Vaginal Cancer

Epidemiology

  • Age range is 50-70 years.
  • 1-2% of all gynecological cancers.
  • HPV, previous hysterectomy, previous RT, gynecological tumors are risk factors for VC
  • Clear cell adenocarcinoma of the vagina is associated with DES exposure in-utero (1/1000 exposed) and occurred in younger patients.

Pathology

  • CIS can involve multiple vaginal regions but the most common is the upper 1/3.

Malignant Tumors by Frequency

SCCA 80%-90%
Adenocarcinoma 5%
Melanoma 3%
Sarcoma:
* leiomyosarcoma - 66%
* RMS - children
3%
  • Benign differential: condyloma, endometriosis, VAIN, adenosis
  • Metastatic differential: cervix, vulva, urethra, bladder, rectum, endometrium, ovary

Anatomy

  • Vaginal mucosa has SSCA covers the fibromuscular wall measuring less than 5mm thick.
  • Submucosa is composed of loose network of vessels and lymphatic channels and elastic fibers.
  • The proximal vagina has greater tolerance to RT than the more distal vagina.

Presentation

  • 50% involves the upper 1/3 of the vagina fairly evenly distributed (anterior/posterior/lateral).
  • The most common symptom is vaginal bleeding, discharge, mass, post coital bleeding, urinary symptoms and pelvic pain. Present on the average 7.4 months of symptoms before diagnosis.
  • Routes of Spread:
  1. Local: Invade vaginal wall and into the musculature, urogenital diaphragm , parametria, levator ani muscles, pelvic sidewall, rectum, and bladder.
  2. Lymphatics: Channels run along the submucosal and muscular layers. The upper vagina 2/3 drains to the paracervical, obturator, hypogastric, external iliac, and common iliac nodes. The lower 1/3 vagina drains to the inguinal, femoral, and the external iliac nodes. The posterior wall drains to the pararectal and deep pelvic nodes. The anterior wall drains to the internal iliacs.

Prognostic factors

  • Stage
  • Extent of vaginal canal involvement: DFS(5y) <1/3 (61%) >1/3 (25%)
  • Lymph node status
  • Tumor grade, size, and depth of invasion
  • Radiotherapy Dose
  • Overall Treatment Time
  • Location of lesion: Upper lesions do better. 5y survival for upper (60%), middle (37.5%), lower (37%).

Diagnosis

  • H/P with EUA, colposcopy with biopsy of both tumor and cervix, CXR, CT scan of pelvis/abdomen (not used in FIGO staging), Liver and renal functions, CBC with diff, sigmoidoscopy, cystoscopy.
  • If a vaginal tumor involves either the vulva or cervix, it is staged as one of later tumors.
  • Also, if a vaginal mass is discovered within 10 years of another diagnosis then it is considered as metastases.

Staging and Outcome

AJCC Stage

Stage Description Nodal incidence 5-OS
0 Carcinoma in situ 90%
I Confined to vagina(T1) 0-6% 77%
II Invades parametrial tissues(T2) 20-25% 56%
III Extends to the pelvic sidewall(T3)
OR regional LN(N1)
75% 39%
IVA Invades the bladder/rectum;beyond the true pelvis 85% (IVA & IVB) 20%
IVB Distant metastasis 0%
  • N1: pelvic or inguinal LN metastasis

FIGO Staging

  • FIGO staing of disease associated with inguinal lymph nodes are somewhat ambiguous.
  • FIGO stage III: Lymph nodes are not considered.
  • FIGO stage IV/ Stage IVA: It may or may not have spread to lymph nodes.
  • Stage IVB: Not in FIGO.
  • Pattern of Recurrence
    • Locoregional is most common failure at 85%.
    • Distant failure is 7-33%.

