Vulvar Cancer

  • Dana-Farber/Brigham and Women's Cancer Care

    Vulvar cancer refers to cancer of the external female genital organs, including the clitoris, vaginal lips, and the opening to the vagina. Learn about vulvar cancer and find information on how we support and care for women with vulvar cancer before, during, and after treatment.

Treatment 

Whether you’ve been diagnosed with a gynecologic cancer or are at high risk of developing one, the specialists in the Susan F. Smith Center for Women's Cancers Gynecologic Oncology Program provide expert, compassionate care.

Because gynecologic cancers can have a wide range of physical and emotional effects, we’ve assembled a team of experts from many disciplines to help you and your family cope with cancer and its treatment. Our doctors and other caregivers will work closely with you to develop an individualized treatment plan suited to your situation.

As well as providing specialized medical care, we offer a range of supportive services, including nutritional counseling, emotional and spiritual support, financial advice, and complementary therapies such as acupuncture and massage.

As a major research institution, Dana-Farber is able to provide patients not only with outstanding care but also with some of the most advanced therapies available. We base our treatments on the latest scientific findings, and many patients have the opportunity to participate in clinical trials of the potential therapies of the future.

Learn more about our treatment and care for women with gynecologic cancers 

Our clinicians are experts in treating all types of gynecologic cancers, including: 

  • Cervical cancer
  • Carcinosarcomas
  • Endometrial cancer
  • Gestational trophoblastic tumor
  • Ovarian cancer
  • Epithelial ovarian cancer
  • Germ cell ovarian cancer
  • Low malignant ovarian cancer
  • Borderline ovarian cancer
  • Primary peritoneal cancer
  • Fallopian tube cancer
  • Vaginal cancer
  • Vulvar cancer
  • Choriocarcinoma
  • Molar pregnancy

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Information for: Patients | Healthcare Professionals

General Information About Vulvar Cancer

Vulvar cancer is a rare disease in which malignant (cancer) cells form in the tissues of the vulva.

Vulvar cancer forms in a woman's external genitalia. The vulva includes:

  • Inner and outer lips of the vagina.
  • Clitoris (sensitive tissue between the lips).
  • Opening of the vagina and its glands.
  • Mons pubis (the rounded area in front of the pubic bones that becomes covered with hair at puberty).
  • Perineum (the area between the vulva and the anus).
Anatomy of the vulva; drawing shows the mons pubis, clitoris, urethral opening, inner and outer lips of the vagina, and the vaginal opening. Also shown are the perineum and anus.
Anatomy of the vulva. The vulva includes the mons pubis, clitoris, urethral opening, inner and outer lips of the vagina, vaginal opening, and perineum.

Vulvar cancer most often affects the outer vaginal lips. Less often, cancer affects the inner vaginal lips, clitoris, or vaginal glands.

Vulvar cancer usually forms slowly over a number of years. Abnormalcells can grow on the surface of the vulvar skin for a long time. This condition is called vulvar intraepithelial neoplasia (VIN). Because it is possible for VIN to become vulvar cancer, it is very important to get treatment.

Having vulvar intraepithelial neoplasia or HPV infection can affect the risk of vulvar cancer.

Anything that increases your risk of getting a disease is called a risk factor. Having a risk factor does not mean that you will get cancer; not having risk factors doesn't mean that you will not get cancer. Talk with your doctor if you think you may be at risk. Risk factors for vulvar cancer include the following:

  • Having vulvar intraepithelial neoplasia (VIN).
  • Having human papillomavirus (HPV) infection.
  • Having a history of genitalwarts.

Other possible risk factors include the following:

  • Having many sexual partners.
  • Having first sexual intercourse at a young age.
  • Having a history of abnormal Pap tests (Pap smears).

Possible signs of vulvar cancer include bleeding or itching.

Vulvar cancer often does not cause early symptoms. When symptoms occur, they may be caused by vulvar cancer or by other conditions. Check with your doctor if you have any of the following problems:

  • A lump or growth on the vulva.
  • Changes in the vulvar skin, such as color changes or growths that look like a wart or ulcer.
  • Itching in the vulvar area, that does not go away.
  • Bleeding not related to menstruation (periods).
  • Tenderness in the vulvar area.

Tests that examine the vulva are used to detect (find) and diagnose vulvar cancer.

The following tests and procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking the vulva for signs of disease, such as lumps or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
  • Biopsy: The removal of samples of cells or tissues from the vulva so they can be viewed under a microscope by a pathologist to check for signs of cancer.

Certain factors affect prognosis (chance of recovery) and treatment options.

The prognosis (chance of recovery) and treatment options depend on the following:

  • The stage of the cancer.
  • The patient's age and general health.
  • Whether the cancer has just been diagnosed or has recurred (come back).

Stages of Vulvar Cancer

After vulvar cancer has been diagnosed, tests are done to find out if cancer cells have spread within the vulva or to other parts of the body.

The process used to find out if cancer has spread within the vulva or to other parts of the body is called staging. The information gathered from the staging process determines the stage of the disease. It is important to know the stage in order to plan treatment. The following tests and procedures may be used in the staging process:

  • Pelvic exam: An exam of the vagina, cervix, uterus, fallopian tubes, ovaries, and rectum. The doctor or nurse inserts one or two lubricated, gloved fingers of one hand into the vagina and places the other hand over the lower abdomen to feel the size, shape, and position of the uterus and ovaries. A speculum is also inserted into the vagina and the doctor or nurse looks at the vagina and cervix for signs of disease. A Pap test or Pap smear of the cervix is usually done. The doctor or nurse also inserts a lubricated, gloved finger into the rectum to feel for lumps or abnormal areas.
    Pelvic exam; drawing shows a side view of the female reproductive anatomy during a pelvic exam. The uterus, left fallopian tube, left ovary, cervix, vagina, bladder, and rectum are shown. Two gloved fingers of one hand of the doctor or nurse are shown inserted into the vagina, while the other hand is shown pressing on the lower abdomen. The inset shows a woman covered by a drape on an exam table with her legs apart and her feet in stirrups.
    Pelvic exam. A doctor or nurse inserts one or two lubricated, gloved fingers of one hand into the vagina and presses on the lower abdomen with the other hand. This is done to feel the size, shape, and position of the uterus and ovaries. The vagina, cervix, fallopian tubes, and rectum are also checked.
  • Colposcopy: A procedure in which a colposcope (a lighted, magnifying instrument) is used to check the vagina and cervix for abnormal areas. Tissue samples may be taken using a curette (spoon-shaped instrument) and checked under a microscope for signs of disease.
  • Cystoscopy: A procedure to look inside the bladder and urethra to check for abnormal areas. A cystoscope is inserted through the urethra into the bladder. A cystoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.
  • Proctoscopy: A procedure to look inside the rectum and anus to check for abnormal areas. A proctoscope is inserted into the anus and rectum. A proctoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue samples, which are checked under a microscope for signs of cancer.
  • X-rays: An x-ray is a type of energy beam that can go through the body and onto film, making a picture of areas inside the body. To stage vulvar cancer, x-rays may be taken of the organs and bones inside the chest, and the pelvic bones.
  • Intravenous pyelogram (IVP): A series of x-rays of the kidneys, ureters, and bladder to find out if cancer has spread to these organs. A contrast dye is injected into a vein. As the contrast dye moves through the kidneys, ureters and bladder, x-rays are taken to see if there are any blockages. This procedure is also called intravenous urography.
  • CT scan (CAT scan): A procedure that makes a series of detailed pictures of areas inside the body, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
  • MRI (magnetic resonance imaging): A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body. This procedure is also called nuclear magnetic resonance imaging (NMRI).
  • PET scan (positron emission tomography scan): A procedure to find malignanttumorcells in the body. A small amount of radioactiveglucose (sugar) is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
  • Sentinel lymph node biopsy: The removal of the sentinel lymph node during surgery. The sentinel lymph node is the first lymph node to receive lymphatic drainage from a tumor. It is the first lymph node the cancer is likely to spread to from the tumor. A radioactive substance and/or blue dye is injected near the tumor. The substance or dye flows through the lymphducts to the lymph nodes. The first lymph node to receive the substance or dye is removed. A pathologist views the tissue under a microscope to look for cancer cells. If cancer cells are not found, it may not be necessary to remove more lymph nodes. Sentinel lymph node biopsy may be done during surgery to remove the tumor for early-stage vulvar cancer.

There are three ways that cancer spreads in the body.

Cancer can spread through tissue, the lymph system, and the blood:

  • Tissue. The cancer spreads from where it began by growing into nearby areas.
  • Lymph system. The cancer spreads from where it began by getting into the lymph system. The cancer travels through the lymph vessels to other parts of the body.
  • Blood. The cancer spreads from where it began by getting into the blood. The cancer travels through the blood vessels to other parts of the body.

