Vaginal cancer

PDQ® Treatment Health Professionals

Important: This information is intended mainly for use by doctors and other health care professionals. If you have questions about this topic, you can ask your doctor, or call the Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

Vaginal cancer

GENERAL INFORMATION
STAGE INFORMATION TNM definitions AJCC stage groupings Stage 0 Stage I Stage II Stage III Stage IVA Stage IVB
TREATMENT OPTION OVERVIEW
STAGE 0 VAGINAL CANCER Squamous cell carcinoma in situ
STAGE I VAGINAL CANCER Squamous cell carcinoma Adenocarcinoma
STAGE II VAGINAL CANCER Squamous cell carcinoma Adenocarcinoma
STAGE III VAGINAL CANCER Squamous cell carcinoma Adenocarcinoma
STAGE IVA VAGINAL CANCER Squamous cell carcinoma Adenocarcinoma
STAGE IVB VAGINAL CANCER Squamous cell carcinoma Adenocarcinoma
RECURRENT VAGINAL CANCER

GENERAL INFORMATION

Carcinomas of the vagina are uncommon tumors comprising 1%-2% of gynecologic malignancies. They can be effectively treated, and when found in early stages, are often curable. The histologic distinction between squamous cell carcinoma and adenocarcinoma is important because the two types represent distinct diseases, each with a different pathogenesis and natural history. Squamous cell vaginal cancer (approximately 85% of cases) initially spreads superficially within the vaginal wall and later invades the paravaginal tissues and the parametria. Distant metastases occur most commonly in the lungs and liver.[1] Adenocarcinoma (approximately 15% of cases) has a peak incidence between 17 and 21 years of age and differs from squamous cell carcinoma by an increase in pulmonary metastases and supraclavicular and pelvic node involvement.[2] Rarely, melanoma and sarcoma are described as primary vaginal cancers. Adenosquamous carcinoma is a rare and aggressive mixed epithelial tumor comprising approximately 1%-2% of cases.

Prognosis depends primarily on the stage of disease, but survival is reduced in patients who are greater than 60 years of age, are symptomatic at the time of diagnosis, have lesions of the middle and lower third of the vagina, or have poorly differentiated tumors.[3,4] In addition, the length of vaginal wall involvement has been found to be significantly correlated to survival and stage of disease in squamous cell carcinoma patients.[5]

Therapeutic alternatives depend on stage; surgery or radiation therapy is highly effective in early stages, while radiation therapy is the primary treatment of more advanced stages.[6,7] Chemotherapy has not been shown to be curative for advanced vaginal cancer, and there are no standard drug regimens.

Clear cell adenocarcinomas are rare and occur most often in patients less than 30 years of age who have a history of in utero exposure to diethylstilbestrol (DES). The incidence of this disease, which is highest for those exposed during the first trimester, peaked in the mid-1970s, reflecting the use of DES in the 1950s.[2] Young women with a history of in utero DES exposure should prospectively be followed carefully in order to diagnose this disease at an early stage. In women who have been carefully followed and well-managed, the disease is highly curable.

Vaginal adenosis is most commonly found in young women who had in utero exposure to DES and may coexist with a clear cell adenocarcinoma, although it rarely progresses to adenocarcinoma. Adenosis is replaced by squamous metaplasia, which occurs naturally, and requires follow-up but not removal. The natural history, prognosis, and treatment of other primary vaginal cancers (sarcoma, melanoma, lymphoma, and carcinoid tumors) may be different, and specific references should be sought.[8]

References:

Gallup DG, Talledo OE, Shah KJ, et al.: Invasive squamous cell carcinoma of the vagina: a 14-year study. Obstetrics and Gynecology 69(5): 782-785, 1987.
Herbst AL, Robboy SJ, Scully RE, et al.: Clear cell adenocarcinoma of the vagina and cervix in girls: analysis of 170 registry cases. American Journal of Obstetrics and Gynecology 119(5): 713-724, 1974.
Kucera H, Vavra N: Radiation management of primary carcinoma of the vagina: clinical and histopathological variables associated with survival. Gynecologic Oncology 40(1): 12-16, 1991.
Eddy GL, Marks RD, Miller MC, et al.: Primary invasive vaginal carcinoma. American Journal of Obstetrics and Gynecology 165(2): 292-298, 1991.
Dixit S, Singhal S, Baboo HA: Squamous cell carcinoma of the vagina: a review of 70 cases. Gynecologic Oncology 48(1): 80-87, 1993.
Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. International Journal of Radiation Oncology, Biology, Physics 15(6): 1283-1290, 1988.
Pride GL, Schultz AE, Chuprevich TW, et al.: Primary invasive squamous carcinoma of the vagina. Obstetrics and Gynecology 53(2): 218-225, 1979.
Sulak P, Barnhill D, Heller P, et al.: Nonsquamous cancer of the vagina. Gynecologic Oncology 29(3): 309-320, 1988.

