Colon/Rectal Cancer

Colon cancer and rectal cancer have many features in common. They are often referred to together as colorectal cancer.

Colorectal cancer is the third most common cancer (excluding skin cancer) of both men and women in the United States. The ACS estimates that about 153,760 new cases of colon cancer and 41,000 new cases of rectal cancer arediagnosed each year. About 52,000 people die of colorectal cancer each year.

Most colorectal cancers are adenocarcinomas (cancers of the glandular cells that line the inside of the colon and rectum).

Although colorectal cancer is a serious disease, it can be treated successfully by a team of health care professionals. The team may include a gastroenterologist, surgeon, radiation oncologist, medical oncologist, pathologist, oncology nurse, social worker, radiologist, and enterostomal therapist.

About the Colon and Rectum

The colon and rectum are parts of the large intestine, or bowel, which is part of the digestive system. The digestive system processes food for energy and rids the body of solid waste matter.

After food is chewed and swallowed, it travels through the esophagus to the stomach. There it is partly broken down and then sent to the small intestine, also called the small bowel. The small intestine continues breaking down the food and absorbs most of the nutrients.

COLORECTAL CANCER

The most common risk factor is age. Colorectal cancer risk increases with advancing age, peaking at age 67. The most significant risk after age is a family history of colorectal cancer. Colorectal cancer is most common among African Americans and least common among American Indians and Hispanics.

Colorectal cancer, like a number of other diseases, is also related to a high fat diet and lack of exercise.

Relatives of people with colorectal cancer have a higher chance of developing cancer. The risk is 2-3 times higher in a person who has a first degree relative (mother, father, sister or brother) with colon cancer and the closer the relative, the higher the risk.

The small intestine joins the colon, a muscular tube about 5 feet long. The large intestine continues to absorb water and mineral nutrients from the food and stores waste matter, called feces or stool. The waste matter left after this process passes out of the body through the anus. The first 41/2 feet or so of the large intestine is called the colon, and the remainder is the rectum.

The colon has 4 sections. The small intestine is connected to the first of these, called the ascending colon because it extends upward on the right side of the abdomen. The part where the ascending colon joins the small intestine is called the cecum. The second section is called the transverse colon because it goes across the body from the right to the left side. There it joins the third section, the descending colon, which continues onward on the left side. The fourth section is known as the sigmoid colon because of its S-shape. The sigmoid colon joins the rectum, which in turn joins the anus.

The lymphatic system carries fluid throughout the body. Lymph is a clear fluid that contains waste products and immune system cells. Lymphatic vessels carry this fluid to lymph nodes (small, bean-shaped collections of immune system cells important in fighting infections). Most lymphatic vessels of the colon or rectum lead to nearby (regional) lymph nodes. Cancer cells may enter lymph vessels and travel to lymph nodes, where they can continue to grow. If cancer cells grow in these lymph nodes, they are more likely to have spread to other organs of the body as well.

The walls of the colon and rectum are nourished by blood from arteries. After flowing through these body parts, the blood flows into veins. Veins from the colon and rectum lead to the liver and then back to the heart. This pattern of blood flow is important, because cells may break off from a colorectal cancer, enter veins leaving these organs, and travel to the liver. This is why the liver is the most common site of colorectal cancer spread (metastasis).

Colon and Rectal Cancer Work-up (Evaluation) If there is reason to suspect that you have colon or rectal cancer, your doctor will take a complete medical history and do a physical exam. Also, one or more of the following tests will be done to find out if the disease is really present and to determine its stage (how far the cancer has spread).

Medical History and Physical Exam:
When your doctor “takes a history,” he or she will ask you a series of questions about your symptoms and risk factors. Some colorectal cancers may be found because of symptoms such as a change in bowel habits, blood in the stool, weakness or fatigue, abdominal pain, loss of appetite, nausea, weight loss, and straining during a bowel movement. Of course, many non-cancerous (benign) conditions and some other cancers can cause one or more of these symptoms. But if these symptoms are present, a medical evaluation is the only way to determine their cause so that the most appropriate treatment can be chosen. A physical exam for patients thought to have colorectal cancer will include a digital rectal examination (DRE), careful examination of the abdomen to feel for masses or enlarged organs, and a general survey of the rest of the body.