Cancer may spread from where it began to other parts of the body.

When cancer spreads to another part of the body, it is called metastasis. Cancer cells break away from where they began (the primary tumor) and travel through the lymph system or blood.

  • Lymph system. The cancer gets into the lymph system, travels through the lymph vessels, and forms a tumor (metastatic tumor) in another part of the body.
  • Blood. The cancer gets into the blood, travels through the blood vessels, and forms a tumor (metastatic tumor) in another part of the body.

The metastatic tumor is the same type of cancer as the primary tumor. For example, if vulvar cancer spreads to the lung, the cancer cells in the lung are actually vulvar cancer cells. The disease is metastatic vulvar cancer, not lung cancer.

In vulvar intraepithelial neoplasia (VIN), abnormal cells are found on the surface of the vulvar skin.

These abnormalcells are not cancer. Vulvar intraepithelial neoplasia (VIN) may become cancer and spread into nearby tissue. VIN is sometimes called stage 0 or carcinoma in situ.

The following stages are used for vulvar cancer:

Stage I

In stage I, cancer has formed. The tumor is found only in the vulva or perineum (area between the rectum and the vagina). Stage I is divided into stages IA and IB.

Tumor size compared to everyday objects; shows various measurements of a tumor compared to a pea, peanut, walnut, and lime
Pea, peanut, walnut, and lime show tumor sizes.

  • In stage IA, the tumor is 2 centimeters or smaller and has spread 1 millimeter or less into the tissue of the vulva. Cancer has not spread to the lymph nodes.
  • In stage IB, the tumor is larger than 2 centimeters or has spread more than 1 millimeter into the tissue of the vulva. Cancer has not spread to the lymph nodes.
    Millimeters; drawing shows millimeters (mm) using everyday objects. A sharp pencil point shows 1 mm, a new crayon point shows 2 mm, and a new pencil-top eraser shows 5 mm.
    Millimeters (mm). A sharp pencil point is about 1 mm, a new crayon point is about 2 mm, and a new pencil eraser is about 5 mm.

Stage II

In stage II, the tumor is any size and has spread into the lower part of the urethra, the lower part of the vagina, or the anus. Cancer has not spread to the lymph nodes.

Stage III

In stage III, the tumor is any size and may have spread into the lower part of the urethra, the lower part of the vagina, or the anus. Cancer has spread to one or more nearby lymph nodes. Stage III is divided into stages IIIA, IIIB, and IIIC.

  • In stage IIIA, cancer is found in 1 or 2 lymph nodes that are smaller than 5 millimeters or in one lymph node that is 5 millimeters or larger.
  • In stage IIIB, cancer is found in 2 or more lymph nodes that are 5 millimeters or larger, or in 3 or more lymph nodes that are smaller than 5 millimeters.
  • In stage IIIC, cancer is found in lymph nodes and has spread to the outside surface of the lymph nodes.

Stage IV

In stage IV, the tumor has spread into the upper part of the urethra, the upper part of the vagina, or to other parts of the body. Stage IV is divided into stages IVA and IVB.

  • In stage IVA:
    • cancer has spread into the lining of the upper urethra, the upper vagina, the bladder, or the rectum, or has attached to the pelvic bone; or
    • cancer has spread to nearby lymph nodes and the lymph nodes are not moveable or have formed an ulcer.
  • In stage IVB, cancer has spread to lymph nodes in the pelvis or to other parts of the body.

Recurrent Vulvar Cancer

Recurrentvulvar cancer is cancer that has recurred (come back) after it has been treated. The cancer may come back in the vulva or in other parts of the body.

Treatment Option Overview

There are different types of treatment for patients with vulvar cancer.

Different types of treatments are available for patients with vulvar cancer. Some treatments are standard (the currently used treatment), and some are being tested in clinical trials. A treatment clinical trial is a research study meant to help improve current treatments or obtain information on new treatments for patients with cancer. When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial. Some clinical trials are open only to patients who have not started treatment.

Four types of standard treatment are used:

Surgery

Surgery is the most common treatment for vulvar cancer. The goal of surgery is to remove all the cancer without any loss of the woman's sexual function. One of the following types of surgery may be done:

  • Laser surgery: A surgical procedure that uses a laser beam (a narrow beam of intense light) as a knife to make bloodless cuts in tissue or to remove a surface lesion such as a tumor.
  • Wide local excision: A surgical procedure to remove the cancer and some of the normal tissue around the cancer.
  • Radical local excision: A surgical procedure to remove the cancer and a large amount of normal tissue around it. Nearby lymph nodes in the groin may also be removed.
  • Ultrasound surgical aspiration (USA): A surgical procedure to break the tumor up into small pieces using very fine vibrations. The small pieces of tumor are washed away and removed by suction. This procedure causes less damage to nearby tissue.
  • Vulvectomy: A surgical procedure to remove part or all of the vulva:
    • Skinning vulvectomy: The top layer of vulvar skin where the cancer is found is removed. Skin grafts from other parts of the body may be needed to cover the area where the skin was removed.
    • Modified radical vulvectomy: Surgery to remove part of the vulva. Nearby lymph nodes may also be removed.
    • Radical vulvectomy: Surgery to remove the entire vulva. Nearby lymph nodes are also removed.
  • Pelvic exenteration: A surgical procedure to remove the lower colon, rectum, and bladder. The cervix, vagina, ovaries, and nearby lymph nodes are also removed. Artificial openings (stoma) are made for urine and stool to flow from the body into a collection bag.

Even if the doctor removes all the cancer that can be seen at the time of the surgery, some patients may have chemotherapy or radiation therapy after surgery to kill any cancer cells that are left. Treatment given after the surgery, to lower the risk that the cancer will come back, is called adjuvant therapy.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells. There are two types of radiation therapy. External radiation therapy uses a machine outside the body to send radiation toward the cancer. Internal radiation therapy uses a radioactive substance sealed in needles, seeds, wires, or catheters that are placed directly into or near the cancer. The way the radiation therapy is given depends on the type and stage of the cancer being treated.

Chemotherapy

Chemotherapy is a cancer treatment that uses drugs to stop the growth of cancer cells, either by killing the cells or by stopping the cells from dividing. When chemotherapy is taken by mouth or injected into a vein or muscle, the drugs enter the bloodstream and can reach cancer cells throughout the body (systemic chemotherapy). When chemotherapy is placed directly into the cerebrospinal fluid, an organ, a body cavity such as the abdomen, or onto the skin, the drugs mainly affect cancer cells in those areas (regional chemotherapy). The way the chemotherapy is given depends on the type and stage of the cancer being treated.

Topical chemotherapy for vulvar cancer may be applied to the skin in a cream or lotion.

See Drugs Approved to Treat Vulvar Cancer for more information.

Biologic therapy

Biologic therapy is a treatment that uses the patient’s immune system to fight cancer. Substances made by the body or made in a laboratory are used to boost, direct, or restore the body’s natural defenses against cancer. This type of cancer treatment is also called biotherapy or immunotherapy.

Imiquimod is a biologic therapy that may be used to treat vulvar lesions and is applied to the skin in a cream.

New types of treatment are being tested in clinical trials.

Information about clinical trials is available from the NCI Web site.

Patients may want to think about taking part in a clinical trial.

For some patients, taking part in a clinical trial may be the best treatment choice. Clinical trials are part of the cancer research process. Clinical trials are done to find out if new cancer treatments are safe and effective or better than the standard treatment.

Many of today's standard treatments for cancer are based on earlier clinical trials. Patients who take part in a clinical trial may receive the standard treatment or be among the first to receive a new treatment.

Patients who take part in clinical trials also help improve the way cancer will be treated in the future. Even when clinical trials do not lead to effective new treatments, they often answer important questions and help move research forward.

Patients can enter clinical trials before, during, or after starting their cancer treatment.

Some clinical trials only include patients who have not yet received treatment. Other trials test treatments for patients whose cancer has not gotten better. There are also clinical trials that test new ways to stop cancer from recurring (coming back) or reduce the side effects of cancer treatment.

Clinical trials are taking place in many parts of the country. See the Treatment Options section that follows for links to current treatment clinical trials. These have been retrieved from NCI's listing of clinical trials.

Follow-up tests may be needed.

Some of the tests that were done to diagnose the cancer or to find out the stage of the cancer may be repeated. Some tests will be repeated in order to see how well the treatment is working. Decisions about whether to continue, change, or stop treatment may be based on the results of these tests. This is sometimes called re-staging.

Some of the tests will continue to be done from time to time after treatment has ended. The results of these tests can show if your condition has changed or if the cancer has recurred (come back). These tests are sometimes called follow-up tests or check-ups.

It is important to have regular follow-up exams to check for recurrentvulvar cancer.