STAGE INFORMATION

Cervical biopsies are mandatory to rule out carcinoma of the cervix. Carcinoma of the vulva should also be ruled out.

Stages are defined by the Federation Internationale de Gynecologie et d'Obstetrique (FIGO) or the American Joint Committee on Cancer's (AJCC) TNM classification.[1]

TNM definitions

The definitions of the T categories correspond to the several stages accepted by FIGO.

Primary tumor (T)

TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
Tis 0: Carcinoma in situ
T1 I: Tumor confined to vagina
T2 II: Tumor invades paravaginal tissues but not to pelvic wall
T3 III: Tumor extends to pelvic wall
T4* IVA: Tumor invades mucosa of the bladder or rectum and/or extends beyond

the true pelvis (Bullous edema is not sufficient evidence to
classify a tumor as T4.)

*Note: If the bladder mucosa is not involved, the tumor is Stage III.

Regional Lymph Nodes (N)

NX: Regional nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Pelvic or inguinal lymph node metastasis

Distant metastasis (M)

MX: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis

AJCC stage groupings

Stage 0

Tis, N0, M0

Stage I

T1, N0, M0

Stage II

T2, N0, M0

Stage III

T1, N1, M0
T2, N1, M0
T3, N0, M0
T3, N1, M0

Stage IVA

T4, Any N, M0

Stage IVB

Any T, Any N, M1

References:

Vagina. In: American Joint Committee on Cancer: AJCC Cancer Staging Manual. Philadelphia, Pa: Lippincott-Raven Publishers, 5th ed., 1997, pp 185-188.

TREATMENT OPTION OVERVIEW

Factors to be considered in planning therapy for vaginal cancer are stage, size, and location of the lesion; presence or absence of the uterus; and whether there has been prior pelvic irradiation. In a large series of women studied retrospectively over 30 years, 50% had undergone hysterectomy prior to the diagnosis of vaginal cancer.[1] In this post-hysterectomy group, 31 of 50 (62%) developed cancers limited to the upper one third of the vagina. In women who had not previously undergone hysterectomy, upper vaginal lesions were found in only 17 of 50 (34%). The lymphatics may drain to pelvic or inguinal nodes or both, depending on tumor location, and consideration should be given to these areas in treatment planning. The proximity of the vagina to the bladder or rectum limits treatment options and increases complications involving these organs. For carcinoma of the vagina in its early stages, standard treatment applied by gynecologic oncologists or radiation oncologists is highly effective. For patients with stages III and IVA disease, radiation therapy alone is standard. For stage IVB disease, current therapy is inadequate, and no established anticancer drugs can be considered standard treatment. Considering the rarity of such patients, they should be considered candidates for clinical trials using anticancer drugs and/or radiosensitizers to attempt to improve survival or local control.

The designations in PDQ that treatments are "standard" or "under clinical evaluation" are not to be used as a basis for reimbursement determinations.

References:

Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecologic Oncology 56(1): 45-52, 1995.

STAGE 0 VAGINAL CANCER

Squamous cell carcinoma in situ

This disease is usually multifocal and commonly occurs at the vaginal vault. Because vaginal intraepithelial neoplasia (VAIN) is associated with other genital neoplasias, the cervix (when present) and vulva should be carefully examined. The treatments listed below produce equivalent cure rates. The selection of treatment depends on patient factors and local expertise, e.g., anatomical distortion of the vaginal vault (related to wall closure at the time of hysterectomy) requires excision for technical reasons to exclude the possibility of invasion by buried disease. Lesions with hyperkeratosis respond better to excision or laser vaporization than to 5-FU.[1]

Treatment options:

1. Wide local excision with or without skin grafting.

2. Partial or total vaginectomy with skin grafting for multifocal or extensive disease.

3. Intravaginal chemotherapy with 5% fluorouracil cream. Instillation of 1.5 grams weekly for 10 weeks has been found to be as effective as more frequent use.[2]

