Treatment Protocols
Primary vaginal cancer is a rare disease of the female genital tract. American Cancer Society estimates for 2017 are for 4810 new cases and 1240 deaths.
The histology of vaginal cancers is most commonly squamous cell, followed by adenocarcinoma. Other histologies (eg, vaginal melanoma, sarcomas, clear cell carcinoma, and lymphoma) can also be identified as primary lesions in the vagina.
This article focuses on treatment of squamous cell and adenocarcinoma histologies and does not include the management of vaginal dysplasia or vaginal carcinoma in situ.
General principles of treatment
There are no official treatment guidelines for vaginal cancer, and most published data are derived from small retrospective studies. General principles are as follows:
The location of disease, the size of the lesion, and the clinical stage of the tumor should help guide treatment planning
Stage I and II disease with squamous cell lesions at the apex or the upper posterior or lateral portions of the vagina may be treated surgically
Definitive radiation therapy has largely replaced surgery as the primary therapeutic modality in vaginal cancer; because of anatomic constraints, achieving a wide negative surgical margin may not be possible without performing a radical surgical procedure such as exenteration
External-beam radiation therapy (EBRT) is recommended in patients with stage I poorly differentiated tumors and deeply invasive lesions and in all patients with stage II-IV disease
Surgical management that does not result in adequate margins mandates adjuvant radiation therapy
Concurrent cisplatin-based chemotherapy should be considered in conjunction with radiation therapy
Treatment recommendations for stage I disease (small superficial lesions < 2 cm and < 0.5 cm thick)
Surgery
Small lesions in the apex, the upper posterior portion, or the upper lateral third of the vagina can be treated with wide local excision. Bilateral pelvic lymph node dissection can be performed. Adjuvant radiation therapy should be used to treat margins that are positive or close to the resection bed.
Intracavitary radiation therapy
Lesions in the middle and distal portions of the vagina are usually treated with radiation. Doses of 60-70 Gy are delivered to the entire vagina to a depth of 0.5 cm. An additional 20- to 30-Gy dose is delivered to the tumor bed.
Treatment recommendations for stage 1 disease (larger, deeper lesions >2 cm or >0.5 cm thick)
Surgery
Radical hysterectomy and pelvic lymphadenectomy can be performed for lesions in the apex, the upper posterior portion, or the upper lateral third of the vagina. Radical vaginectomy is performed if the patient has previously undergone hysterectomy.
Skin grafting or reconstruction of a neovagina may be performed. For lesions located in the lower third of the vagina, vulvovaginectomy may be necessary to achieve negative margins. An inguinal-femoral lymphadenectomy should be performed if lesions involve the lower third of the vagina.
Close or positive surgical margins should be treated with adjuvant radiation therapy.
Interstitial and intracavitary radiation therapy
Most lesions in the middle and distal portions of the vagina are treated with both interstitial and intracavitary radiation therapy. Such an approach allows treatment to an adequate depth without overtreatment of the vaginal mucosa. The intracavitary dose delivers 60-65 Gy to the vaginal mucosa, the dose to 0.5 cm is calculated, and an additional 15-20 Gy is then delivered 0.5 cm beyond the implant. The base of the tumor receives approximately 65-70 Gy, and the vaginal mucosa receives 80-120 Gy.
Additional EBRT is suggested for poorly differentiated or infiltrating tumors.
For lesions in the distal third of the vagina, 45-50 Gy is delivered to treat the inguinal lymph nodes.
Treatment recommendations for stage II disease
Radiation therapy is the standard treatment for patients with stage II vaginal carcinoma.
Combination radiation therapy with brachytherapy and EBRT is usually employed to deliver a combined dose of 70-80 Gy to the primary tumor volume.
For lesions of the lower third of the vagina, 45-50 Gy is delivered to the pelvic lymph nodes, the inguinal lymph nodes, or both.
The superiority of brachytherapy plus EBRT to brachytherapy alone has been demonstrated in several studies.
Neoadjuvant chemotherapy followed by radical surgery may be an alternative to radiation therapy. In a small prospective study, patients were treated with 3 cycles of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2; 27% of patients achieved a complete response, and all of the remaining patients were able to undergo surgical resection.
Treatment recommendations for stage III disease
Radiation therapy is the standard treatment for patients with stage III vaginal carcinoma.
Generally, patients receive EBRT with 45-50 Gy delivered to the pelvis and a sidewall boost of 60 Gy. Interstitial or intracavitary radiation therapy is then performed so as to yield a total tumor dose of 75-80 Gy.
Intensity-modulated radiation has also been used.
Chemotherapy is often given in conjunction with radiation therapy.
Surgery is rarely suggested for treatment of vulvovaginal cancer,
but some have advocated exenterative procedures
or combination therapies (eg, EBRT with intracavitary radiation and then radical vulvectomy and bilateral inguinofemoral lymph node dissection).
Treatment recommendations for stage IV disease
Radiation therapy is the standard treatment for patients with stage IV vaginal carcinoma.
A typical approach involves a combination of interstitial radiation therapy, intracavitary radiation therapy, and EBRT followed by an interstitial or intracavitary implant for a total tumor dose of 75-80 Gy and a lateral sidewall boost of 55-60 Gy.
Rarely, an exenterative surgical procedure is performed to treat the carcinoma.
Treatment recommendations for recurrent disease
Most recurrences occur within the first 6-12 months.
The prognosis for recurrent vaginal carcinoma is poor, but some patients with central lesions may be eligible for surgical treatment (ie, exenteration) or radiation therapy. There is no standard chemotherapeutic regimen for the treatment of recurrence.
Special considerations
Radiation may be performed for palliation of symptoms.
Limited data are available on the use of concurrent chemotherapy with radiation therapy in vaginal cancer.
However, drugs that are active against cervical cancer have been applied to the treatment of vaginal cancer—for example, cisplatin 50 mg/m2 every 21 days throughout treatment with radiation.
Other regimens used in cervical cancer include the following
:
Cisplatin plus paclitaxel
Carboplatin (alone or with paclitaxel)
Cisplatin plus topotecan
Cisplatin plus gemcitabine
An interstitial implant is important if invasion is deeper than 0.5 cm.