Rectal Cancer

Rectal bleeding is an early warning sign of rectal cancer.

• Rectal cancer is the growth of abnormal cancerous cells in the lower part of the colon that connects the anus to the large bowel.
• Rectal cancer develops usually over years; its actual cause is not known, but risk factors include increasing age (over 50), smoking, family history, high-fat diet, or a history of polyps or colorectal cancer or inflammatory bowel disease.
• The major symptom of rectal cancer is bleeding from the rectum; other symptoms include anemia, fatigue, shortness of breath, dizziness and/or a fast heartbeat, bowel obstruction, small diameter stools, and weight loss.
• For diagnosis, exams and tests may include fecal occult blood testing, endoscopy, digital rectal examination, sigmoidoscopy, CT/MRI imaging studies, along with routine blood tests and detection of carcinoembryonic antigen (CEA).
• Medical treatment depends on the stage of rectal cancer (stages I-IV), with IV being the most severe stage; multiple chemotherapy medications are available and are chosen by the specialist (oncologist) to fit the individual's stage of rectal cancer; other specialists may need to be consulted.
• Surgery is used to both treat and reduce symptoms and, in some individuals, may result in a remission of the cancer.
• Radiation therapy is also used to kill or shrink rectal cancers.
• Follow-up is important to make sure that rectal cancer does not recur.
• Prevention involves detection and removal of precancerous growths.
• The outlook or prognosis for individuals with rectal cancer is usually related to the stage of cancer, with stages III and IV having the poorest outcomes.

The rectum is the lower part of the colon that connects the large bowel to the anus. The rectum's primary function is to store formed stool in preparation for evacuation. Like the colon, the three layers of the rectal wall are as follows:

• Mucosa: This layer of the rectal wall lines the inner surface. The mucosa is composed of glands that secrete mucus to help the passage of stool.
• Muscularis propria: This middle layer of the rectal wall is composed of muscles that help the rectum keep its shape and contract in a coordinated fashion to expel stool.
• Mesorectum: This fatty tissue surrounds the rectum.

In addition to these three layers, another important component of the rectum is the surrounding lymph nodes (also called regional lymph nodes). Lymph nodes are part of the immune system and assist in conducting surveillance for harmful materials (including viruses and bacteria) that may be threatening the body. Lymph nodes surround every organ in the body, including the rectum.

The American Cancer Society (ACS) estimates about 95,520 new cases of colon cancer, and 39,910 new cases of rectal cancer will occur in 2017. Males are more likely than females to develop rectal cancer (about 23,720 males to 16,190 females in 2017). The most common type of rectal cancer is adenocarcinoma (98%), which is cancer arising from the mucosa. Cancer cells can also spread from the rectum to the lymph nodes on their way to other parts of the body.

Like colon cancer, the prognosis and treatment of rectal cancer depend on how deeply the cancer cells have invaded the rectal wall and surrounding lymph nodes (its stage, or extent of spread). However, although the rectum is part of the colon, the location of the rectum in the pelvis poses additional challenges in treatment when compared with colon cancer.

This article only discusses issues related to rectal adenocarcinoma.

Rectal cancer usually develops over several years, first growing as a precancerous growth called a polyp. Some polyps have the ability to turn into cancer and begin to grow and penetrate the wall of the rectum. The actual cause of rectal cancer is unclear. However, the following are risk factors for developing rectal cancer:

• Advancing age
• Smoking
• Family history of colon or rectal cancer
• High-fat diet and/or a diet mostly from animal sources (a diet usually found in developed countries such as the United States)
• Personal or family history of polyps or colorectal cancer
• Inflammatory bowel disease

Family history is a factor in determining the risk of rectal cancer. If a family history of colorectal cancer is present in a first-degree relative (a parent or a sibling), then endoscopy of the colon and rectum should begin 10 years before the age of the relative's diagnosis or at age 50 years, whichever comes first.

An often forgotten risk factor, but perhaps the most important, is the lack of screening for rectal cancer. Routine cancer screening of the colon and rectum is the best way to prevent rectal cancer.

Genetics may play a role as Lynch syndrome, an inherited disorder also known as hereditary nonpolyposis colorectal cancer or HNPCC, increases the risk of many cancers, including rectal.

Although human papillomavirus (HPV) infections are more related to anal cancer and squamous cell cancers around the anus and anal canal, some studies show that they can also be related to rectal cancer.

