Overview An estimated 5290 new cases (2100 men and 3190 women) of anal cancer (involving the anus, anal canal, or anorectum) will occur in the United States in 2009, accounting for approximately 1.9% of digestive system cancers, and an estimated 710 deaths due to anal cancer. Although considered to be a rare type of cancer, the incidence rate of invasive anal carcinoma in the United States increased by approximately 1.6-fold for men and 1.5-fold for women from 1973-1979 to 1994-2000 (see Risk Factors, facing page). This manuscript summarizes the NCCN Clinical Practice Guidelines in Oncology for managing squamous cell anal carcinoma, which represents the most common histologic form of the disease. Other types of cancers occurring in the anal region are addressed in other NCCN guidelines (i.e., anal adenocarcinoma and anal melanoma are managed according to the NCCN Clinical Practice Guidelines in Oncology on Rectal Cancer and Melanoma, respectively). Except where noted, the recommendations in these guidelines are classified as category 2A, meaning that uniform NCCN consensus was present among the panel based on lower-level evidence that the recommendation is appropriate. The panel unanimously endorses patient participation in a clinical trial over standard or accepted therapy. Risk Factors Anal carcinoma has been associated with human papilloma virus (HPV) infection (anal-genital warts); history of receptive anal intercourse or sexually transmitted disease; history of cervical, vulvar, or vaginal cancer; immunosuppression after solid organ transplantation or HIV infection; and smoking. Currently, the association between anal carcinoma and persistent infection with a high-risk form...
  • 1.

    JemalASiegelRWardE. Cancer statistics, 2009. CA Cancer J Clin2009;59:225229.

  • 2.

    JohnsonLGMadeleineMMNewcomerLM. Anal cancer incidence and survival: the surveillance, epidemiology, and end results experience, 1973-2000. Cancer2004;101:281288.

    • Search Google Scholar
    • Export Citation
  • 3.

    RyanDPComptonCCMayerRJ. Carcinoma of the anal canal. N Engl J Med2000;342:792800.

  • 4.

    FrischMGlimeliusBvan den BruleAJ. Sexually transmitted infection as a cause of anal cancer. N Engl J Med1997;337:13501358.

  • 5.

    DalingJRMadeleineMMGodefroy JohnsonL. Human papillomavirus, smoking, and sexual practices in the etiology of anal cancer. Cancer2004;101;270280.

    • Search Google Scholar
    • Export Citation
  • 6.

    De VurstHCliffordGMNascimentoMC. Prevalence and type distribution of human papillomavirus in carcinoma and intraepithelial neoplasia of the vulva, vagina and anus: a meta-analysis. Int J Cancer2009;124:16261636.

    • Search Google Scholar
    • Export Citation
  • 7.

    HootsBEPalefskyJMPimentaJMSmithJS. Human papillomavirus type distribution in anal cancer and anal intraepithelial lesions. Int J Cancer2009;124:23752383.

    • Search Google Scholar
    • Export Citation
  • 8.

    GervazPAllalASVilligerP. Squamous cell carcinoma of the anus: another sexually transmitted disease. Swiss Med Wkly2003;133:353359.

  • 9.

    DezubeBJ. HIV-associated anal squamous cell cancer: an otherwise preventable disease. J Clin Oncol2006;24:45164517.

  • 10.

    PatelPHansonDLSullivanPS. Incidence of types of cancer among HIV-infected persons compared with the general population in the United States, 1992–2003. Ann Intern Med2008;148:728736.

    • Search Google Scholar
    • Export Citation
  • 11.

    CummingsBJAjaniJASwallowCJ. Cancer of the anal region. In: DeVita VT Lawrence TS Rosenberg SA eds.Cancer: Principles and Practice of Oncology 8th ed.Philadelphia: Lippincott, Williams & Wilkins; 2008.

    • Search Google Scholar
    • Export Citation
  • 12.

    NivatvongsSSternHSFrydDS. The length of the anal canal. Dis Colon Rectum1981;24:600601.

  • 13.

    RickertRRComptonCC. Protocol for the examination of specimens from patients with carcinomas of the anus and anal canal: a basis for checklists. Cancer Committee of the College of American Pathologists. Arch Pathol Lab Med2000;124:2125.

    • Search Google Scholar
    • Export Citation
  • 14.

    GreeneFPageDFlemingIFritzA. AJCC Cancer Staging Manual. New York: Springer-Verlag; 2002.

  • 15.

    FengerCFritschMMartiMCParcR. Tumours of the anal canal. In: Hamilton SR Aaltonen LA eds.World Health Organisation Classification of Tumours. Pathology and Genetics of Tumours of the Digestive System. IARC Press: Lyon; 2000;145155.

