotherapy. Chemotherapy helps make the radiation treatment more effective. Radiation therapy is more often used for rectal cancer but may also be used in some cases for colon cancer.
Radiation for Colon Cancer. Radiation for colon cancer is given after surgery (postoperative or adjuvant radiation) to destroy any remaining cancer cells. It is generally not used to treat metastatic colon cancer.
Radiation for Rectal Cancer. Adjuvant radiation is a common practice for patients with rectal cancer in Stages II and III. Radiation is used to help prevent cancer recurrence. In recent years, doctors have also begun administering chemotherapy and radiation before surgery for rectal cancer (neoadjuvant chemoradiation). The use of radiation before surgery can help shrink the size of the tumor. Pre-operative chemotherapy and radiation may also help preserve sphincter-muscle function and reduce the chance that a patient will need a colostomy.
Side effects of radiation may include:
- Skin irritation around the anus
- Bladder irritation
- Sexual dysfunction in men and vaginal irritation in women