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NCI/PDQ^® Health professionals: Anal Cancer Treatment (PDQ®)

National Cancer Institute
Last Modified: July 12, 2012

TABLE OF CONTENTS

• General Information About Anal Cancer
  • Incidence and Mortality

• Cellular Classification of Anal Cancer

• Stage Information for Anal Cancer
  • Definitions of TNM

• Treatment Option Overview
  • HIV and Anal Cancer

• Stage 0 Anal Cancer
  • Current Clinical Trials

• Stage I Anal Cancer
  • Current Clinical Trials

• Stage II Anal Cancer
  • Current Clinical Trials

• Stage IIIA Anal Cancer
  • Current Clinical Trials

• Stage IIIB Anal Cancer
  • Current Clinical Trials

• Stage IV Anal Cancer
  • Current Clinical Trials

• Recurrent Anal Cancer
  • Current Clinical Trials

• Changes to This Summary (04/20/2012)

• About This PDQ® Summary
  • Purpose of This Summary
  • Reviewers and Updates
  • Levels of Evidence
  • Permission to Use This Summary
  • Disclaimer
  • Contact Us

• Get More Information From NCI

General Information About Anal Cancer

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Incidence and Mortality

Estimated new cases and deaths from anal, anal canal, and anorectal cancer in the United States in 2012: 1

• New cases: 6,230.
• Deaths: 780.

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.

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 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 2012. Atlanta, Ga: American Cancer Society, 2012. Available online [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
7. Ryan DP, Compton CC, Mayer RJ: Carcinoma of the anal canal. N Engl J Med 342 (11): 792-800, 2000. [PUBMED Abstract]

Cellular Classification of Anal Cancer

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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. [PUBMED Abstract]

Stage Information for Anal Cancer

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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. 1. Primary Tumor (T)^a

^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.

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 IIIII.)
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

Table 2. 2. Regional Lymph Nodes (N)^a

^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.

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.

Table 3. 3. Distant Metastasis (M)^a

^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.

M0	No distant metastasis.
M1	Distant metastasis.

Table 4. 4. Anatomic Stage/Prognostic Groups^a

^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.

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

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. [PUBMED Abstract]

Treatment Option Overview

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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%, though high doses (60 Gy) may yield necrosis or fibrosis. 4 Chemotherapy concurrent with lower-dose radiation therapy as evidenced 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 Analysis of an intergroup trial that compared radiation therapy plus fluorouracil/mitomycin with radiation therapy plus fluorouracil alone in patients with anal cancer has shown improved results (lower colostomy rates and higher colostomy-free and disease-free survival) with the addition of mitomycin. 13 Radiation with continuous infusion of fluorouracil plus cisplatin has been evaluated, as seen in the RTOG-9811 trial. 14 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 fluorouracil, cisplatin, and a radiation boost to potentially avoid permanent colostomy. 13

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 (HIV) and anal carcinoma to standard fluorouracil/mitomycin chemoradiation is not well defined. 15 16 Patients with pretreatment CD4 counts of less than 200 cells/¼l may have increased acute and late toxic effects; 17 18 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. [PUBMED Abstract]
2. Stearns MW Jr, Quan SH: Epidermoid carcinoma of the anorectum. Surg Gynecol Obstet 131 (5): 953-7, 1970. [PUBMED Abstract]
3. Cummings BJ: The Role of Radiation Therapy With 5-Fluorouracil in Anal Cancer. Semin Radiat Oncol 7 (4): 306-312, 1997. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
8. Cummings BJ: Anal cancer. Int J Radiat Oncol Biol Phys 19 (5): 1309-15, 1990. [PUBMED Abstract]
9. Zucali R, Doci R, Bombelli L: Combined chemotherapy--radiotherapy of anal cancer. Int J Radiat Oncol Biol Phys 19 (5): 1221-3, 1990. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
13. 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. [PUBMED Abstract]
14. Rich TA, Ajani JA, Morrison WH, et al.: Chemoradiation therapy for anal cancer: radiation plus continuous infusion of 5-fluorouracil with or without cisplatin. Radiother Oncol 27 (3): 209-15, 1993. [PUBMED Abstract]
15. 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. [PUBMED Abstract]
16. 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. [PUBMED Abstract]
17. 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. [PUBMED Abstract]
18. 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. [PUBMED Abstract]

Stage 0 Anal Cancer

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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

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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) 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/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 mitomycin combined with primary radiation therapy appears to be more effective than radiation therapy alone. 10 The The optimal dose of radiation with concurrent chemotherapy has been evaluated, as seen in the optimal dose of radiation with concurrent chemotherapy has been evaluated, as seen in the RTOG-9208RTOG-9208 trial, for example. 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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]

Stage II Anal Cancer

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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) 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 endoscopy/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 mitomycin combined with primary radiation therapy appears to be more effective than radiation therapy alone. 9 The The optimal dose of radiation with concurrent chemotherapy was studied, as seen in the optimal dose of radiation with concurrent chemotherapy was studied, as seen in the RTOG-9811RTOG-9811 and and RTOG-9208RTOG-9208 trials, for example. 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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]
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. [PUBMED Abstract]

Stage IIIA Anal Cancer

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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. [PUBMED Abstract]
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. [PUBMED Abstract]

Stage IIIB Anal Cancer

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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

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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

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Local recurrences and/or 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/or 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. [PUBMED Abstract]

Changes to This Summary (04/20/2012)

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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.

Editorial changes were made to this summary.

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.

About This PDQ® Summary

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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:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

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:

• David P. Ryan, MD (Massachusetts General Hospital)
• Jennifer Wo, MD (Massachusetts General Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. 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:

National Cancer Institute: PDQ® Anal Cancer Treatment. Bethesda, MD: National Cancer Institute. Date last modified . Available at: http://cancer.gov/cancertopics/pdq/treatment/anal/HealthProfessional. Accessed .

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.

Disclaimer

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 Coping with Cancer: Financial, Insurance, and Legal Information page.

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More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site's Contact Form.

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Call 1-800-4-CANCER

For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.

Chat online

The NCI's LiveHelp online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.

Write to us

For more information from the NCI, please write to this address:

• NCI Public Inquiries Office
• Suite 3036A
• 6116 Executive Boulevard, MSC8322
• Bethesda, MD 20892-8322

Search the NCI Web site

The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.

There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.

Find Publications

The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).