    • Search Google Scholar
    • Export Citation
  • 16.

    JassJRSobinLH. Histological typing of intestinal tumours. Heidelberg: Springer-Verlag; 1989.

  • 17.

    FengerC. Prognostic factors in anal carcinoma. Pathology2002;34:53578.

  • 18.

    CummingsBJ. Current management of anal canal cancer. Semin Oncol2005;32(Suppl 9):S123128.

  • 19.

    GerardJPChapetOSamieiF. Management of inguinal lymph node metastases in patients with carcinoma of the anal canal: experience in a series of 270 patients treated in Lyon and review of the literature. Cancer2001;92:7784.

    • Search Google Scholar
    • Export Citation
  • 20.

    BomanBMMoertelCGO'ConnellMJ. Carcinoma of the anal canal. A clinical and pathologic study of 188 cases. Cancer1984;54:114125.

  • 21.

    BilimoriaKYBentremDJRockCE. Outcomes and prognostic factors for squamous-cell carcinoma of the anal cancer: analysis of patients from the National Cancer Data Base. Dis Colon Rectum2009;52:624631.

    • Search Google Scholar
    • Export Citation
  • 22.

    FuchshuberPRRodriguez-BigasMWeberTPetrelliNJ. Anal canal and perianal epidermoid cancers. J Am Coll Surg1997;185:494505.

  • 23.

    FrostDBRichardsPCMontagueED. Epidermoid cancer of the anorectum. Cancer1984;53:1285.

  • 24.

    WadeDSHerreraLCastilloNBPetrelliNJ. Metastases to the lymph nodes in epidermoid carcinoma of the anal canal studied by a clearing technique. Surg Gynecol Obstet1989;169:238242.

    • Search Google Scholar
    • Export Citation
  • 25.

    CotterSEGrigsbyPWSiegelBA. FDG-PET/CT in the evaluation of anal carcinoma. Int J Radiat Oncol Biol Phys2006;65:720725.

  • 26.

    TrautmannTGZugerJH. Positron emission tomography for pretreatment staging and posttreatment evaluation in cancer of the anal canal. Mol Imaging Biol2005;7:309313.

    • Search Google Scholar
    • Export Citation
  • 27.

    PepekJMWilletCGCzitoBG. Radiation therapy advances for treatment of anal cancer. J Natl Compr Canc Netw2010;8:123129.

  • 28.

    FrischMGoodmanMT. Human papillomavirus-associated carcinomas in Hawaii and the mainland U.S.Cancer2000;88:14641469.

  • 29.

    NigroNDVaitkeviciusVKConsidineBJr. Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum1974;17:354356.

    • Search Google Scholar
    • Export Citation
  • 30.

    CummingsBJKeaneTJO'SullivanB. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys1991;21:11151125.

    • Search Google Scholar
    • Export Citation
  • 31.

    PapillonJChassardJL. Respective roles of radiotherapy and surgery in the management of epidermoid carcinoma of the anal margin. Series of 57 patients. Dis Colon Rectum1992;35:422429.

    • Search Google Scholar
    • Export Citation
  • 32.

    UronisHEBendellJC. Anal cancer: an overview. Oncologist2007;12:524534.

  • 33.

    BartelinkHRoelofsenFEschwegeF. Concomitant radiotherapy and chemotherapy is superior to radiotherapy alone in the treatment of locally advanced anal cancer: results of a phase III randomized trial of the European Organization for Research and Treatment of Cancer Radiotherapy and Gastrointestinal Cooperative groups. J Clin Oncol1997;15:20402049.

    • Search Google Scholar
    • Export Citation
  • 34.

    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 Coordinating Committee on Cancer Research. Lancet1996;348:10491054.

    • Search Google Scholar
    • Export Citation
  • 35.

    FlamMJohnMPajakTF. 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 Oncol1996;14:25272539.

    • Search Google Scholar
    • Export Citation
  • 36.

    CrehangeGBossetMLorchelF. Combining cisplatin and mitomycin with radiotherapy in anal carcinoma. Dis Colon Rectum2006;50:4349.

  • 37.

    AjaniJAWinterKAGundersonLL. Fluorouracil, mitomycin, and radiotherapy vs. fluorouracil, cisplatin, and radiotherapy for carcinoma of the anal canal. A randomized controlled trial. JAMA2008;299:19141921.

    • Search Google Scholar
    • Export Citation
  • 38.

    EngCCraneCHRodriguez-BigasMA. Should cisplatin be avoided in the treatment of locally advanced squamous cell carcinoma of the anal canal?Nature Clinical Practice Gastroenterology & Hepatology2009;6:1617.

    • Search Google Scholar
    • Export Citation
  • 39.