Treatment Options by Stage

Vulvar Intraepithelial Neoplasia (VIN)

Treatment of vulvar intraepithelial neoplasia (VIN) may include the following:

  • Removal of single lesions or wide local excision.
  • Laser surgery.
  • Ultrasound surgical aspiration.
  • Skinning vulvectomy with or without a skin graft.
  • Biologic therapy with topicalimiquimod.

Stage I Vulvar Cancer

Treatment of stage I vulvar cancer may include the following:

  • Wide local excision for lesions that are less than 1 millimeter deep..
  • Radical local excision and removal of nearby lymph nodes.
  • Radical local excision and sentinel lymph node biopsy. If cancer is found in the sentinel lymph node, nearby lymph nodes are also removed.
  • Radiation therapy for patients who cannot have surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I vulvar cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage II Vulvar Cancer

Treatment of stage II vulvar cancer may include the following:

  • Radical local excision and removal of nearby lymph nodes.
  • Modified radical vulvectomy or radical vulvectomy for large tumors. Nearby lymph nodes may be removed. Radiation therapy may be given after surgery.
  • Radical local excision and sentinel lymph node biopsy. If cancer is found in the sentinel lymph node, nearby lymph nodes are also removed.
  • Radiation therapy for patients who cannot have surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II vulvar cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage III Vulvar Cancer

Treatment of stage III vulvar cancer may include the following:

  • Modified radical vulvectomy or radical vulvectomy. Nearby lymph nodes may be removed.Radiation therapy may be given after surgery.
  • Radiation therapy or chemotherapy and radiation therapy followed by surgery.
  • Radiation therapy with or without chemotherapy for patients who cannot have surgery.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III vulvar cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Stage IV Vulvar Cancer

Treatment of stage IVA vulvar cancer may include the following:

  • Radical vulvectomy and pelvic exenteration.
  • Radical vulvectomy followed by radiation therapy.
  • Radiation therapy or chemotherapy and radiation therapy followed by surgery.
  • Radiation therapy with or without chemotherapy for patients who cannot have surgery.

There is no standard treatment for stage IVB vulvar cancer. Treatment may include a clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IVB vulvar cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

Treatment Options for Recurrent Vulvar Cancer

Treatment of recurrentvulvar cancer may include the following:

  • Wide local excision with or without radiation therapy to treat cancer that has come back in the same area.
  • Radical vulvectomy and pelvic exenteration to treat cancer that has come back in the same area.
  • Chemotherapy and radiation therapy with or without surgery.
  • Radiation therapy followed by surgery or chemotherapy.
  • Radiation therapy as palliative treatment to relieve symptoms and improve quality of life.
  • A clinical trial of a new treatment.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent vulvar cancer. For more specific results, refine the search by using other search features, such as the location of the trial, the type of treatment, or the name of the drug. Talk with your doctor about clinical trials that may be right for you. General information about clinical trials is available from the NCI Web site.

To Learn More About Vulvar Cancer

For more information from the National Cancer Institute about vulvar cancer, see the following:

For general cancer information and other resources from the National Cancer Institute, see the following:


This information is provided by the National Cancer Institute.

This information was last updated on December 2, 2013.


General Information About Vulvar Cancer

Incidence and Mortality

Vulvar cancer accounts for about 5% of cancers of the female genital system in the United States.

Estimated new cases and deaths from vulvar cancer in the United States in 2013:[1]

  • New cases: 4,700.
  • Deaths: 990.

The vulva is the area immediately external to the vagina, including the mons pubis, labia, clitoris, Bartholin glands, and perineum. The labia majora are the most common site of vulvar carcinoma involvement and account for about 50% of cases. The labia minora account for 15% to 20% of vulvar carcinoma cases. The clitoris and Bartholin glands are less frequently involved.[2] Lesions are multifocal in about 5% of cases. About 90% of vulvar carcinomas are squamous cell cancers.[3] This evidence summary covers squamous cell cancers and vulvar intraepithelial neoplasias (VIN), some of which are thought to be precursors to invasive squamous cell cancers.

Prognosis

Survival is dependent on the pathologic status of the inguinal nodes and whether spread to adjacent structures has occurred. The size of the primary tumor is less important in defining prognosis.[4] In patients with operable disease without nodal involvement, the overall survival (OS) rate is 90%; however, in patients with nodal involvement, the 5-year OS rate is approximately 50% to 60%.[5]

Risk Factors

Risk factors for lymph node metastasis include the following:[5][6][7][8][9]

  • Clinical node status.
  • Age.
  • Degree of differentiation.
  • Tumor stage.
  • Tumor thickness.
  • Depth of stromal invasion.
  • Presence of capillary-lymphatic space invasion.

Overall, about 30% of patients with operable disease have lymph nodal spread.

In many cases, the development of vulvar cancer is preceded by condyloma or squamous dysplasia. The prevailing evidence favors human papillomavirus (HPV) as a causative factor in many genital tract carcinomas.[10] The HPV-related basaloid and warty types are associated with VIN. About 75% to 100% of basaloid and warty carcinomas harbor HPV infection. In addition to the much higher prevalence of HPV in these subtypes than in the keratinizing subtypes, the basaloid and warty subtypes also share many common risk factors with cervical cancers, including multiplicity of sex partners, early age at initiation of sexual intercourse, and history of abnormal Pap smears.[11] HPV-associated VIN (termed usual-type VIN when high-grade 2 and 3) is most common in women younger than 50 years, whereas non-HPV VIN (termed differentiated-type VIN when high-grade 3) is most common in older women. The former lesion-type VIN grade 1 is no longer classified as a true VIN.[12][13]

The pattern of spread is influenced by the histology. Well-differentiated lesions tend to spread along the surface with minimal invasion, whereas anaplastic lesions are more likely to be deeply invasive. Spread beyond the vulva is either to adjacent organs such as the vagina, urethra, and anus, or via the lymphatics to the inguinal and femoral lymph nodes, followed by the deep pelvic nodes. Hematogenous spread appears to be uncommon.

References:

  1. American Cancer Society.: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed January 10, 2014.

  2. Macnab JC, Walkinshaw SA, Cordiner JW, et al.: Human papillomavirus in clinically and histologically normal tissue of patients with genital cancer. N Engl J Med 315 (17): 1052-8, 1986.

  3. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

  4. Vulva. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 379-81.

  5. Homesley HD, Bundy BN, Sedlis A, et al.: Assessment of current International Federation of Gynecology and Obstetrics staging of vulvar carcinoma relative to prognostic factors for survival (a Gynecologic Oncology Group study). Am J Obstet Gynecol 164 (4): 997-1003; discussion 1003-4, 1991.

  6. Boyce J, Fruchter RG, Kasambilides E, et al.: Prognostic factors in carcinoma of the vulva. Gynecol Oncol 20 (3): 364-77, 1985.

  7. Sedlis A, Homesley H, Bundy BN, et al.: Positive groin lymph nodes in superficial squamous cell vulvar cancer. A Gynecologic Oncology Group Study. Am J Obstet Gynecol 156 (5): 1159-64, 1987.

  8. Binder SW, Huang I, Fu YS, et al.: Risk factors for the development of lymph node metastasis in vulvar squamous cell carcinoma. Gynecol Oncol 37 (1): 9-16, 1990.

  9. Homesley HD, Bundy BN, Sedlis A, et al.: Prognostic factors for groin node metastasis in squamous cell carcinoma of the vulva (a Gynecologic Oncology Group study) Gynecol Oncol 49 (3): 279-83, 1993.

  10. Hampl M, Sarajuuri H, Wentzensen N, et al.: Effect of human papillomavirus vaccines on vulvar, vaginal, and anal intraepithelial lesions and vulvar cancer. Obstet Gynecol 108 (6): 1361-8, 2006.

  11. Schiffman M, Kjaer SK: Chapter 2: Natural history of anogenital human papillomavirus infection and neoplasia. J Natl Cancer Inst Monogr (31): 14-9, 2003.

  12. Pepas L, Kaushik S, Bryant A, et al.: Medical interventions for high grade vulval intraepithelial neoplasia. Cochrane Database Syst Rev (4): CD007924, 2011.

  13. Sideri M, Jones RW, Wilkinson EJ, et al.: Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med 50 (11): 807-10, 2005.

Cellular Classification of Vulvar Cancer

Presented below is an adaptation of the histologic classification of vulvar disease and precursor lesions of cancer of the vulva developed by the International Society for the Study of Vulvar Disease.[1] This evidence summary deals with vulvar intraepithelial neoplasias (VIN) and invasive carcinomas.

Non-neoplastic epithelial disorders of skin and mucosa

  • Lichen sclerosus (lichen sclerosus et atrophicus).
  • Squamous cell hyperplasia (formerly hyperplastic dystrophy).
  • Other dermatoses.