Because some rectal cancers may be associated with HPV infections, it may be possible that HPV vaccination could reduce the chance of getting some rectal cancers.

Rectal cancer can cause many symptoms and signs that require a person to seek medical care. However, rectal cancer may also be present without any symptoms, underscoring the importance of routine health screening. Symptoms and signs to be aware of include the following:

• Bleeding (the most common symptom; present in about 80% of individuals with rectal cancer)
• Seeing blood mixed with stool is a sign to seek immediate medical care. Although many people bleed due to hemorrhoids, a doctor should still be notified in the event of rectal bleeding.
• Change in bowel habits (more gas or excessive amounts of gas, smaller stools, diarrhea)
• Prolonged rectal bleeding (perhaps in small quantities that are not seen in the stool) may lead to anemia, causing fatigue, shortness of breath, lightheadedness, or a fast heartbeat.
• Bowel obstruction. A rectal mass may grow so large that it prevents the normal passage of stool. This blockage may lead to the feeling of severe constipation or pain when having a bowel movement. In addition, abdominal pain, discomfort, or cramping may occur due to the blockage.
• Stool size may appear narrow so that it can be passed around the rectal mass. Therefore, pencil-thin or narrow stools may be another sign of obstruction from rectal cancer.
• A person with rectal cancer may have a sensation that the stool cannot be completely evacuated after a bowel movement.
• Cancer may cause weight loss. Unexplained weight loss (in the absence of dieting or a new exercise program) requires a medical evaluation.

Note that sometimes hemorrhoids (swollen veins in the anal area) can mimic the pain, discomfort, and bleeding seen with anal-rectal cancers. Individuals who have the above symptoms should get a medical exam of their anal-rectal area to be sure they have an accurate diagnosis.

If a person has been diagnosed with rectal cancer, the doctor should be asked the following questions:

• Where is my cancer located?
• How far has the cancer spread? (What is the stage of the cancer?)
• What treatment options do I have?
• What is the overall goal of treatment in my case?
• What are the risks and side effects of the proposed treatment?
• Am I eligible for a clinical trial?
• How do I find out if I am eligible for a clinical trial?

Depending on the extent or progression of the disease, specialists such as emergency-medicine specialists, pathologists, gastroenterologists, oncologists, radiologists, and surgeons may be consulted.

Appropriate colorectal screening leading to the detection and removal of precancerous growths is the only way to prevent this disease. Screening tests for rectal cancer include the following:

• Fecal occult blood test (FOBT) or fecal immunochemical tests (FIT): Early rectal cancer may damage blood vessels of the rectal lining and cause small amounts of blood to leak into the feces. The stool appearance may not change. The fecal occult blood test requires placing a small amount of stool on a special paper that is provided by a doctor. The doctor then applies a chemical to that paper to see if blood is present in the stool sample. Statistics suggest the tests are 95% accurate (positive) in patients with rectal cancer. However, the test may also be positive in some benign conditions as well.
• Endoscopy: During endoscopy, a doctor inserts a flexible tube with a camera at the end (called an endoscope) through the anus and into the rectum and colon. During this procedure, the doctor can see and remove abnormalities on the inner lining of the colon and rectum.

If rectal cancer is suspected, the tumor can be physically detected through either digital rectal examination (DRE) or endoscopy.

• A digital rectal examination is performed by a doctor using a lubricated gloved finger inserted through the anus to feel the cancer on the rectal wall. Not all rectal cancers can be felt this way, and detection is dependent on how far the tumor is from the anus. If an abnormality is detected by a digital rectal examination, then an endoscopy is performed for further evaluation of the cancer.
• Flexible sigmoidoscopy is the insertion of a flexible tube with a camera on the end (called an endoscope) through the anus and into the rectum. An endoscope allows a doctor to see the entire rectum, including the lining of the rectal wall.
• Rigid sigmoidoscopy is the insertion of a rigid optical scope inserted through the anus and into the rectum. Rigid sigmoidoscopy is usually performed by either a gastroenterologist or a surgeon. The advantage of rigid sigmoidoscopy is that a more exact measurement of the tumor's distance from the anus can be obtained, which may be relevant if surgery is required.
• A colonoscopy may be performed. For a colonoscopy, a flexible endoscope is inserted through the anus and into the rectum and colon. A colonoscopy allows a doctor to see abnormalities in the entire colon, including the rectum.