Colonoscopy:
A colonoscope is a long, flexible, lighted tube about the thickness of a finger. It is inserted through the rectum into the colon. A colonoscope allows the doctor, in most cases, to see the entire colon lining. The colonoscope is connected to a video camera and video display monitor so that the doctor can look closely at the inside of your colon. The day before this test you will take strong laxatives to clean out your bowel and on the morning of the test you may also take an enema. A colonoscopy lasts about 15 to 30 minutes and is generally not painful because you are given a mild sedative.

Biopsy:
If a mass or any other abnormal areas are seen through the flexible sigmoidoscope or through the colonoscope, a sample will be taken. A pathologist will examine the sample under a microscope to determine whether it is a cancer or a benign condition. Some abnormalities, such as small polyps, may be entirely removed through a colonoscope. If the abnormal area is large, a biopsy (small tissue sample) is taken. The biopsy sample is usually about 1-inch across and is removed with instruments that are used through the scope.

Blood Counts and Blood Chemistry:
Your doctor will order a blood test that will determine if you have low red blood cell counts (anemia). Many people with colorectal cancer become anemic because of bleeding from the tumor. A blood test will also show how your liver is functioning. Colorectal cancer can spread to the liver and cause changes in blood proteins and enzymes.

Tumor Markers:
Some colon and rectal cancers produce substances such as carcinoembryonic antigen (CEA) that are then released into the bloodstream. Blood tests for these tumor markers are used most often with other tests to watch patients who already have been treated for colorectal cancer. They may provide an early warning that a cancer has returned.

Because the CEA level in the blood can be high for reasons other than cancer or may be normal in a person who has cancer, it is not used to find cancer in people who have never had cancer and appear to be healthy.

Chest x-ray:
This familiar imaging test can often detect colorectal cancer that has spread to the lungs.

Ultrasound:
This imaging test uses a device called a transducer that produces sound waves, which are reflected by nearby body tissues and organs. The pattern of sound wave echoes is detected by the transducer and analyzed by a computer to create an image of the area being studied. Since normal body tissues and tumors reflect sound waves differently, ultrasound is sometimes used to find masses that indicate the cancer has spread. Two special types of ultrasound examinations are used to evaluate people with colon and rectal cancer. Endorectal ultrasound uses a special transducer that can be inserted into the rectum. This test is used to see how far a rectal cancer may have grown and whether it has spread to nearby organs or tissues. Intraoperative ultrasound is done after the surgeon has opened the abdominal cavity. The transducer can be placed against the surface of the liver, making this test very useful in detecting colorectal cancer that has metastasized to the liver.

Computed Tomography:
Commonly referred to as CT or a CAT scan, this test uses a rotating x-ray beam to create a series of pictures of the body from many angles. A computer combines the information from these pictures, producing a detailed cross-sectional image. Contrast material is usually injected into a vein before CT scanning to help produce clearer pictures. A CT scan can often detect colorectal cancer that has spread to internal organs such as the liver, lungs, or elsewhere in the abdomen.

CT-guided Needle Biopsy:
This test is often done if metastasis is suspected. For this test, the patient remains on the CT scanning table while a radiologist places a biopsy needle in the mass. CT scans are repeated until the doctors are confident that the needle is within the mass. A fine needle biopsy sample (tiny fragment of tissue) or a core needle biopsy sample (a thin cylinder of tissue about 1/2-inch long and less than 1/8-inch in diameter) is removed and examined under a microscope.

Magnetic Resonance Imaging:
Like computed tomography, magnetic resonance imaging (MRI or an MRI scan) displays a cross-section of the body. However, MRI uses powerful magnetic fields instead of radiation. The procedure can show cross-sectional views from several angles and is useful in locating metastases from colorectal cancer that are sometimes hard to see on standard x-rays and CT scans. A special MRI can show the doctor more about rectal tumors.

Positron Emission Tomography:
Positron emission tomography (PET or a PET scan) uses glucose (a form of sugar) that contains a radioactive atom. The cancer cells will absorb the glucose and can be detected by a scanner. PET is often useful in identifying cancers that have spread and may be used in patients who have a rising CEA level or suspected metastatic disease that has been indicated by other tests.