VIN

  • Usual type (high-grade 2 and 3).
  • Differentiated type (high-grade 3).

Paget disease of the vulva

  • Characteristic large pale cells in the epithelium and skin adnexa.

Other histologies

  • Basal cell carcinoma.
  • Histiocytosis X.
  • Malignant melanoma.
  • Sarcoma.
  • Verrucous carcinoma.

References:

  1. Sideri M, Jones RW, Wilkinson EJ, et al.: Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med 50 (11): 807-10, 2005.

Stage Information for Vulvar Cancer

The diagnosis of vulvar cancer is made by biopsy. The patient may be examined under anesthesia. Cystoscopy, proctoscopy, x-ray examination of the lungs, and intravenous urography (as needed), are used for staging purposes. Suspected bladder or rectal involvement must be confirmed by biopsy. The staging system does not apply to malignant melanoma of the vulva, which is staged like melanoma of the skin.[1]

Definitions: FIGO

The Fédération Internationale de Gynécologie et d’Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define vulvar cancer; the FIGO system is most commonly used.[1][2] Stage is based upon pathology staging at the time of surgery or prior to any radiation or chemotherapy, if they are the initial treatment modalities.[3]

Table 1. Carcinoma of the Vulvaa

Stage I

Tumor confined to the vulva.

IA

Lesions ≤2 cm in size, confined to the vulva or perineum and with stromal invasion ≤1.0 mmb, no nodal metastasis.

IB

Lesions >2 cm in size or with stromal invasion >1.0 mmb, confined to the vulva or perineum, with negative nodes.

Stage II

Tumor of any size with extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with negative nodes.

Stage III

Tumor of any size with or without extension to adjacent perineal structures (1/3 lower urethra, 1/3 lower vagina, anus) with positive inguino-femoral lymph nodes.

IIIA

(i) With 1 lymph node metastasis (≥5 mm), or

(ii) 1–2 lymph node metastasis(es) (<5 mm).

IIIB

(i) With 2 or more lymph node metastases (≥5 mm), or

(ii) 3 or more lymph node metastases (<5 mm).

IIIC

With positive nodes with extracapsular spread.

Stage IV

Tumor invades other regional (2/3 upper urethra, 2/3 upper vagina), or distant structures.

IVA

Tumor invades any of the following:

(i) upper urethral and/or vaginal mucosa, bladder mucosa, rectal mucosa, or fixed to pelvic bone, or

(ii) fixed or ulcerated inguino-femoral lymph nodes.

IVB

Any distant metastasis including pelvic lymph nodes.

aAdapted from FIGO Committee on Gynecologic Oncology.[2]

bThe depth of invasion is defined as the measurement of the tumor from the epithelial-stromal junction of the adjacent most superficial dermal papilla to the deepest point of invasion.

Grade is reported in registry systems. A two-, three-, or four-grade system may be used. If not specified, the following system is generally used:[1]

  • GX: Grade cannot be assessed.
  • G1: Well differentiated.
  • G2: Moderately differentiated.
  • G3: Poorly differentiated.
  • G4: Undifferentiated.

References:

  1. Vulva. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 379-81.

  2. Pecorelli S: Revised FIGO staging for carcinoma of the vulva, cervix, and endometrium. Int J Gynaecol Obstet 105 (2): 103-4, 2009.

  3. Hopkins MP, Reid GC, Johnston CM, et al.: A comparison of staging systems for squamous cell carcinoma of the vulva. Gynecol Oncol 47 (1): 34-7, 1992.

Treatment Option Overview

Standard primary treatment for vulvar cancer is surgery. Radiation is usually added to surgery in patients with stage III or IV disease.[1][2][3] Newer strategies have integrated surgery, radiation therapy, and chemotherapy and tailor the treatment to the extent of clinical and pathologic disease. Patterns of practice in combining these treatments vary.[4]

Since invasive and preinvasive neoplasms of the vulva may be HPV-induced and the carcinogenic effect may be widespread in the vulvar epithelium, patients should be followed regularly for symptoms or signs of recurrence. Because there are few patients with advanced disease (stages III and IV), only limited data are available on treatment efficacy in this setting, and there is no standard chemotherapy regimen for these patients. Physicians should offer eligible patients with stage III or IV disease participation in clinical trials.

Information about ongoing clinical trials is available on the NCI Web site.

Role of Surgery

Primary surgery

Until the 1980s, the standard therapeutic approach to therapy for invasive locoregional vulvar carcinomas was radical surgery, including complete en bloc resection of the vulva and regional lymph nodes. Because of the high attendant complication rates, wound healing problems, lymphedema, and functional deficits, the trend since then has been toward more limited surgery, often combined with radiation therapy.[5] (Refer to the Role of Radiation Therapy section of this summary for more information.)

In tumors clinically confined to the vulva or perineum, radical local excision with a margin of at least 1 cm has generally replaced radical vulvectomy; separate incision has replaced en bloc inguinal node dissection; ipsilateral inguinal node dissection has replaced bilateral dissection for laterally localized tumors; and femoral lymph node dissection has been omitted in many cases. However, the different surgical techniques have not been directly compared in randomized controlled trials. In addition, even the nonrandomized studies suffer from lack of uniform staging definitions and clear descriptions of lymph node dissection or ancillary radiation.[6][Levels of evidence: 3iiiDii, 3iiiDiv] The evidence base is therefore limited.

Nodal surgery

Another strategy to minimize the morbidity incurred by groin-node dissection in patients with early clinical-stage disease is sentinel node dissection, reserving groin dissection for those with metastases to the sentinel node(s).

In a multicenter case series, 403 patients with primary vulvar squamous cell cancers smaller than 4 cm and clinically negative groin nodes underwent 623 sentinel node dissections using radioactive tracer and blue dye for sentinel node identification.[7] All patients had radical resection of the primary tumor. Node metastases were identified in 26% of sentinel node procedures, and these patients went on to full inguinofemoral lymphadenectomy. The patients with negative sentinel nodes were followed with no further therapy.

Local morbidity was much lower in patients who underwent sentinel node dissection than in patients with positive sentinel nodes who also underwent inguinofemoral lymphadenectomy: wound breakdown 11.7% vs. 34.0%; cellulitis 4.5% vs. 21.3%; chronic lymphedema 1.9% vs. 25.2%, respectively (P < .0001 for all comparisons). Mean hospital stay was also shorter: 8.4 vs. 13.7 days (P < .0001). After two local recurrences in 17 patients with multifocal primary tumors, the protocol was amended to only allow patients with unifocal tumors into the study. Actuarial groin recurrence for all patients with negative sentinel node dissections at 2 years was 3% (95% confidence interval [CI], 1%–6%) and 2% (95% CI, 1%–5%) for those with unifocal primary tumors.[7][Level of evidence: 3iiiDiv]

Therefore, sentinel node dissection may be useful when performed by a surgeon experienced in the procedure, and it may avoid the need for full groin node dissection or radiation in patients with clinically nonsuspicious lymph nodes. (Refer to the Role of Radiation Therapy section of this summary for more information.)

Role of Radiation Therapy

Groin lymph node metastases are present in approximately 20% to 35% of patients with tumors clinically confined to the vulva and with clinically negative nodes.[7][8] Lymph node dissection is traditionally part of the primary surgical therapy in all but the smallest tumors. However, a major cause of morbidity after surgery is groin node dissection, which is associated with high rates of wound breakdown, lymphocele formation, and chronic lymphedema. Some investigators recommend radiation therapy as a means to avoid the morbidity of lymph node dissection, but it is not clear whether radiation therapy can achieve the same local control rates or survival rates as lymph node dissection in early stage disease.

Inguinal nodes

A randomized trial to address the radiation therapy issue in patients with clinically localized vulvar cancer has been reported.[8][9] In that study, women with disease clinically confined to the vulva, who did not have groin lymph nodes clinically suspicious for metastases, underwent radical vulvectomy followed by either groin radiation (50 Gy in 2 Gy fractions) or groin dissection (plus groin radiation if nodes were pathologically involved).

