Anal Cancer

Aka: Anal Cancer, Anorectal Malignancy

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II. Epidemiology

  1. Rare malignancy (0.5% of all cancers in U.S., 2% of gastrointestinal cancers)
    1. Incidence: 9760 (in U.S. 2023, accounted for 0.5% of all new cancers)
    2. Deaths: 1870 (in U.S. 2023, accounted 0.3% of all cancer deaths)
  2. Gender
    1. Higher Incidence in women by Factor X2-3
  3. Age
    1. Overall peak age: 35 to 49 years
    2. Women age >50 to 64 years (esp. >65 years)

III. Risk Factors

  1. HPV Infection (>80% of cases, esp. HPV16)
    1. Coincides with increased Anal Cancer risk in women with CIN 3 or Cervical Cancer
    2. Genital Wart history also associated
  2. Sexually Transmitted Infection and Related Risks
    1. HIV Infection (aside from HPV, highest risk for Anal Cancer, esp. in MSM)
    2. Anal Intercourse
    3. Increased number of sexual partners
    4. Men who have Sex with Men (MSM)
  3. Immunocompromised States
    1. Solid Organ Transplant recipient
    2. Autoimmune disorders (e.g. SLE, Inflammatory Bowel Disease)
  4. Other risks
    1. Tobacco Abuse

IV. Types

  1. Anal Squamous Cell Carcinoma (ASCC, 80% of Anal Cancers)
    1. ASCC develops at the squamous to columnar epithelial junction
    2. Associated with several specific genetic mutations
  2. Anal adenocarcinoma (5-10% of Anal Cancers)
    1. Staged as ASCC, but treated as Colorectal Cancer (e.g. chemoradiation followed by resection)
  3. Other uncommon to rare Anal Cancers
    1. Lymphoma
    2. Gastrointestinal Stroma tumors
    3. Melanoma
    4. Neuroendocrine tumors

V. Precautions

  1. Delayed presentation is common >6 months (e.g. social stigma)
  2. Initial misdiagnosis is common (e.g. Hemorrhoids)

VI. Symptoms

  1. Often asymptomatic
  2. Rectal Bleeding
  3. Fecal Incontinence (or anal leakage)
  4. Pruritus Ani
  5. Anorectal Pain
  6. Anal or rectal mass Sensation
  7. Anal canal tissue prolapse

VII. Signs

  1. Rectal lesion (may be palpable)
  2. Fecal Occult Blood (may be positive)
  3. Inguinal Lymph Nodes (may be palpable)
  4. Anoscopy may be performed (or deferred to surgeon)

VIII. Differential Diagnosis

  1. See Lower Gastrointestinal Bleeding
  2. See Anorectal Pain
  3. Anal Lesions
    1. Anal Fissure
    2. Anal Fistula
    3. Hemorrhoids
    4. Condyloma acuminata (Genital Wart)
    5. Chancroid
    6. Psoriasis

IX. Labs

  1. Complete Blood Count (CBC)
  2. Comprehensive metabolic panel
  3. HIV Test
  4. HPV Testing (anal)
  5. Pap Smear and HIV Testing (women)

X. Diagnostics

  1. Anal mass biopsy or fine needle aspirate
    1. Tissue diagnosis
  2. Advanced Imaging
    1. Evaluate for local and metastatic disease
    2. Imaging per surgery and oncology recommendations
      1. Staging CT/PET
      2. Phased-array pelvic MRI

XI. Staging: TNM

  1. Tumor (T)
    1. T0: No tumor evidence
    2. Tis: HGSIL or carcinoma in situ
    3. T1: Tumor <= 2 cm
    4. T2: Tumor >2 to 5 cm
    5. T3: Tumor >5 cm
    6. T4: Any tumor size invading adjacent organs (e.g. vagina, Urethra or Bladder)
  2. Lymph Node (N)
    1. Nx: Lymph Nodes not assessed
    2. N0: No regional Lymph Node involvement
    3. N1: Node involvement (node metastases)
      1. N1a: Inguinal, mesorectal, or internal iliac node involvement
      2. N1b: External iliac node involvement
      3. N1c: External iliac node AND any N1a node involvement
  3. Metastases (M)
    1. M0: No distant metastases
    2. M1: Distant Metastases
  4. Overall Staging
    1. High Grade Intraepithelial Lesion (Carcinoma In-situ, Bowen's Disease)
      1. Stage 0: TisN0M0
    2. Localized Anal Cancer
      1. Stage 1: T1N0M0
      2. Stage 2a: T2N0M0
      3. Stage 2b: T2N0M0
    3. Advanced Anal Cancer
      1. Stage 3a: T1-2N1M0
      2. Stage 3b: T4N0M0
      3. Stage 3c: T3-4N1M0
    4. Metastatic Anal Cancer
      1. Stage 4: M1, with any T and any N

XII. Management: Anal Cancer

  1. Chemoradiation Therapy (CRT)
    1. CRT is the mainstay of treatment for Anal Cancer (Chemotherapy combined with external beam radiation)
    2. Specific regimens are per oncology, but common regimens are listed here as of 2024
      1. Localized and Advanced Cancer: Fluorouracil (5FU) and Mitomycin C (MMC)
      2. Metastatic Anal Cancer: Carboplatin and Paclitaxel
  2. Surgery
    1. Chemotherapy and radiation have largerly replaced surgical management since the 1970s
    2. However, local excision may be considered in Stage 1 Anal Cancer
    3. Salvage abdominal perineal resection may also be considered for recurrent disease
  3. Immunotherapy
    1. Immune Checkpoint Inhibitor (e.g. PD-1 Monoclonal Antibody, PDL-1 Monoclonal Antibody)
      1. Used in some cases of advanced Anal Cancer and metastatic Anal Cancer

XIII. Management: High Grade Intraepithelial Lesion (HGSIL, Carcinoma In-situ, Bowen's Disease)

  1. Surveillance without treatment has historically been an option, but is no longer recommended
    1. Outcomes are significantly better with local treatment of HGSIL
    2. Palefsky (2022) N Engl J Med 386(24):2273-82 +PMID: 35704479 [PubMed]
  2. Treatment protocols
    1. Lesion ablation (e.g. Infrared Coagulation, electrocautery, laser) with or without excision
    2. Topical treatments (Imiquimod and Fluorouracil)

XIV. Prevention

  1. Human Papilloma Virus Vaccine (Gardasil)

XV. Resources

  1. Anal Cancer (Stat Pearls)
    1. https://www.ncbi.nlm.nih.gov/books/NBK441891/

XVI. References

  1. Gondal (2023) Curr Oncol 30(3):3232-50 +PMID: 36975459 [PubMed]

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