Anal Cancer

  • Dana-Farber/Brigham and Women's Cancer Care

    Anal cancer is a type of cancer that forms in tissues of the anus. The anus is the opening of the rectum to the outside of the body. Learn about anal cancer and find information on how we support and care for people with anal cancer before, during, and after treatment.

Treatment 

At the Center for Gastrointestinal Oncology, we view every patient as an individual, with unique needs and expectations. This understanding guides us in creating a tailored, personalized treatment plan that takes your lifestyle and goals into account.

Our team of specialists includes medical oncologists, surgeons, and radiation oncologists who focus exclusively on gastrointestinal cancers, including colon cancer, pancreatic cancer, stomach cancer, liver cancer, neuroendocrine cancer, thyroid cancer, and esophageal cancer.

We offer the most advanced treatments for gastrointestinal cancers, including access to clinical trials. As a new patient, you'll have your tumors tested for molecular alterations, the results of which will help form the basis of your therapy.

We understand that cancer treatment can be challenging both physically and emotionally. Our patients, and their families, have access to a range of support services, including nutrition counseling, rehabilitation and  physical therapy, support groups, and complementary therapies such as acupuncture and massage.

Learn more about treatment and support for patients with gastrointestinal cancer 

Our clinicians are experts in treating all types of gastrointestinal cancers, including: 

  • Anal cancer
  • Bile duct cancer
  • Colon cancer
  • Esophageal cancer
  • Gastrointestinal carcinoid tumor
  • Primary liver cancer
  • Small intestine cancer
  • Stomach/gastric cancer
  • Stomach carcinoid tumor
  • Cholangiocarcinoma
  • Duodenal cancer
  • Pancreatic cancer
  • Rectal cancer
  • Islet cell cancer
  • Liver cancer
  • Small bowel cancer

Contact us 

New patients 

If you have never been seen before at Dana-Farber/Brigham and Women's Cancer Center, please call 877-442-3324 or use this online form to make an appointment.

If you are a current patient, please call the center’s main number at 617-632-4500.

To schedule an appointment in the Gastrointestinal Cancer Risk and Prevention Clinic, call 617-632-2178.

Mailing address
Center for Gastrointestinal Oncology
Dana-Farber Cancer Institute
450 Brookline Ave.
Boston, MA 02215-5450

Information for: Patients | Healthcare Professionals

General Information About Anal Cancer

Anal cancer is a disease in which malignant (cancer) cells form in the tissues of the anus.

The anus is the end of the large intestine, below the rectum, through which stool (solid waste) leaves the body. The anus is formed partly from the outer skin layers of the body and partly from the intestine. Two ring-like muscles, called sphincter muscles, open and close the anal opening and let stool pass out of the body. The anal canal, the part of the anus between the rectum and the anal opening, is about 1½ inches long.

Gastrointestinal (digestive) system anatomy; shows esophagus, liver, stomach, colon, small intestine, rectum, and anus. 
Anatomy of the lower digestive system, showing the colon and other organs.

 

The skin around the outside of the anus is called the perianal area. Tumors in this area are skin tumors, not anal cancer.

Being infected with the human papillomavirus (HPV) increases the risk of developing anal cancer.

Risk factors include the following:

  • Being infected with human papillomavirus (HPV).
  • Having many sexual partners.
  • Having receptive anal intercourse (anal sex).
  • Being older than 50 years.
  • Frequent anal redness, swelling, and soreness.
  • Having anal fistulas (abnormal openings).
  • Smoking cigarettes.

Signs of anal cancer include bleeding from the anus or rectum or a lump near the anus.

These and other signs and symptoms may be caused by anal cancer or by other conditions. Check with your doctor if you have any of the following:

  • Bleeding from the anus or rectum.
  • Pain or pressure in the area around the anus.
  • Itching or discharge from the anus.
  • A lump near the anus.
  • A change in bowel habits.

Tests that examine the rectum and anus are used to detect (find) and diagnose anal cancer.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Digital rectal examination (DRE): An exam of the anus and rectum. The doctor or nurse inserts a lubricated, gloved finger into the lower part of the rectum to feel for lumps or anything else that seems unusual.
    Digital rectal exam; drawing shows a side view of the male reproductive and urinary anatomy, including the prostate, rectum, and bladder; also shows a gloved and lubricated finger inserted into the rectum to feel the prostate. 
    Digital rectal exam (DRE). The doctor inserts a gloved, lubricated finger into the rectum and feels the prostate to check for anything abnormal.
  • Anoscopy: An exam of the anus and lower rectum using a short, lighted tube called an anoscope.
  • Proctoscopy: An exam of the rectum using a short, lighted tube called a proctoscope.
  • Endo-anal or endorectal ultrasound: A procedure in which an ultrasound transducer (probe) is inserted into the anus or rectum and used to bounce high-energy sound waves (ultrasound) off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram.
  • Biopsy: The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer. If an abnormal area is seen during the anoscopy, a biopsy may be done at that time.