Although the planned accrual was 300 patients, the study was stopped after 58 women were randomly assigned to it because of worse outcomes in the radiation therapy arm. Five (18.5%) of 27 women in the radiation therapy arm and 0 of 25 women in the surgery arm had a groin recurrence, but this difference was not statistically significant (relative risk [RR], 10.21; 95% CI, 0.59–175.78). There were ten deaths in the radiation therapy arm versus three deaths in the groin dissection study arm (RR, 4.31; 95% CI, 1.03–18.15). Disease-specific mortality was not statistically significantly different between the two arms; however, there were eight versus two vulvar cancer-related deaths (including one related to groin dissection), in the radiation therapy arm and groin dissection arm, respectively (RR, 3.70; 95% CI, 0.87–15.80).[8][9][Level of evidence 1iiA] There were fewer cases of lymphedema in the radiation therapy arm (0 vs. 7) and shorter hospital stays. The dose penetration of the radiation (3 cm for full dose) has been criticized as inadequate.[8] In summary, the trial was stopped prematurely, and little can be said about the relative efficacy of the two treatment approaches.[8]

Pelvic nodes

Pelvic radiation has been compared to pelvic node dissection in the setting of documented groin node-positive disease. Patients with clinical stage I to stage IV primary squamous cell carcinoma of the vulva in whom groin nodal metastases were found at radical vulvectomy and bilateral groin node dissection were randomly assigned during the surgical procedure to receive either ipsilateral pelvic node resection or pelvic radiation (45 Gy–50 Gy at 1.8 Gy–2.0 Gy per fraction).[10] Because of a perceived emerging benefit of radiation, the planned accrual of 152 was stopped after 114 patients were randomly assigned. However, the apparent benefit of radiation was subsequently attenuated with further follow-up.

After a median follow-up of 74 months, the 6-year overall survival (OS) rate was 51% in the radiation arm versus 41% in the pelvic node dissection arm (hazard ratio [HR], 0.61; 95% CI, 0.3–1.3; P = .18). Vulvar cancer-specific mortality was statistically significantly lower in the radiation study arm: 29% versus 51% in the pelvic node resection arm (HR, 0.49; 95% CI, 0.28–0.87; P = .015) However, there were 14 intercurrent deaths in the radiation therapy arm versus two deaths in the pelvic dissection study arm. Late chronic lymphedema was similar in the radiation therapy and pelvic dissection groups arms (16% vs. 22%), respectively.[10][Level of evidence: 1iiB]

Radical radiation therapy can be used for patients unable to tolerate surgery or deemed unsuitable for surgery because of site or extent of disease.[11][12][13][14]

Role of Chemotherapy

There is no standard chemotherapy for vulvar cancer, and reports describing the use of this modality in the setting of metastatic or recurrent disease are anecdotal.[5] Extrapolating from regimens used for anal or cervical squamous cell cancers, chemotherapy has been studied in combination with radiation in the neoadjuvant setting or as primary therapy in advanced disease. Chemotherapy regimens have included various combinations of 5-fluorouracil (5-FU), cisplatin, mitomycin-C, or bleomycin.[5] There is no clear evidence of improvement in survival or palliation. Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents.

Systemic treatment for inoperable patients

A systematic review of the use of neoadjuvant chemoradiation in patients who were considered inoperable or who would have required extensive surgery, such as pelvic exenteration, colostomy, or urinary diversion revealed no randomized trials.[15] Five nonrandomized studies that met the inclusion criteria of neoadjuvant chemoradiation administered in this population with an intent to permit curative surgery were reviewed.[16][17][18][19][20] The five studies used four different chemoradiation schedules and different radiation therapy dose-fractionation techniques. In the four studies using 5-FU + cisplatin or 5-FU + mitomycin-C, the operability rate after chemoradiation ranged from 63% to 92%.[16][17][18][19]

In the one study using bleomycin, the operability rate was only 20%.[20] In summary, there is evidence that neoadjuvant chemoradiation with 5-FU plus either cisplatin or mitomycin-C may convert patients to more operable status, but the evidence base is limited by study design. In addition to a paucity of randomized trials, interpretation of these studies is complicated by the lack of a standard definition of inoperability.[4][Level of evidence: 3iiiDiv] Treatment-related toxicity is substantial.

Systemic treatment for operable patients

There is also limited evidence regarding the use of neoadjuvant chemoradiation in advanced operable cases of vulvar cancer, but the available data do not suggest an advantage to this approach. A systematic review found only one randomized trial that addressed this issue, and it was published only in abstract form.[4][21] In that trial, 68 patients with advanced vulvar cancer (T2 >4 cm, T3, any case with positive lymph nodes) were randomly assigned to receive preoperative neoadjuvant radiation therapy (50 Gy) concomitantly with 5-FU plus mitomycin-C versus primary surgery. Neoadjuvant therapy-related serious toxicity was high (13 of 24 patients; 10 patients had wound diastasis). After a mean follow-up of 42 months, the 5-year OS rates in the neoadjuvant and primary surgery groups were 30% and 49%, respectively (RR of death, 1.39; 95% CI, 0.94–2.06; P = .19).[4][21][Level of evidence 1iiA]

References:

  1. Hacker NF, Van der Velden J: Conservative management of early vulvar cancer. Cancer 71 (4 Suppl): 1673-7, 1993.

  2. Thomas GM, Dembo AJ, Bryson SC, et al.: Changing concepts in the management of vulvar cancer. Gynecol Oncol 42 (1): 9-21, 1991.

  3. Homesley HD, Bundy BN, Sedlis A, et al.: Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 68 (6): 733-40, 1986.

  4. Shylasree TS, Bryant A, Howells RE: Chemoradiation for advanced primary vulval cancer. Cochrane Database Syst Rev (4): CD003752, 2011.

  5. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

  6. Ansink A, van der Velden J: Surgical interventions for early squamous cell carcinoma of the vulva. Cochrane Database Syst Rev (2): CD002036, 2000.

  7. Van der Zee AG, Oonk MH, De Hullu JA, et al.: Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol 26 (6): 884-9, 2008.

  8. Stehman FB, Bundy BN, Thomas G, et al.: Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys 24 (2): 389-96, 1992.

  9. van der Velden J, Fons G, Lawrie TA: Primary groin irradiation versus primary groin surgery for early vulvar cancer. Cochrane Database Syst Rev (5): CD002224, 2011.

  10. Kunos C, Simpkins F, Gibbons H, et al.: Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial. Obstet Gynecol 114 (3): 537-46, 2009.

  11. Petereit DG, Mehta MP, Buchler DA, et al.: Inguinofemoral radiation of N0,N1 vulvar cancer may be equivalent to lymphadenectomy if proper radiation technique is used. Int J Radiat Oncol Biol Phys 27 (4): 963-7, 1993.

  12. Slevin NJ, Pointon RC: Radical radiotherapy for carcinoma of the vulva. Br J Radiol 62 (734): 145-7, 1989.

  13. Perez CA, Grigsby PW, Galakatos A, et al.: Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy. Cancer 71 (11): 3707-16, 1993.

  14. Kumar PP, Good RR, Scott JC: Techniques for management of vulvar cancer by irradiation alone. Radiat Med 6 (4): 185-91, 1988 Jul-Aug.

  15. van Doorn HC, Ansink A, Verhaar-Langereis M, et al.: Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst Rev 3: CD003752, 2006.

  16. Eifel PJ, Morris M, Burke TW, et al.: Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva. Gynecol Oncol 59 (1): 51-6, 1995.

  17. Landoni F, Maneo A, Zanetta G, et al.: Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma. Gynecol Oncol 61 (3): 321-7, 1996.

  18. Montana GS, Thomas GM, Moore DH, et al.: Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study. Int J Radiat Oncol Biol Phys 48 (4): 1007-13, 2000.

  19. Moore DH, Thomas GM, Montana GS, et al.: Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group. Int J Radiat Oncol Biol Phys 42 (1): 79-85, 1998.

  20. Scheiströen M, Tropé C: Combined bleomycin and irradiation in preoperative treatment of advanced squamous cell carcinoma of the vulva. Acta Oncol 32 (6): 657-61, 1993.

  21. Maneo A, Landoni F, Colombo A, et al.: Randomised study between neoadjuvant chemoradiotherapy and primary surgery for the treatment of advanced vulvar cancer. [Abstract] Int J Gynecol Cancer 13 (Suppl 1): A-PL19, 6, 2003.

Stage 0 Vulvar Cancer

Traditionally, there were three grades of vulvar intraepithelial neoplasia (VIN). However, there is little evidence that all three grades are part of the same biologic continuum or that Grade 1 is even a cancer precursor. In 2004, the International Society for the Study of Vulvar Disease changed its terminology, reserving the designation VIN for two categories of lesions based on morphologic appearance:[1]

  1. Usual-type VIN: Human papillomavirus (HPV)-associated Grades 2 and 3 of warty, basaloid, or mixed histology, and usually occurring in young women.
  2. Differentiated-type VIN: non-HPV-associated Grade 3, and usually occurring in older women.

The term VIN 1 was eliminated.[1] Disease that was previously called VIN 1 (grade I) is generally observed without definitive treatment.