Colon and Rectal Cancer Stages

Staging is a process that tells the doctor how widespread the cancer may be – that is, whether the cancer has spread and if so, how far. The stage of a cancer is one of the most important factors in selecting treatment options and predicting outcomes. If you have any questions about your stage, please discuss them with your doctor. A staging system is a standardized way for the cancer care team to describe the extent to which a cancer has spread. This document uses the American Joint Committee on Cancer (AJCC) system, also called the TNM System. This staging system describes the spread of the cancer in relation to the layers of the wall of the colon or rectum, nearby lymph nodes, other organs next to the colon and rectum, and organs farther away.

There are 2 types of AJCC stages. The clinical stage is based on physical examination and some imaging studies done before surgery. The clinical stage is used to decide which, if any, operations should be done for people with colorectal cancer. After colorectal surgery, the pathologic stage is determined by examining the tumor tissue that has been removed. The pathologic stage is used to decide which patients with colon and rectal cancer should receive adjuvant treatment and, if needed, exactly which treatment is best.

The TNM System describes the extent of the primary tumor (T), the absence or presence of metastasis (spread) to nearby lymph nodes (N), and the absence or presence of distant luetastasis (M).

T Categories for Colorectal Cancer
T categories of colorectal cancer describe how far the cancer has spread through the layers that form the wall of the colon and rectum. These layers, from the inner to the outer, include:

• the mucosa (the lining) which includes the muscularis mucosae (a thin layer of muscle tissue beneath the mucosa),
• the submucosa (connective tissue beneath this thin muscle layer),
• the muscularis propria (a thick layer of muscle that contracts to force the contents of the intestines along),
• the subserosa (a thin layer of connective tissue),
• and the serosa (a thin layer that covers the outer surface of some parts of the large intestine).

T’s:
The cancer is in the earliest stage. It has not grown beyond the mucosa (inner layer) of the colon or rectum. This stage is also known as carcinoma in situ or intramucosal carcinoma.

• T1: The cancer has grown through the mucosa and extends into the submucosa.
• T2: The cancer has grown through the mucosa and the submucosa and extends into the thick muscle layer.
• T3: The cancer has grown through the mucosa, the submucosa, and completely through the thick muscle layer. It has spread to the subserosa but not to any nearby organs or tissues.
• T4: The cancer has spread completely through the wall of the colon or rectum into nearby tissues or organs.

N Categories for Colorectal Cancer
The N category describes the cancer spread into nearby lymph nodes.
N0: No lymph node involvement.
N1: Cancer cells found in 1 to 3 regional lymph nodes.
N2: Cancer cells found in 4 or more regional lymph nodes.

M Categories for Colorectal Cancer
The M category describes whether or not there is distant metastasis (spread).
M0: No distant spread.
M1: Distant spread is present.

Types of Treatment for Colon and Rectal Cancers
The 4 main types of treatment for colon and rectal cancer are surgery, radiation therapy, chemotherapy, and immunotherapy. Depending on the stage of the cancer, two or even three of these types of treatment may be combined at the same time or one after another.

After your cancer has been found and staged, your doctor will recommend one or more treatment options. It is important to take time and think about all of your choices.

You may want to ask for a second opinion. This can give you even more information and help you feel more confident about the treatment plan you choose.

Surgery
Colon surgery
Surgery is the main treatment for colon cancer. The usual operation is called a segmental resection or partial colectomy. To prepare for this surgery you will be given laxatives and enemas to clean out your colon. Just before the surgery you will be given general anesthesia, which puts you into a deep sleep. During this surgery, the cancer and a length of normal tissue on either side of the cancer, as well as the nearby lymph nodes are removed. The remaining sections of the colon are then reattached. When you wake up you will have some pain and will be given pain medicine, usually morphine for the first day or two. This operation rarely causes any major permanent problems with digestive functions. Sometimes, a temporary colostomy may be needed. For a colostomy, the colon is attached to the abdominal wall and fecal material drains through an opening in the wall into a bag. Even more rarely, a permanent colostomy may be needed. Your doctor will discuss this with you before your surgery. Patients can usually leave the hospital about 5 to 7 days after surgery and resume usual activities in 6 weeks. Of course, hospitalization and recovery times depend on each patient’s specific medical condition.