4. Laser therapy.[2]

5. Intracavitary irradiation delivering 6,000-7,000 cGy to the mucosa.[3,4] The entire vaginal mucosa should be treated.[5]

References:

Wright VC, Chapman W: Intraepithelial neoplasia of the lower female genital tract: etiology, investigation, and management. Seminars in Surgical Oncology 8(4): 180-190, 1992.
Krebs HB: Treatment of vaginal intraepithelial neoplasia with laser and topical 5-fluorouracil. Obstetrics and Gynecology 73(4): 657-660, 1989.
Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. International Journal of Radiation Oncology, Biology, Physics 15(6): 1283-1290, 1988.
Woodman CB, Mould JJ, Jordan JA: Radiotherapy in the management of vaginal intraepithelial neoplasia after hysterectomy. British Journal of Obstetrics and Gynaecology 95(10): 976-979, 1988.
Perez CA, Madoc-Jones H: Carcinoma of the vagina. In: Perez CA, Brady LW, Eds.: Principles and Practice of Radiation Oncology. Philadelphia: JB Lippincott, 1987, pp 1023-1035.

STAGE I VAGINAL CANCER

Squamous cell carcinoma

Treatment options with equivalent effectiveness (choice depends on patient factors and local expertise):

For superficial stage I less than 0.5 centimeters thick:

1. Intracavitary radiation therapy. In most instances, 6,000-7,000 cGy prescribed to 0.5 centimeters is delivered to the tumor over 5-7 days (external-beam irradiation is required for bulky lesions).[1] For lesions of the lower third of the vagina, elective irradiation of 4,500-5,000 cGy is given to pelvic +/- inguinal lymph nodes.[1]

2. Surgery. Wide local excision or total vaginectomy with vaginal reconstruction, especially in lesions of the upper vagina. In cases with close or positive surgical margins, adjuvant radiation therapy should be considered.[2]

For stage I lesions greater than 0.5 centimeters thick:

1. Surgery. In lesions of the upper one-third of the vagina, radical vaginectomy and pelvic lymphadenectomy should be performed. Construction of a neo-vagina may be performed if feasible and if desired by the patient.[2,3] In lesions of the lower one-third, inguinal lymphadenectomy should be performed. In cases with close or positive surgical margins, adjuvant radiation therapy should be considered.[2]

2. Radiation therapy. Combination of interstitial (single-plane implant) and intracavitary therapy to a dose of at least 7,500 cGy to the primary tumor. External-beam irradiation, in addition to brachytherapy, is advocated for poorly differentiated or infiltrating tumors that may have a higher probability of lymph node metastasis.[1,4] For lesions of the lower third of the vagina, elective irradiation of 4,500-5,000 cGy is given to the pelvic +/- inguinal lymph nodes.[1]

Adenocarcinoma

Treatment options:

1. Surgery. Because the tumor spreads subepithelially, total radical vaginectomy and hysterectomy with lymph node dissection are indicated. The deep pelvic nodes are dissected if the lesion invades the upper vagina, and the inguinal nodes are removed if the lesion originates in the lower vagina. Construction of a neo-vagina may be performed if feasible and if desired by the patient.[2] In cases with close or positive surgical margins, adjuvant radiation therapy should be considered.[2,3]

2. Intracavitary and interstitial radiation as previously described for squamous cell cancer.[1] For lesions of the lower third of the vagina, elective irradiation of 4,500-5,000 cGy is given to the pelvic +/- inguinal lymph nodes.[1]

3. Combined local therapy in selected cases, which may include wide local excision, lymph node sampling, and interstitial therapy.[5]

References:

Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. International Journal of Radiation Oncology, Biology, Physics 15(6): 1283-1290, 1988.
Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecologic Oncology 56(1): 45-52, 1995.
Rubin SC, Young J, Mikuta JJ: Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up. Gynecologic Oncology 20: 346-353, 1985.
Andersen ES.: Primary carcinoma of the vagina: a study of 29 cases. Gynecologic Oncology 33(3): 317-320, 1989.
Senekjian EK, Frey KW, Anderson D, et al.: Local therapy in stage I clear cell adenocarcinoma of the vagina. Cancer 60(6): 1319-1324, 1987.

STAGE II VAGINAL CANCER

Squamous cell carcinoma

Treatment options:

Radiation therapy is the standard treatment of stage II vaginal carcinoma.