Guidelines

  • Stage O: (NED 90%):
    • Surgical excision, cryotherapy, laser
    • RT (vaginal cylinder alone x2 to dose of 6o-75Gy) is preferred.
  • Stage I very small (<1cm):
    • Implant alone or surgery can be done for
    • Surgery not better than XRT, and more sexual dysfunction due to removal of more tissue.
  • Stage I/II/III/IV:
    • EBRT (45-50Gy) + implant (20-30Gy) for total dose of
      • 75-85 Gy to vaginal surface (for superficial tumors)
      • 75-85 Gy to tumor volume + 0.5 cm (for deeper lesions)
  • Stage III & IV (Lamoreaux)
    • Consider cisplatin based chemoradiation based on cervix and vulvar literature (ie. treat with EBRT alone)
    • Treat inguinal for lower 1/3 vagina
    • Boost node+ to 60 Gy
  • Stage IV
    • Brachytherapy may be avoided due to concern for fistula. In this case chemRT alone.

Therapy based on location of the Tumor

Treatment

Surgery

  1. Varies from local excision to total exenteration.
  2. Anterior Exenteration: remove vagina, bladder, urethra
  3. Posterior Exenteration: remove vagina, rectum
  • While most patients are treated with RT surgery is considered in the following:
    • CIS-VAIN and early stage I located in the upper or distal 1/3 of vagina in selected young women
    • younger women with desire to preserve ovarian or vaginal function.
    • verrucous carcinoma, nonepithelial tumors and failures after radiation

Chemotherapy

  • Not found to be effective for VC

External Beam Radiation therapy

  • Most common treatment includes EBRT 45-50 Gy + implant.
  • Use 4 field pelvic technique with electron boost to the inguinal region.
    • Superior border is L5-S1 interspace,
    • the inferior border should include the entire vagina,
    • and laterally 1.5-2.0 cm past pelvic brim.
    • The inguinal nodes lie beneath and inferior to the inguinal ligament which runs between the anterior iliac spine and the pubic tubercle. Mark the lesion with seed.

Brachytherapy 70-85 Gy total

  • Dose may be prescribed to vaginal mucosa (for superficial tumors < 5 mm) or at depth to tumor volume (for deep tumors)
  • Intracavitary: The vaginal cylinders with a central tandem include the Bloedorn, Burnett, and Delclos (Cs137) and are used for superficial lesions.
  • Interstitial: The 2 most common used applicators are the Syed and the MUPIT (multiple perineal applicator) where a tandem is used if uterus is still in place. The goal is to cover the tumor volume with a 1-2 cm margin. I-192 ribbons are used. The dose rate should be 50-60 cgy/hr.

Needle Implants

General Notes

  • Parametrial Implant Boost
  • Dose:
  • 50 GY EBRT,
  • volume Implant 5 to volume to cover tumor
  • Respect bladder/rectal tolerance

Technique (Free Hand) for Lesions > 5 mm in depth

  • For upper vaginal tumors
    • Insert foley catheter, and injecting methylene blue into the bladder
    • Laparoscopic guidance reduce abdominal viscera
  1. Place needles such that tumor volume + 1-2cm is implanted.
  2. Guide needle with finger in rectum
  3. Cogniscent of bladder and rectum
  4. Insert vaginal cylinder
  5. Post-implant cystoscope post implant and rectal exam.
  6. After load I-192

Vaginal Surface Dose Tolerance In Thirds

Radiation Injury:

  • vaginal stenosis
  • cystitis
  • proctitis
  • fistula
  • vaginal necrosis (4-16%, especially doses up to 140 Gy in the upper vagina and 98 Gy for the lower vagina).
Bibliography
1. Hintz BL, Kagan AR, Chan P, Gilbert HA, Nussbaum H, Rao AR, Wollin M.Radiation tolerance of the vaginal mucosa. Int J Radiat Oncol Biol Phys. 1980 Jun;6(6):711-6. No abstract available. PMID: 7451275
2. Au SP, Grigsby PW. The irradiation tolerance dose of the proximal vagina. Radiother Oncol. 2003 Apr;67(1):77-85. PMID: 12758243
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