High-grade VIN is usually managed with active therapy because of a higher risk for progression to invasive disease.[2] Estimates of progression rates are imprecise. A systematic literature review that included 88 untreated patients with VIN 3 reported a 9% progression rate (8 of 88 patients) to invasive vulvar cancer during 12 to 96 months of observation. In the same review, the spontaneous regression rate was 1.2%, all of which occurred in women younger than 35 years.[3] However, in a single-center study, 10 of 63 (16%) untreated women with VIN 2 or VIN 3 progressed to invasive cancer after a mean of 3.9 years.[4]

VIN lesions may be multifocal or confluent and extensive. It is important to perform multiple biopsies in treatment planning to exclude occult invasive disease. VIN located in nonhairy areas can be considered an epithelial disease; however, VIN occupying hairy sites usually involves the pilosebaceous apparatus and requires a greater depth of destruction or excision because it can track along hair roots.

Surgical Interventions

The principal treatment approach is surgical, but there is no consensus on the optimal surgical procedure. The goal is to remove or destroy the entire VIN lesion while preserving vulvar anatomy and function. Simple vulvectomy yields a 5-year survival rate of essentially 100% but is seldom indicated. Other more-limited surgical procedures, including separate excision of multiple lesions, are less deforming.[5] The choice of treatment depends on the extent of the disease and the preference or experience of the treating physician. There are no reliable data comparing the efficacy and safety of the various surgical approaches.

A systematic literature review identified only a single randomized trial comparing any of the surgical approaches.[2] In that trial, 30 women with high-grade VIN were randomly assigned to receive carbon dioxide (CO2) laser ablation versus ultrasound surgical aspiration (USA).[6] There were no statistically significant differences in disease recurrence, painful dysuria or burning, adhesions, or eschar formation between the two treatments after 1 year of follow-up. Scarring was observed in 5 of 16 women treated with laser ablation and 0 of14 women treated with USA (P < .01), but consequences of the scarring on sexual function or quality of life were not reported.[6][Level of evidence 1iiDii] The trial was too small to draw reliable conclusions about the relative efficacy of these surgical techniques. The remainder of the surgical literature is derived from case series and is prone to important study biases.[Level of evidence 3iiiD]

Whatever procedure is used, patients are at substantial risk of recurrence, particularly when the lesions are high grade or multifocal.[7] The most common sites of recurrence are the perianal skin, presacral area, and clitoral hood. About 4% of patients treated for VIN subsequently develop invasive cancer.[8][9]

Nonsurgical Interventions

Because of the physical and psychosexual morbidity associated with many vulvar surgical procedures, nonsurgical approaches have been studied. Some of these approaches, including topical 5-fluorouracil, gamma-interferon, bleomycin, and trinitrochlorobenzene, have been largely abandoned because of intolerable local side effects, such as pain, irritation, and ulceration, or high recurrence rates.[10][11] Photodynamic therapy, using topically applied 5-aminolevulinic acid as the sensitizing agent for 635 nm laser light, has also been studied. However, data are limited to small case series with variable response rates.[12][13][Level of evidence: 3iiiDiv]

More recently, among women with high-grade VIN, substantial response rates and acceptable tolerability were reported for topical imiquimod 5%, an immune-response modifier with activity in HPV 6/11-associated vulvar condylomata. Three randomized placebo-controlled trials (including a total of 104 patients) with clinical response as their primary endpoints.[Level of evidence: 1iDiv] have been reported in either peer-reviewed-journal or abstract format.[14][15][16][17] The results of these trials were summarized in a systematic review.[11] At 5 to 6 months, the complete and partial response rates in patients were 36 of 62 and 18 of 62 in the combined imiquimod arms versus 0 of 42 and 1 of 42 in the combined placebo arms (relative risk [RR], 11.95; 95% confidence interval [CI], 3.21–44.51).

In the only trial reporting progression to cancer (at 12 months), there was no difference in progression rate, but the trial was severely underpowered because only 3 of the total 52 women included developed invasive disease by 12 months.[16] The only trial reporting quality of life [16] showed no difference between imiquimod and placebo. Local side effects of imiquimod included pain, edema, erythema, and a single case of erosion. However, no patients had to discontinue treatment as a result of toxicity.

Standard treatment options:

  1. Separate excision of focal lesions.[3]
  2. Wide local excision.[3]
  3. CO2 laser surgery and vaporization.[2][6] A disadvantage of vaporization is that it does not provide tissue for histologic examination to confirm complete removal of the lesion and the absence of invasive disease.
  4. Ultrasonic surgical aspiration (USA).[2][6]
  5. Superficial skinning vulvectomy with or without grafting.[3]
  6. Topical imiquimod for patients wishing to avoid surgery.[11][14][15][16][17]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage 0 vulvar cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Sideri M, Jones RW, Wilkinson EJ, et al.: Squamous vulvar intraepithelial neoplasia: 2004 modified terminology, ISSVD Vulvar Oncology Subcommittee. J Reprod Med 50 (11): 807-10, 2005.

  2. Kaushik S, Pepas L, Nordin A, et al.: Surgical interventions for high grade vulval intraepithelial neoplasia. Cochrane Database Syst Rev (1): CD007928, 2011.

  3. van Seters M, van Beurden M, de Craen AJ: Is the assumed natural history of vulvar intraepithelial neoplasia III based on enough evidence? A systematic review of 3322 published patients. Gynecol Oncol 97 (2): 645-51, 2005.

  4. Jones RW, Rowan DM, Stewart AW: Vulvar intraepithelial neoplasia: aspects of the natural history and outcome in 405 women. Obstet Gynecol 106 (6): 1319-26, 2005.

  5. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

  6. von Gruenigen VE, Gibbons HE, Gibbins K, et al.: Surgical treatments for vulvar and vaginal dysplasia: a randomized controlled trial. Obstet Gynecol 109 (4): 942-7, 2007.

  7. Küppers V, Stiller M, Somville T, et al.: Risk factors for recurrent VIN. Role of multifocality and grade of disease. J Reprod Med 42 (3): 140-4, 1997.

  8. Buscema J, Woodruff JD, Parmley TH, et al.: Carcinoma in situ of the vulva. Obstet Gynecol 55 (2): 225-30, 1980.

  9. Jones RW, Rowan DM: Vulvar intraepithelial neoplasia III: a clinical study of the outcome in 113 cases with relation to the later development of invasive vulvar carcinoma. Obstet Gynecol 84 (5): 741-5, 1994.

  10. Sillman FH, Sedlis A, Boyce JG: A review of lower genital intraepithelial neoplasia and the use of topical 5-fluorouracil. Obstet Gynecol Surv 40 (4): 190-220, 1985.

  11. Pepas L, Kaushik S, Bryant A, et al.: Medical interventions for high grade vulval intraepithelial neoplasia. Cochrane Database Syst Rev (4): CD007924, 2011.

  12. Hillemanns P, Untch M, Dannecker C, et al.: Photodynamic therapy of vulvar intraepithelial neoplasia using 5-aminolevulinic acid. Int J Cancer 85 (5): 649-53, 2000.

  13. Fehr MK, Hornung R, Schwarz VA, et al.: Photodynamic therapy of vulvar intraepithelial neoplasia III using topically applied 5-aminolevulinic acid. Gynecol Oncol 80 (1): 62-6, 2001.

  14. Sterling JC, Smith NA, Loo WJ, et al.: Randomized, doubleblind, placebo-controlled trial for treatment of high grade vulval intraepithelial neoplasia with imiquimod. [Abstract] J Eur Acad Derm Venereol 19 (Suppl 2): A-FC06.1, 22, 2005.

  15. Mathiesen O, Buus SK, Cramers M: Topical imiquimod can reverse vulvar intraepithelial neoplasia: a randomised, double-blinded study. Gynecol Oncol 107 (2): 219-22, 2007.

  16. van Seters M, van Beurden M, ten Kate FJ, et al.: Treatment of vulvar intraepithelial neoplasia with topical imiquimod. N Engl J Med 358 (14): 1465-73, 2008.

  17. Terlou A, van Seters M, Ewing PC, et al.: Treatment of vulvar intraepithelial neoplasia with topical imiquimod: seven years median follow-up of a randomized clinical trial. Gynecol Oncol 121 (1): 157-62, 2011.

Stage I Vulvar Cancer

(Refer to the Treatment Option Overview section of this summary for a more detailed discussion of the roles of surgery, lymph node dissection, and radiation therapy.)