Certain factors affect the prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) depends on the following:

  • The size of the tumor.
  • Where the tumor is in the anus.
  • Whether the cancer has spread to the lymph nodes.

The treatment options depend on the following:

  • The stage of the cancer.
  • Where the tumor is in the anus.
  • Whether the patient has human immunodeficiency virus (HIV).
  • Whether cancer remains after initial treatment or has recurred.

Stages of Anal Cancer

After anal cancer has been diagnosed, tests are done to find out if cancer cells have spread within the anus or to other parts of the body.

The process used to find out if cancer has spread within the anus or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests may be used in the staging process:

  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, such as the abdomen or chest, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography. For anal cancer, a CT scan of the pelvis and abdomen may be done.
  • Chest x-ray: An x-ray of the organs and bones inside the chest. An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • PET scan (positron emission tomography scan): A procedure to find malignanttumorcells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if anal cancer spreads to the lung, the cancer cells in the lung are actually anal cancer cells. The disease is metastatic anal cancer, not lung cancer.

The following stages are used for anal cancer:

Stage 0 (Carcinoma in Situ)

In stage 0, abnormalcells are found in the innermost lining of the anus. These abnormal cells may become cancer and spread into nearby normal tissue. Stage 0 is also called carcinoma in situ.

Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime  
Pea, peanut, walnut, and lime show tumor sizes.

Stage I

In stage I, cancer has formed and the tumor is 2 centimeters or smaller.

Stage II

In stage II, the tumor is larger than 2 centimeters.

Stage IIIA

In stage IIIA, the tumor may be any size and has spread to either:

  • lymph nodes near the rectum; or
  • nearby organs, such as the vagina, urethra, and bladder.

Stage IIIB

In stage IIIB, the tumor may be any size and has spread:

  • to nearby organs and to lymph nodes near the rectum; or
  • to lymph nodes on one side of the pelvis and/or groin, and may have spread to nearby organs; or
  • to lymph nodes near the rectum and in the groin, and/or to lymph nodes on both sides of the pelvis and/or groin, and may have spread to nearby organs.

Stage IV

In stage IV, the tumor may be any size and cancer may have spread to lymph nodes or nearby organs and has spread to distant parts of the body.

Recurrent Anal Cancer

Recurrentanal cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the anus or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with anal cancer.

Different types of treatments are available for patients with anal cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Three types of standard treatment are used:

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, or a body cavity such as the abdomen, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Surgery

  • Localresection: A surgical procedure in which the tumor is cut from the anus along with some of the healthy tissue around it. Local resection may be used if the cancer is small and has not spread. This procedure may save the sphincter muscles so the patient can still control bowel movements. Tumors that form in the lower part of the anus can often be removed with local resection.
  • Abdominoperineal resection: A surgical procedure in which the anus, the rectum, and part of the sigmoid colon are removed through an incision made in the abdomen. The doctor sews the end of the intestine to an opening, called a stoma, made in the surface of the abdomen so body waste can be collected in a disposable bag outside of the body. This is called a colostomy. Lymph nodes that contain cancer may also be removed during this operation.
    Three-panel drawing showing anal cancer surgery with colostomy; first panel shows area of anus with cancer, middle panel shows cancer and nearby tissue removed and stoma created, last panel shows a colostomy bag attached to the stoma. 
    Resection of the colon with colostomy. Part of the colon containing the cancer and nearby healthy tissue are removed, a stoma is created, and a colostomy bag is attached to the stoma.

Having the human immunodeficiency virus can affect treatment of anal cancer.

Cancer therapy can further damage the already weakened immune systems of patients who have the human immunodeficiency virus (HIV). For this reason, patients who have anal cancer and HIV are usually treated with lower doses of anticancer drugs and radiation than patients who do not have HIV.

New types of treatment are being tested in clinical trials.

This summary section describes treatments that are being studied in clinical trials. It may not mention every new treatment being studied. Information about clinical trials is available from the NCI Web site.