1. Combination of brachytherapy and external-beam radiation therapy to deliver a combined dose of 7,000-8,000 cGy to the primary tumor volume.[1] For lesions of the lower third of the vagina, elective irradiation of 4,500-5,000 cGy is given to the pelvic +/- inguinal lymph nodes.[1,2]

2. Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy.[3,4]

Adenocarcinoma

Treatment options:

1. Combination of brachytherapy and external-beam radiation therapy to deliver a combined dose of 7,000-8,000 cGy to the primary tumor.[1] For lesions of the lower third of the vagina, elective irradiation of 4,500- 5,000 cGy is given to the pelvic +/- inguinal lymph nodes.[1,2]

2. Radical surgery (radical vaginectomy or pelvic exenteration) with or without radiation therapy.

References:

Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. International Journal of Radiation Oncology, Biology, Physics 15(6): 1283-1290, 1988.
Andersen ES.: Primary carcinoma of the vagina: a study of 29 cases. Gynecologic Oncology 33(3): 317-320, 1989.
Rubin SC, Young J, Mikuta JJ: Squamous carcinoma of the vagina: treatment, complications, and long-term follow-up. Gynecologic Oncology 20: 346-353, 1985.
Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecologic Oncology 56(1): 45-52, 1995.

STAGE III VAGINAL CANCER

Squamous cell carcinoma

Treatment options:

1. Combination of interstitial, intracavitary, and external-beam radiation therapy. External irradiation over a period of 5-6 weeks (including pelvic nodes) followed by an interstitial and/or intracavitary implant for a total tumor dose of 7,500-8,000 cGy and a dose to the lateral pelvic wall of 5,500-6,000 cGy.[1]

2. Rarely, surgery may be combined with the above.[2]

Adenocarcinoma

Treatment options:

1. Combination of interstitial, intracavitary, and external-beam radiation therapy as described for squamous cell cancer.[1]

2. Rarely, surgery may be combined with the above.[2]

References:

Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. International Journal of Radiation Oncology, Biology, Physics 15(6): 1283-1290, 1988.
Boronow RC, Hickman BT, Reagan MT, et al.: Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer: II. Results, complications, and dosimetric and surgical considerations. American Journal of Clinical Oncology 10(2): 171-181, 1987.

STAGE IVA VAGINAL CANCER

Squamous cell carcinoma

Treatment options:

1. Combination of interstitial, intracavitary, and external-beam radiation therapy.[1]

2. Rarely, surgery may be combined with the above.[2]

Adenocarcinoma

Treatment options:

1. Combination of interstitial, intracavitary, and external-beam radiation therapy.[1]

2. Rarely, surgery may be combined with the above.

References:

Perez CA, Camel HM, Galakatos AE, et al.: Definitive irradiation in carcinoma of the vagina: long-term evaluation of results. International Journal of Radiation Oncology, Biology, Physics 15(6): 1283-1290, 1988.
Boronow RC, Hickman BT, Reagan MT, et al.: Combined therapy as an alternative to exenteration for locally advanced vulvovaginal cancer: II. Results, complications, and dosimetric and surgical considerations. American Journal of Clinical Oncology 10(2): 171-181, 1987.

STAGE IVB VAGINAL CANCER

Squamous cell carcinoma

Patients should be considered candidates for one of the ongoing clinical trials to improve therapeutic results. Standard treatment is inadequate. Treatment options:

Radiation (for palliation of symptoms) with or without chemotherapy.

Adenocarcinoma

Patients should be considered candidates for one of the ongoing clinical trials to improve therapeutic results.

Treatment options:

Radiation (for palliation of symptoms) with or without chemotherapy.

RECURRENT VAGINAL CANCER

Recurrence carries a grave prognosis. In a large series only five of fifty patients with recurrence were salvaged by surgery or radiation therapy. All five of these salvaged patients originally presented with stage I or II disease and failed in the central pelvis.[1] Most recurrences are in the first 2 years after treatment. In centrally recurrent vaginal cancers, some patients may be candidates for pelvic exenteration or irradiation. Clinical trials are also appropriate and should be considered. Neither cisplatin nor mitoxantrone has significant activity in recurrent or advanced squamous cell cancer. There is no standard chemotherapy.

References:

Stock RG, Chen AS, Seski J: A 30-year experience in the management of primary carcinoma of the vagina: analysis of prognostic factors and treatment modalities. Gynecologic Oncology 56(1): 45-52, 1995.

Date Last Modified: 02/1999

PDQ® Treatment Health Professionals

Vaginal cancer

Table of Contents