Standard treatment options:

  1. A wide (1 cm margin) excision (without lymph node dissection) for microinvasive lesions (<1 mm invasion) with no associated severe vulvar dystrophy. For all other stage I lesions, if well lateralized, without diffuse severe dystrophy, and with clinically negative nodes, a radical local excision with complete unilateral lymphadenectomy.[1] Candidates for this procedure should have lesions 2 cm or smaller in diameter with 5 mm or less invasion, no capillary lymphatic space invasion, and clinically uninvolved nodes.[2][3]
  2. Radical local excision with ipsilateral or bilateral inguinal and femoral node dissection. In tumor clinically confined to the vulva or perineum, radical local excision with a margin of at least 1 cm has generally replaced radical vulvectomy; separate incision has replaced en bloc inguinal node dissection, ipsilateral inguinal node dissection has replaced bilateral dissection for laterally localized tumors; and femoral lymph node dissection has been omitted in many cases.[4][5][6][7]
  3. Radical local excision and sentinel node dissection, reserving groin dissection for those with metastasis to the sentinel node(s).[8]
  4. Some investigators recommend radical excision and groin nodal radiation therapy as a means to avoid the morbidity of lymph node dissection. However, it is not clear whether radiation therapy can achieve the same local control rates or survival rates as lymph node dissection in early-stage disease. A randomized trial to address this issue in patients with clinically localized vulvar disease was stopped early as a result of early emergence of worse outcomes in the radiation therapy arm.[9][10] (Refer to the Role of Radiation Therapy section of this summary for more information.)
  5. Radical radiation therapy for patients unable to tolerate surgery or deemed unsuitable for surgery because of site or extent of disease.[11][12][13][14]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage I vulvar cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Malfetano JH, Piver MS, Tsukada Y, et al.: Univariate and multivariate analyses of 5-year survival, recurrence, and inguinal node metastases in stage I and II vulvar carcinoma. J Surg Oncol 30 (2): 124-31, 1985.

  2. Stehman FB, Bundy BN, Dvoretsky PM, et al.: Early stage I carcinoma of the vulva treated with ipsilateral superficial inguinal lymphadenectomy and modified radical hemivulvectomy: a prospective study of the Gynecologic Oncology Group. Obstet Gynecol 79 (4): 490-7, 1992.

  3. Hacker NF, Van der Velden J: Conservative management of early vulvar cancer. Cancer 71 (4 Suppl): 1673-7, 1993.

  4. Hoffman MS, Roberts WS, Lapolla JP, et al.: Recent modifications in the treatment of invasive squamous cell carcinoma of the vulva. Obstet Gynecol Surv 44 (4): 227-33, 1989.

  5. Thomas GM, Dembo AJ, Bryson SC, et al.: Changing concepts in the management of vulvar cancer. Gynecol Oncol 42 (1): 9-21, 1991.

  6. Heaps JM, Fu YS, Montz FJ, et al.: Surgical-pathologic variables predictive of local recurrence in squamous cell carcinoma of the vulva. Gynecol Oncol 38 (3): 309-14, 1990.

  7. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

  8. Van der Zee AG, Oonk MH, De Hullu JA, et al.: Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol 26 (6): 884-9, 2008.

  9. Stehman FB, Bundy BN, Thomas G, et al.: Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys 24 (2): 389-96, 1992.

  10. van der Velden J, Fons G, Lawrie TA: Primary groin irradiation versus primary groin surgery for early vulvar cancer. Cochrane Database Syst Rev (5): CD002224, 2011.

  11. Petereit DG, Mehta MP, Buchler DA, et al.: Inguinofemoral radiation of N0,N1 vulvar cancer may be equivalent to lymphadenectomy if proper radiation technique is used. Int J Radiat Oncol Biol Phys 27 (4): 963-7, 1993.

  12. Slevin NJ, Pointon RC: Radical radiotherapy for carcinoma of the vulva. Br J Radiol 62 (734): 145-7, 1989.

  13. Perez CA, Grigsby PW, Galakatos A, et al.: Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy. Cancer 71 (11): 3707-16, 1993.

  14. Kumar PP, Good RR, Scott JC: Techniques for management of vulvar cancer by irradiation alone. Radiat Med 6 (4): 185-91, 1988 Jul-Aug.

Stage II Vulvar Cancer

(Refer to the Treatment Option Overview section of this summary for a more detailed discussion of the roles of surgery, node dissection, and radiation therapy.)

Standard treatment options:

  1. Radical local excision with bilateral inguinal node and femoral node dissection with a resection margin of at least 1 cm.[1] Radical local excision with a margin of at least 1 cm has generally replaced radical vulvectomy, and separate incision has replaced en bloc inguinal node dissection.[2] Large T2 tumors may require modified radical or radical vulvectomy.[3] Adjuvant local radiation therapy may be indicated for surgical margins smaller than 8 mm, capillary-lymphatic space invasion, and thickness greater than 5 mm.[4][5]
  2. Radical excision and sentinel node dissection, reserving groin dissection for those with metastasis to the sentinel node(s).[6]
  3. Some investigators recommend radical excision and groin nodal radiation therapy as a means to avoid the morbidity of lymph node dissection. However, radiation therapy may not achieve the same local control rates or survival rates as lymph node dissection in early-stage disease. A randomized trial to address this issue in patients with clinically localized vulvar disease was stopped early as a result of early emergence of worse outcomes in the radiation therapy group.[7][8] (Refer to the Role of Radiation Therapy section in this summary for more information.)
  4. For those few patients unable to tolerate radical surgery or deemed unsuitable for surgery because of site or extent of disease, radical radiation therapy may be associated with favorable survival.[9][10][11][12]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage II vulvar cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Hacker NF, Van der Velden J: Conservative management of early vulvar cancer. Cancer 71 (4 Suppl): 1673-7, 1993.

  2. Hoffman MS, Roberts WS, Lapolla JP, et al.: Recent modifications in the treatment of invasive squamous cell carcinoma of the vulva. Obstet Gynecol Surv 44 (4): 227-33, 1989.

  3. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

  4. Thomas GM, Dembo AJ, Bryson SC, et al.: Changing concepts in the management of vulvar cancer. Gynecol Oncol 42 (1): 9-21, 1991.

  5. Faul CM, Mirmow D, Huang Q, et al.: Adjuvant radiation for vulvar carcinoma: improved local control. Int J Radiat Oncol Biol Phys 38 (2): 381-9, 1997.

  6. Van der Zee AG, Oonk MH, De Hullu JA, et al.: Sentinel node dissection is safe in the treatment of early-stage vulvar cancer. J Clin Oncol 26 (6): 884-9, 2008.

  7. Stehman FB, Bundy BN, Thomas G, et al.: Groin dissection versus groin radiation in carcinoma of the vulva: a Gynecologic Oncology Group study. Int J Radiat Oncol Biol Phys 24 (2): 389-96, 1992.

  8. van der Velden J, Fons G, Lawrie TA: Primary groin irradiation versus primary groin surgery for early vulvar cancer. Cochrane Database Syst Rev (5): CD002224, 2011.

  9. Petereit DG, Mehta MP, Buchler DA, et al.: Inguinofemoral radiation of N0,N1 vulvar cancer may be equivalent to lymphadenectomy if proper radiation technique is used. Int J Radiat Oncol Biol Phys 27 (4): 963-7, 1993.

  10. Slevin NJ, Pointon RC: Radical radiotherapy for carcinoma of the vulva. Br J Radiol 62 (734): 145-7, 1989.

  11. Perez CA, Grigsby PW, Galakatos A, et al.: Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy. Cancer 71 (11): 3707-16, 1993.

  12. Kumar PP, Good RR, Scott JC: Techniques for management of vulvar cancer by irradiation alone. Radiat Med 6 (4): 185-91, 1988 Jul-Aug.

Stage III Vulvar Cancer

(Refer to the Treatment Option Overview section of this summary for a more detailed discussion of the roles of surgery, node dissection, radiation therapy, and chemotherapy.)

Modified radical or radical vulvectomy with inguinal and femoral lymphadenectomy is the standard therapy.[1] Nodal involvement is a key determinant of survival.

Standard treatment options:

  1. Modified radical or radical vulvectomy with inguinal and femoral node dissection. Radiation therapy to the pelvis and groin is given if inguinal nodes are positive.[2]
  2. Radical vulvectomy with inguinal and femoral node dissection followed by radiation therapy in patients with large primary lesions and narrow margins. Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when there is capillary-lymphatic space invasion and a thickness of greater than 5 mm, particularly if the nodes are involved.[1] Radiation therapy to the pelvis and groin is usually given if two or more groin nodes are involved.[2][3]
  3. Preoperative neoadjuvant radiation therapy or chemoradiation may be used to improve operability and even decrease the extent of surgery required.[4][5][6][7][8][9][10]
  4. For the few patients unable to tolerate radical surgery or deemed unsuitable for surgery because of site or extent of disease, radical radiation therapy may be associated with long-term survival.[11][12] Some physicians prefer to add concurrent 5-FU or 5-FU and cisplatin.[1][13]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III vulvar cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Thomas GM, Dembo AJ, Bryson SC, et al.: Changing concepts in the management of vulvar cancer. Gynecol Oncol 42 (1): 9-21, 1991.

  2. Kunos C, Simpkins F, Gibbons H, et al.: Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial. Obstet Gynecol 114 (3): 537-46, 2009.