Radiosensitizers

Radiosensitizers are drugs that make tumor cells more sensitive to radiation therapy. Combining radiation therapy with radiosensitizers may kill more tumor cells.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

Treatment Options by Stage

Stage 0 (Carcinoma in Situ)

Treatment of stage 0 is usually localresection.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 anal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage I Anal Cancer

Treatment of stage I anal cancer may include the following:

  • Localresection.
  • External-beam radiation therapy with or without chemotherapy. If cancer remains after treatment, more chemotherapy and radiation therapy may be given to avoid the need for a permanent colostomy.
  • Internal radiation therapy.
  • Abdominoperineal resection, if cancer remains or comes back after treatment with radiation therapy and chemotherapy.
  • Internal radiation therapy for cancer that remains after treatment with external-beam radiation therapy.

Patients who have had treatment that saves the sphincter muscles may receive follow-up exams every 3 months for the first 2 years, including rectal exams with endoscopy and biopsy, as needed.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I anal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage II Anal Cancer

Treatment of stage II anal cancer may include the following:

  • Localresection.
  • External-beam radiation therapy with chemotherapy. If cancer remains after treatment, more chemotherapy and radiation therapy may be given to avoid the need for a permanent colostomy.
  • Internal radiation therapy.
  • Abdominoperineal resection, if cancer remains or comes back after treatment with radiation therapy and chemotherapy.
  • A clinical trial of new treatment options.

Patients who have had treatment that saves the sphincter muscles may receive follow-up exams every 3 months for the first 2 years, including rectal exams with endoscopy and biopsy, as needed.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II anal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IIIA Anal Cancer

Treatment of stage IIIA anal cancer may include the following:

  • External-beam radiation therapy with chemotherapy. If cancer remains after treatment, more chemotherapy and radiation therapy may be given to avoid the need for a permanent colostomy.
  • Internal radiation therapy.
  • Abdominoperineal resection, if cancer remains or comes back after treatment with chemotherapy and radiation therapy.
  • A clinical trial of new treatment options.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIIA anal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IIIB Anal Cancer

Treatment of stage IIIB anal cancer may include the following:

  • External-beam radiation therapy with chemotherapy.
  • Localresection or abdominoperineal resection, if cancer remains or comes back after treatment with chemotherapy and radiation therapy. Lymph nodes may also be removed.
  • A clinical trial of new treatment options.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIIB anal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IV Anal Cancer

Treatment of stage IV anal cancer may include the following:

  • Surgery as palliative therapy to relieve symptoms and improve the quality of life.
  • Radiation therapy as palliative therapy.
  • Chemotherapy with radiation therapy as palliative therapy.
  • A clinical trial of new treatment options.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV anal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Anal Cancer

Treatment of recurrentanal cancer may include the following:

  • Radiation therapy and chemotherapy, for recurrence after surgery.
  • Surgery, for recurrence after radiation therapy and/or chemotherapy.
  • A clinical trial of radiation therapy with chemotherapy and/or radiosensitizers.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent anal cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Anal Cancer

For more information from the National Cancer Institute about anal cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on February 7, 2014.


General Information About Anal Cancer

Incidence and Mortality

Estimated new cases and deaths from anal, anal canal, and anorectal cancer in the United States in 2014:[1]

  • New cases: 7,210.
  • Deaths: 950.

Prognosis and Survival

Anal cancer is usually curable. The three major prognostic factors are site (anal canal vs. perianal skin), size (primary tumors <2 cm in size have better prognoses), and nodal status.

Anal cancer is an uncommon malignancy and accounts for only a small percentage (4%) of all cancers of the lower alimentary tract. Clinical trials such as EST-7283R, for example, have evaluated the roles of chemotherapy, radiation therapy, and surgery in the treatment of this disease.[2][3] Information about ongoing clinical trials is available from the NCI Web site.

Risk Factors

Overall, the risk of anal cancer is rising with data suggesting that persons engaging in certain sexual practices, such as receptive anal intercourse, or persons with a high lifetime number of sexual partners are at an increased risk of anal cancer. These practices may have led to an increase in the number of individuals at risk for infection with human papillomavirus (HPV); HPV infection is strongly associated with anal cancer development and may be a necessary step in its carcinogenesis.[4][5][6][7]

References:

  1. American Cancer Society: Cancer Facts and Figures 2014. Atlanta, Ga: American Cancer Society, 2014. Available online. Last accessed May 21, 2014.

  2. Martenson JA, Lipsitz SR, Lefkopoulou M, et al.: Results of combined modality therapy for patients with anal cancer (E7283). An Eastern Cooperative Oncology Group study. Cancer 76 (10): 1731-6, 1995.

  3. Fuchshuber PR, Rodriguez-Bigas M, Weber T, et al.: Anal canal and perianal epidermoid cancers. J Am Coll Surg 185 (5): 494-505, 1997.