    CzitoBGWillettCG. Current management of anal canal cancer. Gastrointestinal Cancers. Curr Oncol Rep2009;11:186192.

  • 40.

    AjaniJAWinterKAGundersonLL. US Intergroup Anal Carcinoma Trial: tumor diameter predicts for colostomy. J Clin Oncol2009;27:11161121.

    • Search Google Scholar
    • Export Citation
  • 41.

    JamesRWanSGlynne-JonesD. A randomised trial of chemoradiation using mitomycin or cisplatin with or without maintenance cisplatin/5-FU in squamous cell carcinoma of the anus. ACT II [abstract]. J Clin Oncol2009;27(Suppl 1):Abstract LBA4009.

    • Search Google Scholar
    • Export Citation
  • 42.

    OrtholanCRamaioliAPeiffertD. Anal canal carcinoma: early-stage tumors < or =10 mm (T1 or Tis): therapeutic options and original pattern of local failure after radiotherapy. Int J Radiat Oncol Biol Phys2005;62:479485.

    • Search Google Scholar
    • Export Citation
  • 43.

    FerrignoRNakamuraRADos Santos NovaesPE. Radiochemotherapy in the conservative treatment of anal canal carcinoma: retrospective analysis of results and radiation dose effectiveness. Int J Radiat Oncol Biol Phys2005;61:11361142.

    • Search Google Scholar
    • Export Citation
  • 44.

    HuangKHaas-KoganDWeinbergVKriegR. Higher radiation dose with a shorter treatment duration improves outcome for locally advanced carcinoma of anal canal. World J Gastroenterol2007;13:895900.

    • Search Google Scholar
    • Export Citation
  • 45.

    KonskiAGarciaMJrJohnM. Evaluation of planned treatment breaks during radiation therapy for anal cancer: update of RTOG 92-08. Int J Radiat Oncol Biol Phys2008;72:114118.

    • Search Google Scholar
    • Export Citation
  • 46.

    GrafRWustPHildebrandtB. Impact of overall treatment time on local control of anal cancer treated with radiochemotherapy. Oncology2003;65:1422.

    • Search Google Scholar
    • Export Citation
  • 47.

    RoohipourRPatilSGoodmanKA. Squamous-cell carcinoma of the anal canal: predictors of treatment outcome. Dis Colon Rectum2008;51:147153.

    • Search Google Scholar
    • Export Citation
  • 48.

    de BreeEvan RuthSDewitLGZoetmulderFA. High risk of colostomy with primary radiotherapy for anal cancer. Ann Surg Oncol2007;14:100108.

    • Search Google Scholar
    • Export Citation
  • 49.

    BaxterNNHabermannEBTepperJE. Risk of pelvic fracture in older women following pelvic irradiation. JAMA2005;294:25872593.

  • 50.

    LinABen-JosefE. Intensity-modulated radiation therapy for the treatment of anal cancer. Clin Colorectal Cancer2007;6:716719.

  • 51.

    SalamaJKMellLKSchomasDA. Concurrent chemotherapy and intensity-modulated radiation therapy for anal canal cancer patients: a multicenter experience. J Clin Oncol2007;25:45814586.

    • Search Google Scholar
    • Export Citation
  • 52.

    MilanoMTJaniABFarreyKJ. Intensity-modulated radiation therapy (IMRT) in the treatment of anal cancer: toxicity and clinical outcome. Int J Radiat Oncol Biol Phys2005;63:354361.

    • Search Google Scholar
    • Export Citation
  • 53.

    ChenYJLiuATsaiPT. Organ sparing by conformal avoidance intensity-modulated radiation therapy for anal cancer: dosimetric evaluation of coverage of pelvis and inguinal/femoral nodes. Int J Rad Oncol Biol Phys2005;63:274281.

    • Search Google Scholar
    • Export Citation
  • 54.

    MyersonRJGarofoloMCNaqaIE. Elective clinical target volumes for conformal therapy in anorectal cancer: an Radiation Therapy Oncology Group Consensus Panel Contouring Atlas. Int J Radiat Oncol Biol Phys2008;74:824830.

    • Search Google Scholar
    • Export Citation
  • 55.

    HoffmanRWeltonMLKlenckeB. The significance of pretreatment CD4 count on the outcome and treatment tolerance of HIV-positive patients with anal cancer. Int J Radiat Oncol Biol Phys1999;44:127131.

    • Search Google Scholar
    • Export Citation
  • 56.

    FraunholzIWeissCEberleinK. Concurrent chemoradiotherapy with 5-fluorouracil and mitomycin C for invasive anal carcinoma in human immunodeficiency virus-positive patients receiving highly active antiretroviral therapy. Int J Radiat Oncol Biol Phys2009;in press.

