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  • Anal Cancer Treatment (PDQ®): Treatment – Health Professional Information [NCI]

Anal Cancer Treatment (PDQ®): Treatment – Health Professional Information [NCI]

Incidence and Mortality Estimated new cases and deaths from anal, anal canal, and anorectal cancer in the United States in 2019:[ 1] New cases: 8,300. Deaths: 1,280. Prognosis and Survival Anal cancer is usually curable. The three major prognostic factors are site (anal canal vs. perianal skin), size (primary tumors…

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.

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 2019:[1]

  • New cases: 8,300.
  • Deaths: 1,280.

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.

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]

Related Summaries

Other PDQ summaries containing information related to anal cancer include the following:

  • Anal Cancer Prevention

References:

  1. American Cancer Society: Cancer Facts and Figures 2019. Atlanta, Ga: American Cancer Society, 2019. Available online. Last accessed January 23, 2019.
  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.

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.[1] The AJCC has designated staging by TNM (tumor, node, metastasis) classification to define anal cancer.

Table 1. Definitions of TNM Stage 0a
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
0 Tis, N0, M0 Tis = High-grade squamous intraepithelial lesion (previously termed carcinomain situ[e.g., Bowen disease, anal intraepithelial neoplasia II–III, high-grade anal intraepithelial neoplasia]).
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 2. Definitions of TNM Stage Ia
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
I T1, N0, M0 T1 = Tumor ≤2 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 3. Definitions of TNM Stage IIAa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
IIA T2, N0, M0 T2 = Tumor >2 cm but ≤5 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 4. Definitions of TNM Stage IIBa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
IIB T3, N0, M0 T3 = Tumor >5 cm.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 5. Definitions of TNM Stage IIIAa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
IIIA T1, N1, M0 T1 = Tumor ≤2 cm.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
T2, N1, M0 T2 = Tumor >2 cm but ≤5 cm.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
Table 6. Definitions of TNM Stage IIIBa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
IIIB T4, N0, M0 T4 = Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder.
N0 = No regional lymph node metastasis.
M0 = No distant metastasis.
Table 7. Definitions of TNM Stage IIICa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
IIIC T3, N1, M0 T3 = Tumor >5 cm.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
T4, N1, M0 T4 = Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
M0 = No distant metastasis.
Table 8. Definitions of Stage IVa
Stage TNM Description
T = primary tumor; N = regional lymph node; M = distant metastasis.
a Reprinted with permission from AJCC: Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.:AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp 275–84.
IV Any T, Any N, M1 TX = Primary tumor not assessed.
T0 = No evidence of primary tumor.
Tis = High-grade squamous intraepithelial lesion (previously termed carcinomain situ. Bowen disease, anal intraepithelial neoplasia II–III, high-grade anal intraepithelial neoplasia).
T1 = Tumor ≤2 cm.
T2 = Tumor >2 cm but ≤5 cm.
T3 = Tumor >5 cm.
T4 = Tumor of any size invading adjacent organ(s), such as the vagina, urethra, or bladder.
NX = Regional lymph nodes cannot be assessed.
N0 = No regional lymph node metastasis.
N1 = Metastasis in inguinal, mesorectal, internal iliac, or external iliac nodes.
–N1a = Metastasis in inguinal, mesorectal, or internal iliac lymph nodes.
–N1b = Metastasis in external iliac lymph nodes.
–N1c = Metastasis in external iliac with any N1a nodes.
M1 = Distant metastasis.

References:

  1. Anus. In: Amin MB, Edge SB, Greene FL, et al., eds.: AJCC Cancer Staging Manual. 8th ed. New York, NY: Springer, 2017, pp. 275–84.

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 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.

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 Treatment

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 Treatment

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 Ir 192 implantation after EBRT may convert some patients with residual disease into complete responders.[13]

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.

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 Treatment

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 (NCT00003596) 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

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.

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 Treatment

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

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.

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 Treatment

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

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 IV Anal Cancer Treatment

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

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.

Recurrent Anal Cancer Treatment

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

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.

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.

Changes to This Summary (01 / 29 / 2019)

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 2019 (cited American Cancer Society 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.

About This PDQ Summary

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 reviewer for Anal Cancer Treatment is:

  • Valerie Lee, MD (Johns Hopkins University)

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.

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 Managing Cancer Care page.

Contact Us

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

Last Revised: 2019-01-29

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