  4. Johnson LG, Madeleine MM, Newcomer LM, et al.: Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer 101 (2): 281-8, 2004.

  5. Daling JR, Weiss NS, Hislop TG, et al.: Sexual practices, sexually transmitted diseases, and the incidence of anal cancer. N Engl J Med 317 (16): 973-7, 1987.

  6. Palefsky JM, Holly EA, Gonzales J, et al.: Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer. Cancer Res 51 (3): 1014-9, 1991.

  7. Ryan DP, Compton CC, Mayer RJ: Carcinoma of the anal canal. N Engl J Med 342 (11): 792-800, 2000.

Cellular Classification of Anal Cancer

Squamous cell (epidermoid) carcinomas make up the majority of all primary cancers of the anus. The important subset of cloacogenic (basaloid transitional cell) tumors constitutes the remainder. These two histologic variants are associated with human papillomavirus infection.[1] Adenocarcinomas from anal glands or fistulae formation and melanomas are rare. Treatment of anal melanoma is not included in this summary.

References:

  1. Palefsky JM, Holly EA, Gonzales J, et al.: Detection of human papillomavirus DNA in anal intraepithelial neoplasia and anal cancer. Cancer Res 51 (3): 1014-9, 1991.

Stage Information for Anal Cancer

The anal canal extends from the rectum to the perianal skin and is lined by a mucous membrane that covers the internal sphincter. The following is a staging system for anal canal cancer that has been described by the American Joint Committee on Cancer (AJCC) and the International Union Against Cancer.[1] Tumors of the anal margin (below the anal verge and involving the perianal hair-bearing skin) are classified with skin tumors.

Definitions of TNM

The following is a staging system for anal canal cancer that has been described by the AJCC and the International Union Against Cancer.[1]

Table 1. Primary Tumor (T)a

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

Tis

Carcinoma in situ (i.e., Bowen disease, high-grade squamous intraepithelial lesion, and anal intraepithelial neoplasia II–III.)

T1

Tumor ≤2 cm in greatest dimension.

T2

Tumor >2 cm but ≤5 cm in greatest dimension.

T3

Tumor >5 cm in greatest dimension.

T4

Tumor of any size invades adjacent organ(s), e.g., vagina, urethra, and bladder.b

aReprinted with permission from AJCC: Anus. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 165-73.

bDirect invasion of the rectal wall, perirectal skin, subcutaneous tissue, or the sphincter muscle(s) is not classified as T4.

Table 2. Regional Lymph Nodes (N)a

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Metastases in perirectal lymph node(s).

N2

Metastases in unilateral internal iliac and/or inguinal lymph node(s).

N3

Metastases in perirectal and inguinal lymph nodes and/or bilateral internal iliac and/or inguinal lymph nodes.

aReprinted with permission from AJCC: Anus. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 165-73.

Table 3. Distant Metastasis (M)a

M0

No distant metastasis.

M1

Distant metastasis.

aReprinted with permission from AJCC: Anus. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 165-73.

Table 4. Anatomic Stage/Prognostic Groupsa

Stage

T

N

M

0

Tis

N0

M0

I

T1

N0

M0

II

T2

N0

M0

T3

N0

M0

IIIA

T1

N1

M0

T2

N1

M0

T3

N1

M0

T4

N0

M0

IIIB

T4

N1

M0

Any T

N2

M0

Any T

N3

M0

IV

Any T

Any N

M1

aReprinted with permission from AJCC: Anus. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 165-73.

References:

  1. Anus. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 167-169.

Treatment Option Overview

Abdominoperineal resection leading to permanent colostomy was previously thought to be required for all but small anal cancers occurring below the dentate line with approximately 70% of patients surviving 5 or more years in single institutions,[1] but such surgery is no longer the treatment of choice.[2][3]

Radiation therapy alone may lead to a 5-year survival rate in excess of 70%, but high doses (≥60 Gy) may yield necrosis or fibrosis.[4] Chemotherapy with fluorouracil (5-FU) and cisplatin concurrent with lower-dose radiation therapy as utilized in the RTOG-8314 trial, for example, has a 5-year survival rate in excess of 70% with low levels of acute and chronic morbidity, and few patients require surgery for dermal or sphincter toxic effects.[5][6][7][8][9][10] The optimal dose of radiation with concurrent chemotherapy to optimize local control and minimize sphincter toxic effects has been studied in the RTOG-9208 trial, for example, and appears to be in the 45 Gy to 60 Gy range.[11][12]