    • Search Google Scholar
    • Export Citation
  • 57.

    ChiaoEYGiordanoTPRichardsonPEl-SergHB. Human immunodeficiency virus-associated squamous cell cancer of the anus: epidemiology and outcomes in the highly active antiretroviral therapy era. J Clin Oncol2008;26:474479.

    • Search Google Scholar
    • Export Citation
  • 58.

    SeoYKinsellaMTReynoldsHL. Outcomes of chemoradiotherapy with 5-fluorouracil and mitomycin C for anal cancer in immunocompetent versus immunodeficient patients. Int J Radiat Oncol Biol Phys2009;75:143149.

    • Search Google Scholar
    • Export Citation
  • 59.

    Oehler-JanneCHuguetFProvencherS. HIV-specific differences in outcome of squamous cell carcinoma of the anal canal: a multicentric cohort study of HIV-positive patients receiving highly active antiretroviral therapy. J Clin Oncol2008;26:25502557.

    • Search Google Scholar
    • Export Citation
  • 60.

    KlenckeBJPalefskyJM. Anal cancer: an HIV-associated cancer. Hematol Oncol Clin North Am2003;17:859872.

  • 61.

    FaivreCRougierPDucreuxM. 5-fluorouracil and cisplatinum combination chemotherapy for metastatic squamous-cell anal cancer. Bull Cancer1999;86:861865.

    • Search Google Scholar
    • Export Citation
  • 62.

    NigroND. An evaluation of combined therapy for squamous cell cancer of the anal canal. Dis Colon Rectum1984;27:763766.

  • 63.

    CummingsBJKeaneTJO'SullivanB. Epidermoid anal cancer: treatment by radiation alone or by radiation and 5-fluorouracil with and without mitomycin C. Int J Radiat Oncol Biol Phys1991;21:11151125.

    • Search Google Scholar
    • Export Citation
  • 64.

    MullenJTRodriguez-BigasMAChangGJ. Results of surgical salvage after failed chemoradiation therapy for epidermoid carcinoma of the anal canal. Ann Surg Oncol2007;14:478483.

    • Search Google Scholar
    • Export Citation
  • 65.

    RenehanAGSaundersMPSchofieldPFO'DwyerST. Patterns of local disease failure and outcome after salvage surgery in patients with anal cancer. Br J Surg2005;92:605614.

    • Search Google Scholar
    • Export Citation
  • 66.

    DasPBhatiaSEngC. Predictors and patterns of recurrence after definitive chemoradiation for anal cancer. Int J Radiat Oncol Biol Phys2007;68:794800.

    • Search Google Scholar
    • Export Citation
  • 67.

    NilssonPJSvenssonCGoldmanSGlimeliusB. Salvage abdominoperineal resection in anal epidermoid cancer. Br J Surg2002;89:14251429.

  • 68.

    AllalASLaurencetFMReymondMA. Effectiveness of surgical salvage therapy for patients with locally uncontrolled anal carcinoma after sphincter-conserving treatment. Cancer1999;86:405409.

    • Search Google Scholar
    • Export Citation
  • 69.

    EllenhornJDEnkerWEQuanSH. Salvage abdominoperineal resection following combined chemotherapy and radiotherapy for epidermoid carcinoma of the anus. Ann Surg Oncol1994;1:105110.

    • Search Google Scholar
    • Export Citation
  • 70.

    SchillerDECummingsBJRaiS. Outcomes of salvage surgery for squamous cell carcinoma of the anal canal. Ann Surg Oncol2007;14:27802789.

    • Search Google Scholar
    • Export Citation
  • 71.

    ChessinDBHartleyJCohenAM. Rectus flap reconstruction decreases perineal wound complications after pelvic chemoradiation and surgery: a cohort study. Ann Surg Oncol2005;12:104110.

    • Search Google Scholar
    • Export Citation
  • 72.

    CummingsBJKeaneTJO'SullivanB. Metastatic anal cancer: the search for a cure. Onkologie2006;29:56.

  • 73.

    AjaniJACarrascoCHJacksonDEWallaceS. Combination of cisplatin plus fluoropyrimidine chemotherapy effective against liver metastases from carcinoma of the anal canal. Am J Med1989;87:221224.

    • Search Google Scholar
    • Export Citation
  • 74.

    JaiyesimiIAPazdurR. Cisplatin and 5-fluorouracil as salvage therapy for recurrent metastatic squamous cell carcinoma of the anal canal. Am J Clin Oncol1993;16:536540.

    • Search Google Scholar
    • Export Citation
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 571 571 22
PDF Downloads 32 32 4
EPUB Downloads 0 0 0