Because the depth of cancer growth into the rectal wall is important in determining treatment, an endoscopic ultrasound (EUS) may be performed during endoscopy. An endoscopic ultrasound uses an ultrasound probe at the tip of an endoscope that allows a doctor to see how deeply the cancer has penetrated. In addition, a doctor can measure the size of the lymph nodes around the rectum during an endoscopic ultrasound. Based on the size of the lymph nodes, a good prediction can be made as to whether the cancer has spread to the lymph nodes.

Once an abnormality is seen with endoscopy, a biopsy specimen is obtained using the endoscope and sent to a pathologist. The pathologist can confirm that the abnormality is a cancer and needs treatment. A person may experience small amounts of bleeding after a biopsy is performed. If this bleeding is heavy or lasts longer than a few days, a doctor should be notified immediately. A chest X-ray and a CT scan of the chest, abdomen, and pelvis are most likely performed to see whether the cancer has spread further than the rectum or surrounding lymph nodes. MRI is also used to determine the extent of spread of the cancer.

Routine blood studies (for example, CBC, liver function tests, B-12 levels) are performed to assess how a person might tolerate the upcoming treatment.

In addition, a blood test called CEA (carcinoembryonic antigen) is obtained. CEA is often produced by colorectal cancers and can be a useful gauge of how the treatment is working. After the treatment, the doctor may regularly check the CEA level as one indicator of whether the cancer has returned. However, checking the CEA level is not an absolute test for colorectal cancers, and other conditions may cause a rise in the CEA level. Likewise, a normal CEA level is not a guarantee that the cancer is no longer present. Also, a cancer antigen (CA) 19-9 assay may be used to monitor the disease.

The treatment and prognosis of rectal cancer depend on the stage of the cancer, which is determined by the following three considerations:

• How deeply the tumor has invaded the wall of the rectum
• Whether the lymph nodes appear to have cancer in them
• Whether the cancer has spread to any other locations in the body (Organs that rectal cancer commonly spreads to include the liver and the lungs.)

There are several ways to stage rectal cancer; Duke's classification (the first system to stage rectal cancers), Stage system I-IV, and the TNM classification (TNM represents T, the location of the tumor; N, the nodes [lymph nodes] invaded by tumor cells, and M, metastasis of tumor cells to other organs). The TNM classification is very detailed; many doctors choose to use the more simplified I-IV stages. This article will present this system. In general, all the classifications or stage systems describe the same process of cancer development.

The stages of rectal cancer are as follows:

• Stage I: The tumor involves only the first or second layer of the rectal wall, and no lymph nodes are involved.
• Stage II: The tumor penetrates into the mesorectum, but no lymph nodes are involved.
• Stage III: Regardless of how deeply the tumor penetrates, the lymph nodes are involved with the cancer (this stage can be divided into IIIa, IIIb, and IIIc, depending how far the cancer has grown through rectal tissue or through its wall).
• Stage IV: Convincing evidence of the cancer exists in other parts of the body, outside of the rectal area.

Localized rectal cancer includes stages I-III. Metastatic rectal cancer is stage IV. The goals of treating localized rectal cancer are to ensure the removal of all the cancer and to prevent a recurrence of the cancer, either near the rectum or elsewhere in the body.

Surgery is likely to be the only necessary step in treatment if stage I rectal cancer is diagnosed.

The risk of the cancer coming back after surgery is low, and therefore, chemotherapy is not usually offered. Sometimes, after the removal of a tumor, the doctor discovers that the tumor penetrated into the mesorectum (stage II) or that the lymph nodes contained cancer cells (stage III). In these individuals, chemotherapy and radiation therapy are offered after recovery from the surgery to reduce the chance of the cancer returning. Chemotherapy and radiation therapy given after surgery is called adjuvant therapy.

If the initial exams and tests show a person to have stage II or III rectal cancer, then chemotherapy and radiation therapy should be considered before surgery. Chemotherapy and radiation given before surgery is called neoadjuvant therapy. This therapy lasts approximately six weeks. Neoadjuvant therapy is performed to shrink the tumor so it can be more completely removed by surgery. In addition, a person is likely to tolerate the side effects of combined chemotherapy and radiation therapy better if this therapy is administered before surgery rather than afterward.