The Anal Cancer Trial (ACT-1) from the United Kingdom Co-ordinating Committee on Cancer Research demonstrated the superiority of chemoradiation with 5-FU and mitomycin C (MMC) over radiation alone with regard to local failure and deaths from anal cancer.[13][Level of evidence: 1iiB] Long-term follow-up of this study has revealed 25.3 fewer patients with locoregional relapse and 12.5 fewer anal cancer deaths per 100 patients treated with chemoradiation compared with 100 patients treated with radiation alone. A 9.1% increase in nonanal cancer deaths was seen in the first 5 years following chemoradiation, which was not seen after 10 years.[14]

The choice of chemotherapy during concurrent chemoradiation has been the subject of several trials. Analysis of an intergroup trial that compared radiation therapy plus 5-FU and MMC with radiation therapy plus 5-FU alone in patients with anal cancer demonstrated lower colostomy rates as well as higher colostomy-free and disease-free survival (DFS) with the addition of MMC.[15]

A U.S. intergroup, randomized, phase III trial (RTOG 9811 [NCT00003596]) examined whether MMC could be replaced by cisplatin in combination with 5-FU during concurrent chemoradiation.[16] In the cisplatin arm of this study, two cycles of induction 5-FU and cisplatin were given before concurrent chemoradiation with 5-FU and cisplatin. The MMC arm had improved local control and colostomy-free survival, but no improvement was found in DFS or overall survival (OS).[16] Long-term follow-up of the RTOG-9811 trial has been published and demonstrated superior 5-year DFS and OS.[17] One potential explanation for the inferiority of the cisplatin arm is delay in time to radiation, given the induction strategy employed in this study.

A strategy of maintenance chemotherapy with 5-FU and cisplatin after chemoradiation with 5-FU and MMC or 5-FU and cisplatin was evaluated in the ACT-II (NCT00025090) trial, and 3-year progression-free survival was not improved (74% with maintenance chemotherapy vs. 73% without maintenance chemotherapy).[18] Induction chemotherapy and dose intensification were examined in the UNICANCER ACCORD-03 (NCT00003652) trial, which did not demonstrate an advantage in colostomy-free survival with induction chemotherapy with 5-FU and cisplatin or with radiation-dose intensification.[19]

Standard salvage therapy for those patients with either gross or microscopic residual disease following chemoradiation therapy has been abdominoperineal resection. Alternately, patients may be treated with additional salvage chemoradiation therapy in the form of 5-FU, cisplatin, and a radiation boost to potentially avoid permanent colostomy.[15]

Because of the small number of cases, information that can only come from patient participation in well-designed clinical trials is needed to improve the management of anal cancer. Patients with stages II, III, and IV disease should be considered candidates for clinical trials. Information about ongoing clinical trials is available from the NCI Web site.

HIV and Anal Cancer

The tolerance of patients with human immunodeficiency virus and anal carcinoma to standard 5-FU and MMC chemoradiation is not well defined.[20][21] Patients with pretreatment CD4 counts of less than 200 cells/μl may have increased acute and late toxic effects;[22][23] chemoradiation doses may require modification in this subset of patients.

References:

  1. Boman BM, Moertel CG, O'Connell MJ, et al.: Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer 54 (1): 114-25, 1984.

  2. Stearns MW Jr, Quan SH: Epidermoid carcinoma of the anorectum. Surg Gynecol Obstet 131 (5): 953-7, 1970.

  3. Cummings BJ: The Role of Radiation Therapy With 5-Fluorouracil in Anal Cancer. Semin Radiat Oncol 7 (4): 306-312, 1997.

  4. Cantril ST, Green JP, Schall GL, et al.: Primary radiation therapy in the treatment of anal carcinoma. Int J Radiat Oncol Biol Phys 9 (9): 1271-8, 1983.

  5. Leichman L, Nigro N, Vaitkevicius VK, et al.: Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med 78 (2): 211-5, 1985.

  6. Sischy B: The use of radiation therapy combined with chemotherapy in the management of squamous cell carcinoma of the anus and marginally resectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 11 (9): 1587-93, 1985.

  7. Sischy B, Doggett RL, Krall JM, et al.: Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 81 (11): 850-6, 1989.

  8. Cummings BJ: Anal cancer. Int J Radiat Oncol Biol Phys 19 (5): 1309-15, 1990.

  9. Zucali R, Doci R, Bombelli L: Combined chemotherapy--radiotherapy of anal cancer. Int J Radiat Oncol Biol Phys 19 (5): 1221-3, 1990.

  10. Fuchshuber PR, Rodriguez-Bigas M, Weber T, et al.: Anal canal and perianal epidermoid cancers. J Am Coll Surg 185 (5): 494-505, 1997.

