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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 2019:
Prognosis and Survival
The two major prognostic factors for anal cancer are tumor size (primary tumors <2 cm in size have a better prognosis) and nodal status (refer to the American Joint Committee on Cancer Stage Groupings and TNM Definitions section of this summary for more information). Nodal drainage of the anus follows the inguinal vein. The initial evaluation of a patient with anal cancer will include a careful clinical examination of the inguinal region and biopsy of any palpable lymph nodes.
Anal cancer is usually curable. At presentation, most patients have T1 or T2 disease (≤5 cm), and fewer than 20% of patients have node-positive disease. The 5-year survival for these early-stage patients exceeds 85%.[3,4] Even in patients with node-positive disease, 5-year survival exceeds 50% in the absence of invasion into adjacent organs or distant metastases.
Overall, the risk of anal cancer is rising due to increased incidence of human papilloma virus (HPV) infection.[6,7] Ninety-five percent of anal cancers are HPV related, with the highest risk for serotypes 16 and 18. Involvement of HPV can be pathologically correlated with P16+ staining. Patients with HIV have a higher risk of HPV coinfection, and consequently have a higher risk of anal cancer.
Data suggest that certain sexual practices, such as receptive anal intercourse or a high lifetime number of sexual partners, portend an increased risk of anal cancer. These practices may have led to an increase in the number of individuals at risk of infection with HPV.
Another PDQ summary containing information related to anal cancer is the following:
Squamous cell (epidermoid) carcinomas make up the majority of all primary cancers of the anus. Historically, a subset of tumors arising from the epithelial transitional zone were categorized as cloacogenic or basaloid tumors; however, these tumors are now recognized as nonkeratinizing squamous cell cancers and are similarly associated with human papilloma virus.[1,2]
Lesions in the hair-bearing skin distal to the squamous mucocutaneous junction are defined as perianal cancers. These are typically treated the same as anal canal cancers, although local therapy alone can be considered for discrete skin lesions with significant separation from the anal verge.
Adenocarcinomas starting in anal glands or fistulae formation are rare and generally have clinical features that are similar to rectal adenocarcinoma. (Refer to the Clinical Features section in the PDQ summary on Rectal Cancer Treatment for more information.)
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. Tumors of the anal margin (below the anal verge and involving the perianal hair-bearing skin) are classified with skin tumors.
American Joint Committee on Cancer (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. The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define anal cancer.
Standard treatment options for anal cancer are described in Table 6.
The optimal approach in patients with advanced disease in still under clinical evaluation. Information about ongoing clinical trials is available from the NCI website.
Standard Treatment Options for 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 to treat lesions of the perianal area not involving the anal sphincter. The surgical 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.
Standard Treatment Options for Stages I, II, and III Anal Cancer
Current sphincter-sparing therapies include wide local excision for small tumors of the perianal skin or anal margin, or definitive chemoradiation therapy (fluorouracil and mitomycin C [MMC]) for cancers of the anal canal. 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 to monitor for recurrence.
Because of historically high rates of recurrence with colostomy alone, chemoradiation therapy is the preferred approach for patients with anal cancer in the absence of distant metastases.
Evidence (chemoradiation therapy):
In this trial, 585 patients were prospectively randomly assigned to receive 45 Gy of radiation in 20 or 25 fractions with or without 5-FU by continuous infusion (750 mg/m2 for 5 days or 1,000 mg/m2 for 4 days) in the first and final weeks of radiation, plus a single dose of MMC (12 mg/m2) on the first day.
Subsequent trials have found capecitabine to be a reasonable replacement for 5-FU in combination with MMC and radiation therapy.[4,5]
While the ACT I and EORTC randomized trials established chemoradiation therapy as the preferred approach for nonmetastatic anal cancer, the substantial hematologic, renal, and pulmonary toxicity of MMC has prompted studies of alternative regimens.
Evidence (chemoradiation therapy [alternative regimens]):
Two large intergroup trials studied the substitution of cisplatin for MMC, with differing conclusions.
The best time to assess a complete clinical response after chemoradiation therapy is generally after 26 weeks because delayed responses are seen. Residual disease or subsequent local recurrence require further treatment.
The standard salvage therapy for patients with either gross or microscopic residual disease after chemoradiation therapy has been abdominoperineal resection. Alternatively, patients may be treated with additional salvage chemoradiation therapy, chemotherapy alone, or immunotherapy.[11,12]
The optimal radiation dose in various situations has not been determined. There is insufficient evidence to determine whether the dose should be escalated for patients with T3 to T4 disease or nodal metastases, or potentially de-escalated for patients with early-stage tumors smaller than 1 cm. It is also unclear whether the chemotherapy backbone can be safely omitted for some patients with early-stage tumors, and whether such a strategy would affect the optimal dose of radiation. The roles for newer strategies such as intensity-modulated radiation therapy, proton beam therapy, and brachytherapy have yet to be conclusively determined.[13,14,15] Based on the National Cancer Database, higher volume radiation oncology centers report improved OS for anal cancer patients.
Standard Treatment Options for Stage IV Anal Cancer
These promising findings have led international investigators to use carboplatin and paclitaxel as a new backbone in trials for advanced-stage disease, as well as a potential partner for use with radiation therapy. Other chemotherapy regimens, such as modified docetaxel, cisplatin, and 5-FU, are currently under clinical evaluation.
Although there is no clear standard of care for patients with metastatic disease, recent studies are uncovering promising new avenues for systemic treatment. Palliation of symptoms from the primary lesion is of major importance. Patients in this stage should be strongly considered for clinical trials.
The tolerance of patients with HIV and anal carcinoma to standard fluorouracil and mitomycin C (MMC) chemoradiation therapy is not well defined.[1,2] In general, patients with HIV are treated similarly to other patients and have similar outcomes, particularly in the era of highly active antiretroviral therapy (HAART). Patients with pretreatment CD4 counts of fewer than 200 cells/μl may have increased acute and late toxic effects.[3,4] Therefore, patients with a history of AIDS-related complications may have difficulty tolerating a standard regimen, necessitating a dose adjustment or omission of MMC.
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). Salvage chemoradiation therapy with fluorouracil and cisplatin plus a radiation boost may avoid permanent colostomy in patients with residual tumor after initial nonoperative therapy. Clinical trials are exploring the use of radiation therapy with chemotherapy and radiosensitizers to improve local control.
Preliminary studies in stage IV disease suggest the potential for benefit from alternative chemotherapy regimens (such as carboplatin and paclitaxel in the InterACCT [NCT02560298] trial) or immune checkpoint inhibitors (as in NCI9673 [NCT02314169] and KEYNOTE-028 [NCT02054806]) in this setting.
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.
This summary was comprehensively reviewed and extensively revised.
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 reviewer for Anal Cancer Treatment is:
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: 2019-08-16
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