It is sometimes possible to remove some very early colon cancers through a colonoscope. When surgery is done this way, the surgeon does not have to cut into the abdomen, which shortens recovery time. Some advanced colon cancers can block the flow of feces. When it is not possible to remove the cancer, the flow of feces can be diverted to a colostomy. (This operation is called a diverting colostomy.) Another alternative is placing a stent (a plastic or metal tube) inside the colon to keep it from becoming blocked if the tumor cannot be removed. If there is blockage, surgery is more likely to lead to complications because the bowel cannot be cleaned with enemas, which helps prevent infection. Also, a complete colonoscopy cannot be done.

It is sometimes possible to remove segments of the colon and nearby lymph nodes through a laparoscope (laparoscopic colectomy). This instrument is a long, lighted viewing tube through which the doctor can operate with special surgical instruments. The viewing tube and instruments are placed into the abdomen through several small surgical incisions. The NCCN guidelines include this procedure as an option. Clinical trials have shown that as a procedure, laparoscopic colectomy works as well as abdominal colectomy.

Rectal Surgery
Several methods are used to remove or destroy rectal cancers. Local resection is an option for some people with stage 1 rectal cancer. It involves cutting through all layers of the rectum to remove invasive cancers as well as some surrounding normal rectal tissue. This surgery can be done through the anus without cutting through the abdomen and it leaves the rectum intact. This procedure is called transanal resection. If your cancer cannot be removed completely by this procedure, transanal resection will not be an option for you. Doctors consider the cancer’s size, its exact location within the rectum, and how far around the circumference of the rectum it extends in order to select which patients should have a local resection.

Many stage 1 and most stage 2 and 3 rectal cancers are removed by either low anterior (LA) resection or abdominoperineal (AP) resection. LA resection is used for cancers near the upper part of the rectum, close to where it connects with the sigmoid colon. After LA resection, the colon is attached to the lower rectum and feces are eliminated in the usual way.

AP resection is used for cancer in the lower part of the rectum, close to its outer connection to the anus. Because the cancer is close to the anus, the anus is also removed. After AP resection, a permanent colostomy is needed. Some patients with stage 4 rectal cancers will need a diverting colostomy. In this operation the surgeon does not remove a rectal cancer that is blocking fecal flow, but instead bypasses the blockage and diverts fecal flow to a colostomy. Some patients may now have a stent (a plastic or metal tube) placed to keep the colon or rectum from becoming blocked if the tumor cannot be removed. Heating the rectal tumor with a laser beam aimed through the anus, called photocoagulation, is another way to relieve or prevent rectal blockage in patients with stage IV cancers.

Surgical Treatment of Colorectal Cancer Metastases
For patients whose colorectal cancer has spread to a few areas in the liver or lungs, removing these metastases can cure the cancer in some instances. Other times, destroying metastases without surgery can help the patient live longer, but not cure them. Liver metastases may also be destroyed by heating them with radio frequency waves (called radio frequency ablation). The radio frequency probe is placed through the skin and guided to the tumor by CT scans or ultrasound images.

Radiation Therapy
Radiation has a major role in treating rectal cancers. Radiation therapy uses high-energy x-rays or particles to kill cancer cells. In treating rectal cancer, radiation treatment is usually given by external beam radiation. External beam radiation is usually given with a linear accelerator, 5 days a week for several weeks. This must be carefully planned, using different imaging techniques, such as a CT scan, so that the beams focus on the cancer and not healthy tissue. Radiation can be given either before surgery (to shrink a tumor so it is easier to remove or to decrease the risk of complications) or after surgery (if there is a risk of the cancer coming back in the tumor area). Chemotherapy with the drug fluorouracil (5FU) may be given by continuous infusion through an intravenous (IV) line (placed in a vein) at the same time as radiation. This drug makes the radiation more effective. Radiation therapy can also be combined with oral capecitabine. Studies have shown that for rectal cancer, radiation along with surgery will often decrease the risk of the cancer coming back (recurrence).