  11. Fung CY, Willett CG, Efird JT, et al.: Chemoradiotherapy for anal carcinoma: what is the optimal radiation dose? Radiat Oncol Investig 2 (3): 152-6, 1994.

  12. John M, Pajak T, Flam M, et al.: Dose Escalation in Chemoradiation for Anal Cancer: Preliminary Results of RTOG 92-08 Cancer J Sci Am 2 (4): 205-11, 1996.

  13. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 348 (9034): 1049-54, 1996.

  14. Northover J, Glynne-Jones R, Sebag-Montefiore D, et al.: Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the first randomised UKCCCR Anal Cancer Trial (ACT I). Br J Cancer 102 (7): 1123-8, 2010.

  15. Flam M, John M, Pajak TF, et al.: Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14 (9): 2527-39, 1996.

  16. Ajani JA, Winter KA, Gunderson LL, et al.: Fluorouracil, mitomycin, and radiotherapy vs fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal: a randomized controlled trial. JAMA 299 (16): 1914-21, 2008.

  17. Gunderson LL, Winter KA, Ajani JA, et al.: Long-term update of US GI intergroup RTOG 98-11 phase III trial for anal carcinoma: survival, relapse, and colostomy failure with concurrent chemoradiation involving fluorouracil/mitomycin versus fluorouracil/cisplatin. J Clin Oncol 30 (35): 4344-51, 2012.

  18. James RD, Glynne-Jones R, Meadows HM, et al.: Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2 × 2 factorial trial. Lancet Oncol 14 (6): 516-24, 2013.

  19. Peiffert D, Tournier-Rangeard L, Gérard JP, et al.: Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized UNICANCER ACCORD 03 trial. J Clin Oncol 30 (16): 1941-8, 2012.

  20. Holland JM, Swift PS: Tolerance of patients with human immunodeficiency virus and anal carcinoma to treatment with combined chemotherapy and radiation therapy. Radiology 193 (1): 251-4, 1994.

  21. Peddada AV, Smith DE, Rao AR, et al.: Chemotherapy and low-dose radiotherapy in the treatment of HIV-infected patients with carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 37 (5): 1101-5, 1997.

  22. Hoffman R, Welton ML, Klencke B, et al.: The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer. Int J Radiat Oncol Biol Phys 44 (1): 127-31, 1999.

  23. Place RJ, Gregorcyk SG, Huber PJ, et al.: Outcome analysis of HIV-positive patients with anal squamous cell carcinoma. Dis Colon Rectum 44 (4): 506-12, 2001.

Stage 0 Anal Cancer

Stage 0 anal cancer is carcinoma in situ. Rarely diagnosed, it is a very early cancer that has not spread below the limiting membrane of the first layer of anal tissue.

Standard treatment options:

Surgical resection is used for treatment of lesions of the perianal area not involving the anal sphincter (approach depends on the location of the lesion in the anal canal).

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 anal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Stage I Anal Cancer

Stage I anal cancer was formerly treated with abdominoperineal resection. Current sphincter-sparing therapies include wide local excision for small tumors of the perianal skin or anal margin, or definitive chemoradiation (fluorouracil and mitomycin C [MMC]) for cancers of the anal canal. Salvage chemoradiation therapy (fluorouracil and cisplatin plus a radiation boost) may avoid permanent colostomy in patients with residual tumor following initial nonoperative therapy.[1] Radical resection is reserved for patients with incomplete responses or recurrent disease. Continued surveillance with rectal examination every 3 months for the first 2 years and endoscopy with biopsy when indicated after completion of sphincter-preserving therapy is important.

Standard treatment options:

  1. Small tumors of the perianal skin or anal margin not involving the anal sphincter may be adequately treated with local resection.[2]
  2. As evidenced in RTOG-9208 and RTOG-8314 trials, for example, all other stage I cancers of the anal canal that involve the anal sphincter or are too large for complete local excision are treated with external-beam radiation therapy (EBRT) with or without chemotherapy.[1][3][4][5][6][7][8][9]

    Chemotherapy with fluorouracil and MMC combined with primary radiation therapy appears to be more effective than radiation therapy alone.[10] The optimal dose of radiation with concurrent chemotherapy has been evaluated, as seen in the RTOG-9208 trial, for example.[11][12]

    Selected tumors are also suitable for interstitial radiation therapy.[4]

  3. Radical resection is reserved for residual or recurrent cancer in the anal canal after nonoperative therapy.
  4. Alternately, salvage chemotherapy with fluorouracil and cisplatin combined with a radiation boost may avoid a permanent colostomy in selected patients with small amounts of residual tumor following initial nonoperative therapy.[1]
  5. Interstitial iridium-192 implantation after EBRT may convert some patients with residual disease into complete responders.[13]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I anal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Flam M, John M, Pajak TF, et al.: Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14 (9): 2527-39, 1996.

