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A. Characteristics navigator

  1. Relatively uncommon tumor, usually of squamous epithelium
    1. Tumors arising within anal canal distal to dentate like usually keratinizing
    2. Tumors arising proximal to dentate line usually nonkeratinizing
    3. Two nonkeratinizing subtypes are transitional cell and cloacogenic
    4. These two subtypes behave similarly
  2. About 3400 new cases in year 2000 (1.9% of colorectal cancers)
  3. Human papilloma virus (HPV) [2]
    1. HPV is the most common causative agent
    2. HPV found in anal cancers from women more commonly than men
    3. In one recent study, any HPV serotypes found in 69% of female and 93% of male anal Ca
    4. Etiology of cervical cancer parallels that of anal cancer
    5. Thus, >75% of anal cancers are positive for HPV serotype 16
  4. HIV+ Persons [3,4]
    1. At highly increased risk for HPV associated anal cancer
    2. HPV may be acquired in the absence of anal intercourse in HIV+ anal cancer or precursors
    3. HIV+ persons with CD4+ counts <500/µL should be considered for anal cytologic screening

B. Risk Factors navigator

  1. Perianal fissures, fistulas or hemorrhoids are NOT risk factors [1]
  2. Presence of Condylomata accuminata (anogenital warts)
    1. Anogenital warts are nearly always due to HPV infection
    2. Presence of warts is a marker for HPV infections
    3. Multiple serotypes of HPV are usually found in patients with anal cancers
    4. In the majority of cases, these were high risk HPV serotypes (61% F and 88% M)
  3. Anal Squamous Intraepithelial Lesions (ASIL) [5]
    1. Precursor to frank anal carcinoma
    2. Strongly associated with oncogenic HPV serotypes
    3. Pap-smear like screening for ASIL is cost-effective in HIV+ men at risk
  4. Receptive Anal Intercourse
    1. Homosexual males
    2. Females receptive to anal intercourse
    3. Clearly related to HPV transmission in HIV+ men
  5. Leukoplakia
  6. History of sexually transmitted diseases
  7. More than 10 sex partners (probably related to HPV infection)
  8. History of cervical, vulvar, or vaginal cancer (probably related to HPV infection)
  9. Immunosuppression
    1. Increased risk with HIV positivity
    2. However, in HIV, anal cancer risk is not dependent on degree of immunosuppression [4]
    3. Solid organ transplantation related immunosuppression
  10. Smoking appears to be a 2-5 fold risk factor

C. Symptoms navigator

  1. Retal bleeding - most common symptom (~45% of cases)
  2. Rectal pain or sensation of mass (~35% of cases)
  3. Painful defacation (tenesmus) - minority
  4. About 20% have no rectal symptoms
  5. About 50% have a history of anogenital warts

D. Pathologynavigator

  1. About 65% of tumors are derived from squamous cells (distal to pectinate line)
  2. Carcinomas proximal to pectinate line (~35%)
    1. Gasaloid
    2. Cuboidal (transitional cell)
    3. Cloacogenic
    4. These behave similarly to the distal squamous anal cancers
  3. Lymphatic Drainage and Lymphadenopathy
    1. Drainage above dentate line to perirectal and paravertebral nodes
    2. Drainage below dentate line is through inguinal and femoral nodes
  4. Prognostic Factors
    1. Tumor size is most important
    2. Tumors <2cm have >90% 5 year survival
    3. Tumors >5cm have <50% 5 year survival
    4. Patients with positive lymph nodes, regardless of size, have ~50% 5 year survival
  5. Overall survival is >65% at 5 years

E. Treatmentnavigator

  1. Surgery
    1. Previously, radical surgery was used and necessitated permanent colostomy
    2. Local surgery is now primarily used, particularly for large masses
    3. Often combined with other modalities including radiotherapy
    4. Abdominoperineal resection is treatment of choice for recurrent disease
  2. Local high dose radiation therapy is now standard
    1. High dose external-beam therapy reduces recurrences >50%
    2. Often combined with intersitital irradiation
    3. This interstitial radiation, or brachytherapy, is by implantation of radioactive beads
    4. Local control and cures found in 70-90% of selected (node negative, <5cm tumors) cases
    5. Radiotherapy with hyperthermia may improve outcomes locally advanced rectal cancer [6]
    6. Side effects include anal ulcers, stenosis, and necrosis
    7. Colostomy may be required in ~10% of cases
  3. Chemotherapy [1,7]
    1. Typically added to radiation therapy
    2. Improves overall survival in some studies but not others [8]
    3. Typically 5-fluorouracil (5-FU) with mitomycin
    4. Mitomycin improved disease-free but not overall survival
    5. Platinum agents (cisplatin) may be used second line
    6. Cisplatin+5-FU had inferior disease free survival and more failed colostomies than standard mitomycin+5-FU all with radiotherapy for first line therapy [9]
    7. Pre- or post-operative 5-FU/leucovorin chemotherapy added to radiotherapy reduced local recurrences of operable T3/T4 rectal cancer but did not affect overall survival [8]
  4. Adjuvant chemotherapy had higher early mortality but overall same survival as radiation
  5. Combination of modalities is recommended for initial therapy
    1. Distal metastases usually occur in liver
    2. In patients receiving combination therapies, 10-17% develop distal metastases

References navigator

  1. Ryan DP, Compton CC, Mayer RJ. 2000. NEJM. 342(11):792 abstract
  2. Frisch M, Glimelius B, van den Brule AJC, et al. 1997. NEJM. 337(19):1350 abstract
  3. Piketty C, Darragh TM, Da Costa M, et al. 2003. Ann Intern Med. 138(6):453 abstract
  4. Goedert JJ, Cote TR, Virgo P, et al. 1998. Lancet. 351(9119):1833 abstract
  5. Goldie SJ, Kuntz KM, Weinstein MC, et al. 1999. JAMA. 281(19):1822 abstract
  6. Van der Zee J, Gonzalez DG, van Rhoon GC, et al. 2000. Lancet. 355(9120):1119
  7. Drugs of Choice for Cancer Chemotherapy. 2000. Med Let. 42(1087):83
  8. Bosset JF, Collette L, Calais G, et al. 2006. NEJM. 355(11):1114 abstract
  9. Ajani JA, Winter KA, Gunderson LL, et al. 2008. JAMA. 299(16):1914 abstract