After recovery from the surgery, a person who has undergone neoadjuvant therapy should meet with the oncologist to discuss the need for more chemotherapy. If the rectal cancer is metastatic, then surgery and radiation therapy would only be performed if persistent bleeding or bowel obstruction from the rectal mass exist. Otherwise, chemotherapy alone is the standard treatment of metastatic rectal cancer.

At this time, metastatic rectal cancer is not curable. However, average survival times for people with metastatic rectal cancer have lengthened over the past several years because of the introduction of new medications.

The following chemotherapy drugs may be used at various points during therapy:

• 5-Fluorouracil (5-FU): This drug is given intravenously either as a continuous infusion using a medication pump or as quick injections on a routine schedule. This drug has direct effects on the cancer cells and is often used in combination with radiation therapy because it makes cancer cells more sensitive to the effects of radiation. Side effects include fatigue, diarrhea, mouth sores, and hand, foot, and mouth syndrome (redness, peeling, and pain in the palms of the hands and the soles of the feet).
• Capecitabine (Xeloda): This drug is given orally and is converted by the body to a compound similar to 5-FU. Capecitabine has similar effects on cancer cells as 5-FU and can be used either alone or in combination with radiation therapy. Side effects are similar to intravenous 5-FU.
• Leucovorin (Wellcovorin): This drug increases the effects of 5-FU and is usually administered just prior to 5-FU administration.
• Oxaliplatin (Eloxatin): This drug is given intravenously once every two or three weeks. Oxaliplatin has recently become the most common drug to use in combination with 5-FU for the treatment of metastatic rectal cancer. Side effects include fatigue, nausea, increased risk of infection, anemia, and peripheral neuropathy (tingling or numbness of the fingers and toes). This drug may also cause a temporary sensitivity to cold temperatures up to two days after administration. Inhaling cold air or drinking cold liquids should be avoided if possible after receiving oxaliplatin.
• Irinotecan (Camptosar, CPT-11): This drug is given intravenously once every one to two weeks. Irinotecan is also commonly combined with 5-FU. Side effects include fatigue, diarrhea, increased risk of infection, and anemia. Because both irinotecan and 5-FU cause diarrhea, this symptom can be severe and should be reported immediately to a doctor.
• Bevacizumab (Avastin): This drug is given intravenously once every two to three weeks. Bevacizumab is an antibody to vascular endothelial growth factor (VEGF) and is given to reduce blood flow to the cancer. Bevacizumab is used in combination with 5-FU and irinotecan or oxaliplatin for the treatment of metastatic rectal cancer. Side effects include high blood pressure, nose bleeding, blood clots, and bowel perforation.
• Cetuximab (Erbitux): This drug is given intravenously once every week. Cetuximab is an antibody to epidermal growth factor receptor (EGFR) and is given because rectal cancer has large amounts of EGFR on the cell surface. Cetuximab is used alone or in combination with irinotecan for the treatment of metastatic rectal cancer. Side effects include an allergic reaction to the medication and an acne-like rash on the skin. Clinical trials are underway to evaluate this antibody for the treatment of localized rectal cancer.
• Vincristine (Vincasar PFS, Oncovin): The mechanism of action of this drug is not fully known; is known to inhibit cell division.
• Panitumumab (Vectibix): This recombinant monoclonal antibody binds to human epidermal growth factor receptor (EGFR) and is used to treat colorectal cancer that has metastasized after chemotherapy treatment.

Medications are available to alleviate the side effects of chemotherapy and antibody treatments. If side effects occur, an oncologist should be notified so that they can be addressed promptly.

Home remedies do not treat rectal cancers, but some may help a patient manage side effects of the disease and treatment. For example, ginger tea may help reduce nausea and vomiting while salty crackers and sips of water may reduce diarrhea. However, patients are urged to discuss any home remedies with their doctors before using them.

Surgical removal of a tumor and/or rectum removal is the cornerstone of curative therapy for localized rectal cancer. In addition to removing the rectal tumor, removing the fat and lymph nodes in the area of a rectal tumor is also necessary to minimize the chance that any cancer cells might be left behind.

However, rectal surgery can be difficult because the rectum is in the pelvis and is close to the anal sphincter (the muscle that controls the ability to hold stool in the rectum). With more deeply invading tumors and when the lymph nodes are involved, chemotherapy and radiation therapy are usually included in the treatment course to increase the chance that all microscopic cancer cells are removed or killed.

Four types of surgeries are possible, depending on the location of the tumor in relation to the anus.