  2. Enker WE, Heilwell M, Janov AJ, et al.: Improved survival in epidermoid carcinoma of the anus in association with preoperative multidisciplinary therapy. Arch Surg 121 (12): 1386-90, 1986.

  3. Papillon J, Mayer M, Montbarbon JF, et al.: A new approach to the management of epidermoid carcinoma of the anal canal. Cancer 51 (10): 1830-7, 1983.

  4. Cummings B, Keane T, Thomas G, et al.: Results and toxicity of the treatment of anal canal carcinoma by radiation therapy or radiation therapy and chemotherapy. Cancer 54 (10): 2062-8, 1984.

  5. Leichman L, Nigro N, Vaitkevicius VK, et al.: Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med 78 (2): 211-5, 1985.

  6. James RD, Pointon RS, Martin S: Local radiotherapy in the management of squamous carcinoma of the anus. Br J Surg 72 (4): 282-5, 1985.

  7. Sischy B: The use of radiation therapy combined with chemotherapy in the management of squamous cell carcinoma of the anus and marginally resectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 11 (9): 1587-93, 1985.

  8. Sischy B, Doggett RL, Krall JM, et al.: Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 81 (11): 850-6, 1989.

  9. Mitchell SE, Mendenhall WM, Zlotecki RA, et al.: Squamous cell carcinoma of the anal canal. Int J Radiat Oncol Biol Phys 49 (4): 1007-13, 2001.

  10. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 348 (9034): 1049-54, 1996.

  11. Fung CY, Willett CG, Efird JT, et al.: Chemoradiotherapy for anal carcinoma: what is the optimal radiation dose? Radiat Oncol Investig 2 (3): 152-6, 1994.

  12. John M, Pajak T, Flam M, et al.: Dose Escalation in Chemoradiation for Anal Cancer: Preliminary Results of RTOG 92-08 Cancer J Sci Am 2 (4): 205-11, 1996.

  13. Sandhu AP, Symonds RP, Robertson AG, et al.: Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience. Int J Radiat Oncol Biol Phys 40 (3): 575-81, 1998.

Stage II Anal Cancer

Stage II anal cancer was formerly treated with abdominoperineal resection. Current sphincter-sparing therapies include wide local excision for small tumors of the perianal skin or anal margin, or definitive chemoradiation (fluorouracil and mitomycin C [MMC]) for cancers of the anal canal. Salvage chemotherapy (fluorouracil with cisplatin plus a radiation boost) may avoid permanent colostomy in patients with residual tumor following initial nonoperative therapy. Radical resection is reserved for patients with incomplete responses or recurrent disease. Therefore, continued surveillance with rectal examination every 3 months for the first 2 years and an endoscopy with biopsy when indicated after completion of sphincter-preserving therapy is important.

Standard treatment options:

  1. Small tumors of the perianal skin or anal margin not involving the anal sphincter may be adequately treated with local resection.[1]
  2. All other stage II cancers of the anal canal that involve the anal sphincter or are too large for complete local excision are treated with external-beam radiation therapy plus chemotherapy as was shown in the RTOG-8314 trial, for example.[2][3][4][5][6][7][8]

    Chemotherapy with fluorouracil and MMC combined with primary radiation therapy appears to be more effective than radiation therapy alone.[9] The optimal dose of radiation with concurrent chemotherapy was studied, as seen in the RTOG-9811 and RTOG-9208 trials, for example.[10][11]

    Selected tumors are also suitable for interstitial radiation therapy.[3][12]

  3. Radical resection is reserved for continued residual or recurrent cancer in the anal canal after nonoperative therapy.
  4. Alternately, salvage chemotherapy with fluorouracil and cisplatin combined with a radiation boost may avoid a permanent colostomy in selected patients with small amounts of residual tumor following initial nonoperative therapy.[8]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II anal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Enker WE, Heilwell M, Janov AJ, et al.: Improved survival in epidermoid carcinoma of the anus in association with preoperative multidisciplinary therapy. Arch Surg 121 (12): 1386-90, 1986.

  2. Papillon J, Mayer M, Montbarbon JF, et al.: A new approach to the management of epidermoid carcinoma of the anal canal. Cancer 51 (10): 1830-7, 1983.

