Anal Canal Cancer: Overview

Anal Canal Cancer

• Anal canal cancer is a relatively rare digestive cancer with typically slow locoregional evolution.
• The majority of cases are epidermoid carcinomas.
• First-line treatment is conservative.

General Information

• Anal canal cancer is defined as a malignant cellular proliferation developed from the epithelium of the anal canal.
• Anal canal cancers are rare, accounting for 1.5% of digestive cancers.
• Diagnosis is clinical, involving a rectal exam, and is confirmed histologically by biopsy.
• Anal canal tumors respond well to radiotherapy and chemotherapy.
• Prognosis depends on the stage at diagnosis and management.
• The anal canal is in the median part of the posterior perineum, below the levator ani muscles, between the ischiorectal fossae.
• It's a 3-4 cm long cylinder extending from the pelvic diaphragm to the anal orifice.
• The anal canal opens through the anus at its lower part.

Vascularization

• The superior rectal artery, a terminal branch of the inferior mesenteric artery, supplies blood.
• The middle and inferior rectal arteries, both collateral branches of the internal pudendal artery, also supply blood.
• Lymphatic drainage occurs through two main pathways: one ascending towards the rectal lymphatics and one descending towards the inguinal lymph node chains.

Epidemiology

• Anal canal cancer is rare; its frequency is much lower than that of colorectal cancers, accounting for 3% of all cancers in the lower digestive tract.
• Typical age of onset is older, with the average age being 62 years.
• Incidence is 1.5 per 100,000 people, increasing with age after 40.
• There is a higher incidence in homosexual and bisexual men.
• There is a gender predominance in women, with a sex ratio of 1.5 to 3.

Predisposing Factors

• HPV (Human papilloma virus) is a sexually transmitted agent responsible for anal condylomatosis and acts as an oncogenic virus that leads to dysplasia.
• A history of cervical cancer increases risk, with a relative risk (RR) of *10.
• Immunodepression: The risk of anal cancer is high in transplant recipients and those infected with HIV.
• Tobacco use increases risk, with an RR of *1.9 after 20 pack-years.
• Homosexual activity, particularly passive anal sex, increases risk.
• HIV, and multiple sexual partners increases risk.

Anatomopathology

• Macroscopic forms include:
  • Vegetative
  • Ulcerated (less radiosensitive)
  • Infiltrating (stenotic)
• Epidermoid carcinomas: most common (60-80%), originating from the malpighian mucosa that covers about 3/4 of the anal canal.
• Cloacogenic or transitional carcinomas: 8-10% of anal canal cancers, arising from transitional mucosa.
• Adenocarcinomas: originate from the glandular mucosa lining the upper part of the canal.
• They can be challenging to distinguish from rectal adenocarcinomas with canal extension, accounting for 7-9% of anal canal cancers and responding less well to radiotherapy than epidermoid carcinomas.
• Malignant melanomas: occur in approximately 1% of anal cancers and typically have poor prognoses due to delayed diagnosis.
• Hodgkin’s and non-Hodgkin’s lymphomas: rare and usually associated with acquired immunodeficiency syndrome (AIDS).

Signs

• Revealing symptoms are generally non-specific
• Rectal bleeding occurs in 40-50% of cases, often of low abundance.
• Pain varies in intensity depending on sphincter involvement.
• Anal burning and pruritus ani can be significant symptoms.
• A palpable mass may be present.
• Changes in bowel habits can occur.
• Rarely, patients may experience tenesmus, false needs, anal incontinence, or rectovaginal fistula, indicating advanced disease.
• Unilateral inguinal mass with recent onset may indicate inguinal adenopathy.
• General signs include:
  • General health deterioration
  • Weight loss
  • Asthenia
  • Anemia
  • Fever

Physical Signs

• Inspection of the anal region is done after unfolding the radial folds to differentiate cancer of the anal margin from anal canal cancer with extension to the margin.
• Digital Rectal Exam assesses:
  • Friability of the tissue
  • Tumor size (height, width, thickness) in centimeters
  • Lesion topography, especially extension to the lower rectum
  • Circumferential involvement
  • Degree of canal stenosis
  • Sphincter involvement detection is difficult
  • Regional infiltration towards the rectovaginal septum in women and the prostate in men, and laterally to the ischiorectal fossae
  • Presence of hard, pararectal, or pelvic lymph node nodules, with examination of inguinal areas
  • Hepatomegaly
  • Troisier’s node.

Paraclinical Signs

• Anuscopy:
  • It visualizes the lesion and allows creation of a map, enabling multiple deep biopsies essential for diagnosis and histological typing.
    • Early-stage: a small nodule or ulceration of a fold with associated induration as a significant sign of malignancy.
    • Advanced stage: three macroscopic aspects:
      • Predominantly vegetative tumors extending basally into the rectum or anal margin,.
      • Ulcerations bordered by indurated edges.
      • Infiltrating forms extending circumferentially, causing more or less important anal canal stenosis.
  • Echoendoscopy: good sensitivity in detecting adenopathies in the rectal sheath and deep adenopathies
  • It is mostly useful in overweight patients and can guide diagnostic aspiration biopsies.
  • Abdominopelvic CT scan: helpful
  • It is used for large tumors where extension and presence of suspicious adenopathies in iliac areas as well as pelvic extension are determined
• MRI:
  • It is accurate for pelvic extension and adenopathy existence
• Tumor markers: controversial utilization:
  • SCC tumor antigen 4 (SCC TA 4)
  • Cytokeratin fragment 21-1 (CYFRA 21-1)