• Transanal excision: If the tumor is small, located close to the anus, and confined only to the mucosa (innermost layer), then performing a transanal excision, where the tumor is removed through the anus, may be possible. No lymph nodes are removed with this procedure. No incisions are made on the skin.
• Mesorectal surgery: This surgical procedure involves the careful dissection of the tumor from the healthy tissue. Mesorectal surgery is being performed mostly in Europe.
• Low anterior resection (LAR): When the cancer is in the upper part of the rectum, then a low anterior resection is performed. This surgical procedure requires an abdominal incision, and the lymph nodes are typically removed along with the segment of the rectum containing the tumor. The two ends of the colon and rectum that are left behind can be joined, and normal bowel function can resume after surgery.
• Abdominoperineal resection (APR): If the tumor is located close to the anus (usually within 5 cm), performing an abdominoperineal resection and removing the anal sphincter may be necessary. Lymph nodes are also removed (lymphadenectomy) during this procedure. With an abdominoperineal resection, a colostomy is necessary. A colostomy is an opening of the colon to the front of the abdomen, where feces are eliminated into a bag.

Radiation therapy uses high-energy rays that are aimed at the cancer cells to kill or shrink them. For rectal cancer, radiation therapy may be used either before surgery (neoadjuvant therapy) or after surgery (adjuvant therapy), usually in conjunction with chemotherapy.

The goals of radiation therapy are as follows:

• Shrink the tumor to make its surgical removal easier (if given before surgery).
• Kill the remaining cancer cells after surgery to reduce the risk of the cancer returning or spreading.
• Treat any local recurrences that are causing symptoms, such as abdominal pain or bowel obstruction.

Typically, radiation treatments are given daily, five days a week, for up to six weeks. Each treatment lasts only a few minutes and is completely painless; it is similar to having an X-ray film taken.

The main side effects of radiation therapy for rectal cancer include mild skin irritation, diarrhea, rectal or bladder irritation, and fatigue. These side effects usually resolve soon after the treatment is complete.

Chemotherapy and radiation are often given for stages II and III rectal cancer. Preoperative chemotherapy and radiation are sometimes performed to decrease the size of the tumor.

Because a risk exists of rectal cancer coming back after treatment, routine follow-up care is necessary. Follow-up care usually consists of regular visits to the doctor's office for physical exams, blood studies, and imaging studies. In addition, a colonoscopy is recommended one year after a diagnosis of rectal cancer. If the findings from the colonoscopy are normal, then the procedure can be repeated every three years.

Appropriate colorectal screening leading to the detection and removal of precancerous growths is the only way to prevent this disease. Screening tests for rectal cancer include fecal occult blood test and endoscopy.

If a family history of colorectal cancer is present in a first-degree relative (a parent or a sibling), then endoscopy of the colon and rectum should begin 10 years before the age of the relative's diagnosis or at age 50 years, whichever comes first.

The outlook for recovery from rectal cancer is unique for each individual. Many factors are involved when considering the chance of survival after rectal cancer treatment.

Long-term survival generally depends upon the stage of the cancer at the time of diagnosis and treatment.

According to the stage, the following approximations of the likelihood of survival (life expectancy) five years after treatment are as follows:

• Stage I: The probability of being alive in five years is approximately 70%-80%.
• Stage II: The probability of being alive in five years is approximately 50%-60%.
• Stage III: The probability of being alive in five years is approximately 30%-40%.
• Stage IV: The probability of being alive in five years is less than 10%.

These life expectancy estimates vary depending on the way groups of doctors calculate the statistics.

Being diagnosed with cancer is a physically and emotionally trying experience. Many avenues of support exist within the local community and beyond, both for people diagnosed with cancer and for their family and friends. The American Cancer Society provides information on local support groups. In addition, social workers, counselors, psychiatrists, and clergy can also be helpful in providing information and companionship through the difficult times caused by a cancer diagnosis.

American Cancer Society
(800) ACS-2345 (227-2345)

National Cancer Institute
NCI Public Inquiries Office
6116 Executive Boulevard, Room 3036A
Bethesda, MD 20892-8322
(800) 4-Cancer (422-6237)

People Living with Cancer
American Society of Clinical Oncology
1900 Duke Street, Suite 200
Alexandria, VA 22314
703-797-1914

U.S. National Institutes of Health, National Cancer Institute, Colon and Rectal Cancer

U.S. National Institutes of Health, National Cancer Institute, Clinical Trials