  3. Cummings B, Keane T, Thomas G, et al.: Results and toxicity of the treatment of anal canal carcinoma by radiation therapy or radiation therapy and chemotherapy. Cancer 54 (10): 2062-8, 1984.

  4. Leichman L, Nigro N, Vaitkevicius VK, et al.: Cancer of the anal canal. Model for preoperative adjuvant combined modality therapy. Am J Med 78 (2): 211-5, 1985.

  5. James RD, Pointon RS, Martin S: Local radiotherapy in the management of squamous carcinoma of the anus. Br J Surg 72 (4): 282-5, 1985.

  6. Sischy B: The use of radiation therapy combined with chemotherapy in the management of squamous cell carcinoma of the anus and marginally resectable adenocarcinoma of the rectum. Int J Radiat Oncol Biol Phys 11 (9): 1587-93, 1985.

  7. Sischy B, Doggett RL, Krall JM, et al.: Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 81 (11): 850-6, 1989.

  8. Flam M, John M, Pajak TF, et al.: Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14 (9): 2527-39, 1996.

  9. Epidermoid anal cancer: results from the UKCCCR randomised trial of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin. UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee on Cancer Research. Lancet 348 (9034): 1049-54, 1996.

  10. Fung CY, Willett CG, Efird JT, et al.: Chemoradiotherapy for anal carcinoma: what is the optimal radiation dose? Radiat Oncol Investig 2 (3): 152-6, 1994.

  11. John M, Pajak T, Flam M, et al.: Dose Escalation in Chemoradiation for Anal Cancer: Preliminary Results of RTOG 92-08 Cancer J Sci Am 2 (4): 205-11, 1996.

  12. Sandhu AP, Symonds RP, Robertson AG, et al.: Interstitial iridium-192 implantation combined with external radiotherapy in anal cancer: ten years experience. Int J Radiat Oncol Biol Phys 40 (3): 575-81, 1998.

Stage IIIA Anal Cancer

Stage IIIA anal cancer presents clinically as stage II in most instances and is determined to be IIIA by clinically evident perirectal nodal disease or adjacent organ involvement. Endorectal or endoanal ultrasound may aid in pretreatment staging.

Standard treatment options:

  1. As shown in the RTOG-8314 trial, treatment used is the same as for stage I and II disease, including the use of radiation therapy plus chemotherapy.[1][2]
  2. Radical resection is reserved for continued residual or recurrent cancer in the anal canal after nonoperative therapy.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIIA anal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Sischy B, Doggett RL, Krall JM, et al.: Definitive irradiation and chemotherapy for radiosensitization in management of anal carcinoma: interim report on Radiation Therapy Oncology Group study no. 8314. J Natl Cancer Inst 81 (11): 850-6, 1989.

  2. Flam M, John M, Pajak TF, et al.: Role of mitomycin in combination with fluorouracil and radiotherapy, and of salvage chemoradiation in the definitive nonsurgical treatment of epidermoid carcinoma of the anal canal: results of a phase III randomized intergroup study. J Clin Oncol 14 (9): 2527-39, 1996.

Stage IIIB Anal Cancer

The presence of inguinal nodes that are involved with metastatic disease (unilateral or bilateral) is a poor prognostic sign, though cure of this stage of disease is possible. Because of the poor prognosis associated with this stage, patients should be included in clinical trials whenever possible.

Standard treatment options:

  • Radiation therapy plus chemotherapy (as described for stage II) with surgical resection of residual disease at the primary site (local resection or abdominoperineal resection) and unilateral or bilateral superficial and deep inguinal node dissection for residual or recurrent tumor.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIIB anal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Stage IV Anal Cancer

There is no standard chemotherapy for patients with metastatic disease. Palliation of symptoms from the primary lesion is of major importance. Patients in this stage should be considered candidates for clinical trials.

Standard treatment options:

  1. Palliative surgery.
  2. Palliative radiation therapy.
  3. Palliative combined chemotherapy and radiation therapy.
  4. Clinical trials.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IV anal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

Recurrent Anal Cancer

Local recurrences and persistent disease after treatment with radiation therapy and chemotherapy or surgery as the primary treatment may be controlled by using the alternate treatment (surgical resection after radiation and vice versa).[1] Clinical trials are exploring the use of radiation therapy with chemotherapy and radiosensitizers to improve local control.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent anal cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Longo WE, Vernava AM 3rd, Wade TP, et al.: Recurrent squamous cell carcinoma of the anal canal. Predictors of initial treatment failure and results of salvage therapy. Ann Surg 220 (1): 40-9, 1994.


This information is provided by the National Cancer Institute.

This information was last updated on July 31, 2014.

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