Clinical Forms

• Symptomatic forms: stenosing anal canal cancer presents with an occlusive pattern
• Forms depending on the field: anal canal cancer in men has an increasing global incidence.
• Forms depending on the field: anal canal cancer patients are younger than 35
• Associated forms: tumors associated with an underlying pathology complicate the clinical picture and often render the patient inoperable, examples:
  • Cardiac insufficiency
  • Cirrhosis
  • Respiratory failure
  • Renal insufficiency

Diagnosis

• Positive diagnosis: is based on revealing signs and rectal examination, supported by anuscopy and confirmed by anatomical pathology examination.
• Differential diagnoses:
  • Hemorrhoidal thrombosis
  • Anal fissure
  • Syphilitic or tuberculous ulcer
  • Anal margin abscess
  • Ischio rectal space abscess
• Extension diagnosis:
  • Echoendoscopy is used to evaluate extension towards the internal and external sphincters and assess lymph node involvement.
  • Abdomino-pelvic CT scan is used to evaluate iliac and lumboaortic lymph nodes and detect liver lesions.
• Extension mode is either:
  • LOCAL: contiguity with organs and adjacent structures.
  • LYMPHATIC: cancer with strong lymph node involvement.
  • METASTATIC: rare at diagnosis, less than 10%.
  • Preferential localization in liver (5-8%), lungs (2-4%), bones (2%) and skin.

TNM Classification

• (T) Primary Tumor
  • Tx - unevaluable
  • Tis - Tumor in situ
  • T0 - no primary
  • T1 - less than 2cm
  • T2 - 2cm - 5cm
  • T3 - greater than 5cm
  • T4 - invades adjacent organs
• (N) Regional Lymph Nodes
  • Nx - unevaluable
  • N0 - no suspect adenopathy
  • N1 - perirectal adenopathy
  • N2 - perirectal + inguinal/iliac adenopathy
  • N3 - perirectal + bilateral inguinal/iliac adenopathy
• (M) Metastasis
  • Mx - unevaluable
  • M0 - no metastasis
  • M1 - metastasis present

Treatments

• Aims to improve the vital prognosis of the patient, remove the tumor, and avoid complications and recurrence.
• Medical treatments include:
  • Exclusive Chemotherapy:
    • Standard Regimen: 5-Fluorouracil (600 to 1000 mg/m2 from J1 to J4 or J5) and Mitomycin C (10 to 15 mg/m2 at J1), repeated every 28 days.
    • Alternative Regimen: 5-Fluorouracil (600 to 1000 mg/m2 from J1 to J 4 or J5) and CIS DDP (80 to 100 mg/m2 in a single injection or over 5 days).
  • Exclusive Radiotherapy: Done in two steps:
    • External pelvic radiotherapy (tumor and ganglion), 45 to 50 Gy, followed after a interval of 2-3 weeks.
    • Local boost with external radiotherapy (tumor) 15 to 20 Gy or interstitial curietherapy.
  • Concomitant Radio-Chemotherapy: associates an external pelvic radiotherapy (45 Gy in 25 fractions and 5 weeks) and a concomitant chemotherapy during the first week and the fifth week according to 5 FU – MITO, or 5FU-CDDP protocol.
  • Radio-surgical treatment: Pelvic radiotherapy or radio-chemotherapy is followed by an abdomino-perineal amputation after 6 weeks.
• Surgical treatments include:
  • Local Excision: reserved for in situ tumors less than 1 cm that are incidentally discovered during hemorrhoidectomy
  • Ano-Rectal Amputation: Performed through the abdomino-perineal route with superior, middle, and inferior hemorrhoidal lymph node dissection.
  • Used as second line after failure of conservation treatment;

Surgical Indications

• Necessity Inguinal Dissection: intentionally limited in presence of suspicious lymphanopathy.
• It can be done before or after radiation;
• Transitory or definitive Colostomy.
• Tis Stage: excision is enough
• T1N0 Stage: reference = radiotherapy or surgery if less than 1cm
• Indication based on stage
  • T2N0: Radiotherapy -T3 or T1-T2N1-N3: Radio-chemotherapy; surgery reserved if not efficient
  • T4: depends on extension, response to treatment; aim for continent
  • Metastatic: chemotherapy

Type of Surgery

• Amputation: reserved for failure of conservative treatments & radioresistance and necrosis
• Inguinal - if diagnostic and for recurrence
• Excision - for T1 less than 1cm
• Colostomy - may be transitional to allow for post operative healing, or may be permanent

Post treatment complications

• Non debilitating : occurs because of radiotherapy
  • Telangiectasia - skin condition
  • Sclerosis of perineum
  • Pubic edema
• Debilitating:
  • Rectal bleeding
  • Rectitis - inflammation of rectum
  • Sclerosis causing transit alteration of the rectum
  • Reoccuring cystitis - bladder inflammations
  • Can cause removal of ovaries
• Debilitating can indicate surgical intervention
  • Intestinal occlusions
  • Vaginal fistulas - spontaneous closing is exceptional
  • Stenois and possible occlusion

Surveillance

• Frequent checks for two years after recovery to prevent reoccurence
• Semi annual for three years
• Annual after

Prognosis

• Five year survival rate is 66-78%
• Factors:
  • Age/Gender/Size/Ganglion size, whether its metastatic

Conclusion

• Rare disease which is has increased
• Initial symptoms are weak or non-apparent and only becomes frequent with advanced symptoms
• Diagnosis is by rectal and histology
• Higher chances of recovery by radio treatment with chemotherapy for lesions
• Surgery is for tumors which dont respond other treatments well