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Home > Patient & Family Resources > Health Library > Anal Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI]
This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.
Incidence and Mortality
Estimated new cases and deaths from anal, anal canal, and anorectal cancer in the United States in 2018.
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 website.
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]
Other PDQ summaries containing information related to anal cancer include the following:
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. Adenocarcinomas from anal glands or fistulae formation and melanomas are rare. Treatment of anal melanoma is not included in this summary.
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. Tumors of the anal margin (below the anal verge and involving the perianal hair-bearing skin) are classified with skin tumors.
AJCC Stage Groupings and TNM Definitions
The following is a staging system for anal canal cancer that has been described by the AJCC and the International Union Against Cancer.
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, 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. 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.[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.
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.
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. 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). Long-term follow-up of the RTOG-9811 trial has been published and demonstrated superior 5-year DFS and OS. 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). 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.
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.
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 website.
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.
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
Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.
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. 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.
Chemotherapy with fluorouracil and MMC combined with primary radiation therapy appears to be more effective than radiation therapy alone. 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.
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.
Chemotherapy with fluorouracil and MMC combined with primary radiation therapy appears to be more effective than radiation therapy alone. The optimal dose of radiation with concurrent chemotherapy was studied, as seen in the RTOG-9811 (NCT00003596) and RTOG-9208 trials, for example.[10,11]
Selected tumors are also suitable for interstitial radiation therapy.[3,12]
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.
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.
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.
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). Clinical trials are exploring the use of radiation therapy with chemotherapy and radiosensitizers to improve local control.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Anal Cancer
Updated statistics with estimated new cases and deaths for 2018 (cited American Cancer Society as reference 1).
Stage Information for Anal Cancer
Updated staging information for 2017 (cited American Joint Committee on Cancer as reference 1).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of anal cancer. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Anal Cancer Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
Permission to Use This Summary
PDQ is a registered trademark. Although the content of PDQ documents can be used freely as text, it cannot be identified as an NCI PDQ cancer information summary unless it is presented in its entirety and is regularly updated. However, an author would be permitted to write a sentence such as "NCI's PDQ cancer information summary about breast cancer prevention states the risks succinctly: [include excerpt from the summary]."
The preferred citation for this PDQ summary is:
PDQ® Adult Treatment Editorial Board. PDQ Anal Cancer Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/anal/hp/anal-treatment-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389221]
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Managing Cancer Care page.
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Last Revised: 2018-02-01
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