Chemotherapy
Chemotherapy is the use of cancer-fighting drugs injected into a vein or taken by mouth. Chemotherapy is a systemic treatment. The drugs enter the bloodstream and reach all areas of the body, making this treatment useful for cancers that have spread beyond the place they started.

Fluorouracil (5-FU) is the drug most often used to treat colorectal cancer. It is usually given together with other drugs, such as leucovorin, that increase its effectiveness.

5-FU can be given continuously over 2 days as well as by rapid injection on each day. The leucovorin is given on each day over 2 hours. This combination, called the de Gramont regimen, is given every other week.

In some cases, to make the patient respond better to radiation therapy, 5-FU is given as a continuous infusion into a vein. The patient wears a small battery-operated pump that continuously releases 5-FU into an IV line. For patients whose colon or rectal cancer has spread to their liver, chemotherapy drugs may be given directly into the artery that supplies blood to the liver. This approach to treatment of liver metastases is called hepatic artery infusion.

Irinotecan (Camptosar) is another chemotherapy drug that is used with 5-FU. This treatment is called FOLFIRI. It adds irinotecan to the de Gramont 5-FU/leucovorin regimen. Recent studies have shown there may be many side effects when 5-FU, leucovorin, and irinotecan are combined. If this combination of drugs is used, the starting doses may be reduced and your doctor will watch you carefully so that your doses can be adjusted if necessary. If you have a lot of side effects, the dosages may be adjusted.

Oxaliplatin (Eloxatin) is another drug that works well when combined with 5-FU and leucovorin. It may be used instead of irinotecan. Like irinotecan, it is often used with the de Gramont 5-FU/leucovorin regimen. This treatment is called FOLFOX.

Capecitabine (Xeloda), a newer chemotherapy drug given by mouth, is changed to 5-FU once it gets inside the body to the tumor site. This drug can be used instead of intravenous 5-FU and acts as if the 5-FU was being given continuously. Capecitabine can also be combined with radiation therapy.

Immunotherapy
Immunotherapies use natural substances produced by the body’s immune system. These substances may kill cancer cells, slow their growth, or activate the patient’s immune system to fight cancer more effectively.

The immune system produces antibodies to help fight infections. Similar antibodies, called monoclonal antibodies, can be made in the laboratory. Instead of attacking germs as usual antibodies do, some monoclonal antibodies can be designed to attack cancer cells. Three monoclonal antibodies have been approved by the US Food and Drug Administration (FDA) to treat colon or rectal cancer.

The first, bevacizumab (Avastin), works by preventing the growth of new blood vessels that supply tumor cells with the blood, oxygen, and other nutrients they need to grow. Bevacizumab is used with chemotherapy and is likely to be the first treatment used for patients with advanced or metastatic colon or rectal cancer.

The other two monoclonal antibodies, cetuximab (Erbitux) and panitumumab (Vectibix ), work by locking onto a protein on the surface of the tumor cell called epidermal growth factor receptor. This prevents the tumor cell from dividing. Both of these drugs can be used alone as a second or third line treatment for patients with advanced or metastatic colon or rectal cancer. Cetuximab also can be used with irinotecan, either alone or in the FOLFIRI regimen.

Neoadjuvant Treatment and Adjuvant Treatment
The terms neoadjuvant treatment and adjuvant treatment refer to radiation therapy and/or chemotherapy given before (neoadjuvant) or after (adjuvant) surgery.

Neoadjuvant Treatment
The purpose of neoadjuvant treatment is to shrink tumors so that they can be more completely removed by surgery and to help prevent the cancer from coming back in that area. If the tumor in the colon is large or has spread to lymph nodes, chemotherapy may be recommended before surgery. For some rectal tumors, chemotherapy may be combined with radiation therapy before surgery.

Adjuvant Treatment
After surgery, the tissue that has been removed is examined under a microscope to determine the cancer’s stage (how far it has spread). If the cancer is large or has spread to lymph nodes, even though no remaining cancer can be seen, doctors believe it is possible that a few scattered cancer cells may remain in the patient’s body. In this situation more treatment in the form of chemotherapy or radiation therapy may be given.

The following was adapted from the following resources:
1. Cancercare Connect
2.What You Need To Know About Cancer of the Colon and Rectum National Institutes of Health