  3. Homesley HD, Bundy BN, Sedlis A, et al.: Prognostic factors for groin node metastasis in squamous cell carcinoma of the vulva (a Gynecologic Oncology Group study) Gynecol Oncol 49 (3): 279-83, 1993.

  4. 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. Am J Clin Oncol 10 (2): 171-81, 1987.

  5. Anderson JM, Cassady JR, Shimm DS, et al.: Vulvar carcinoma. Int J Radiat Oncol Biol Phys 32 (5): 1351-7, 1995.

  6. van Doorn HC, Ansink A, Verhaar-Langereis M, et al.: Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst Rev 3: CD003752, 2006.

  7. Eifel PJ, Morris M, Burke TW, et al.: Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva. Gynecol Oncol 59 (1): 51-6, 1995.

  8. Landoni F, Maneo A, Zanetta G, et al.: Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma. Gynecol Oncol 61 (3): 321-7, 1996.

  9. Montana GS, Thomas GM, Moore DH, et al.: Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study. Int J Radiat Oncol Biol Phys 48 (4): 1007-13, 2000.

  10. Moore DH, Thomas GM, Montana GS, et al.: Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group. Int J Radiat Oncol Biol Phys 42 (1): 79-85, 1998.

  11. Perez CA, Grigsby PW, Galakatos A, et al.: Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy. Cancer 71 (11): 3707-16, 1993.

  12. Slevin NJ, Pointon RC: Radical radiotherapy for carcinoma of the vulva. Br J Radiol 62 (734): 145-7, 1989.

  13. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

Stage IV Vulvar Cancer

(Refer to the Treatment Option Overview section of this summary for a more detailed discussion of the roles of surgery, node dissection, radiation therapy, and chemotherapy.)

Stage IVA

Standard treatment options:

  1. Radical vulvectomy and pelvic exenteration.
  2. Surgery followed by radiation therapy for large resected lesions with narrow margins. Localized adjuvant radiation therapy consisting of 45 Gy to 50 Gy may also be indicated when there is capillary-lymphatic space invasion and thickness greater than 5 mm.[1] Radiation therapy to the pelvis and groin is given if two or more groin nodes are involved.[2][3]
  3. Neoadjuvant radiation therapy or chemoradiation of large primary lesions to improve operability, followed by radical surgery.[4][5][6][7][8][9][10]
  4. For those patients unable to tolerate radical vulvectomy or who are deemed unsuitable for surgery because of site or extent of disease, radical radiation therapy may be associated with long-term survival.[11][12] When radiation therapy is used for primary definitive treatment of vulvar cancer, some physicians prefer to add concurrent 5-FU or 5-FU and cisplatin.[1][13][14][15][16][17]

Stage IVB

There is no standard treatment approach in the management of metastatic vulvar cancer. Local therapy must be individualized depending on the extent of local and metastatic disease. There is no standard chemotherapy for metastatic disease, and reports describing the use of this modality are anecdotal.[17] However, by largely extrapolating from regimens used for anal or cervical cancer, chemotherapy has been studied. Regimens have included various combinations of 5-fluorouracil, cisplatin, mitomycin-C, or bleomycin.[6][17][18] Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents. Physicians should offer eligible patients participation in clinical trials.

Information about ongoing clinical trials is available from the NCI Web site

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IVA vulvar cancer and stage IVB vulvar cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Thomas GM, Dembo AJ, Bryson SC, et al.: Changing concepts in the management of vulvar cancer. Gynecol Oncol 42 (1): 9-21, 1991.

  2. Homesley HD, Bundy BN, Sedlis A, et al.: Radiation therapy versus pelvic node resection for carcinoma of the vulva with positive groin nodes. Obstet Gynecol 68 (6): 733-40, 1986.

  3. Kunos C, Simpkins F, Gibbons H, et al.: Radiation therapy compared with pelvic node resection for node-positive vulvar cancer: a randomized controlled trial. Obstet Gynecol 114 (3): 537-46, 2009.

  4. 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. Am J Clin Oncol 10 (2): 171-81, 1987.

  5. Anderson JM, Cassady JR, Shimm DS, et al.: Vulvar carcinoma. Int J Radiat Oncol Biol Phys 32 (5): 1351-7, 1995.

  6. van Doorn HC, Ansink A, Verhaar-Langereis M, et al.: Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst Rev 3: CD003752, 2006.

  7. Eifel PJ, Morris M, Burke TW, et al.: Prolonged continuous infusion cisplatin and 5-fluorouracil with radiation for locally advanced carcinoma of the vulva. Gynecol Oncol 59 (1): 51-6, 1995.

  8. Landoni F, Maneo A, Zanetta G, et al.: Concurrent preoperative chemotherapy with 5-fluorouracil and mitomycin C and radiotherapy (FUMIR) followed by limited surgery in locally advanced and recurrent vulvar carcinoma. Gynecol Oncol 61 (3): 321-7, 1996.

  9. Montana GS, Thomas GM, Moore DH, et al.: Preoperative chemo-radiation for carcinoma of the vulva with N2/N3 nodes: a gynecologic oncology group study. Int J Radiat Oncol Biol Phys 48 (4): 1007-13, 2000.

  10. Moore DH, Thomas GM, Montana GS, et al.: Preoperative chemoradiation for advanced vulvar cancer: a phase II study of the Gynecologic Oncology Group. Int J Radiat Oncol Biol Phys 42 (1): 79-85, 1998.

  11. Slevin NJ, Pointon RC: Radical radiotherapy for carcinoma of the vulva. Br J Radiol 62 (734): 145-7, 1989.

  12. Perez CA, Grigsby PW, Galakatos A, et al.: Radiation therapy in management of carcinoma of the vulva with emphasis on conservation therapy. Cancer 71 (11): 3707-16, 1993.

  13. Russell AH, Mesic JB, Scudder SA, et al.: Synchronous radiation and cytotoxic chemotherapy for locally advanced or recurrent squamous cancer of the vulva. Gynecol Oncol 47 (1): 14-20, 1992.

  14. Berek JS, Heaps JM, Fu YS, et al.: Concurrent cisplatin and 5-fluorouracil chemotherapy and radiation therapy for advanced-stage squamous carcinoma of the vulva. Gynecol Oncol 42 (3): 197-201, 1991.

  15. Koh WJ, Wallace HJ 3rd, Greer BE, et al.: Combined radiotherapy and chemotherapy in the management of local-regionally advanced vulvar cancer. Int J Radiat Oncol Biol Phys 26 (5): 809-16, 1993.

  16. Thomas G, Dembo A, DePetrillo A, et al.: Concurrent radiation and chemotherapy in vulvar carcinoma. Gynecol Oncol 34 (3): 263-7, 1989.

  17. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

  18. Cormio G, Loizzi V, Gissi F, et al.: Cisplatin and vinorelbine chemotherapy in recurrent vulvar carcinoma. Oncology 77 (5): 281-4, 2009.

Recurrent Vulvar Cancer

Treatment and outcome depend on the site and extent of recurrence.[1] Radical excision of localized recurrence may be considered if technically feasible.[2] Palliative radiation therapy is used for some patients. Radiation therapy with or without chemotherapy may be associated with substantial disease-free periods in some patients with a small local recurrence.[3][4][5] When local recurrence occurs more than 2 years after primary treatment, a combination of radiation therapy and surgery may result in a 5-year survival rate of greater than 50%.[6][7]

There is no standard treatment approach in the management of metastatic vulvar cancer. There is no standard chemotherapy, and reports describing the use of this modality are anecdotal.[8] However, by largely extrapolating from regimens used for anal or cervical cancer, chemotherapy has been used, but with no clear evidence of improvement in survival or palliation. Regimens have included various combinations of 5-fluorouracil, cisplatin, mitomycin-C, or bleomycin.[8][9] Given the advanced age and comorbidity of many patients with advanced or recurrent vulvar cancer, patient tolerance is a major consideration in the use of these agents. Physicians should offer eligible patients participation in clinical trials.

Information about ongoing clinical trials is available from the NCI Web site.

Standard treatment options:

  1. Wide local excision with or without radiation in those patients with local recurrence.
  2. Radical vulvectomy and pelvic exenteration in patients with local recurrence.
  3. Synchronous radiation and cytotoxic chemotherapy with or without surgery.[4]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent vulvar cancer. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.

General information about clinical trials is also available from the NCI Web site.

References:

  1. Piura B, Masotina A, Murdoch J, et al.: Recurrent squamous cell carcinoma of the vulva: a study of 73 cases. Gynecol Oncol 48 (2): 189-95, 1993.

  2. Hopkins MP, Reid GC, Morley GW: The surgical management of recurrent squamous cell carcinoma of the vulva. Obstet Gynecol 75 (6): 1001-5, 1990.

  3. Miyazawa K, Nori D, Hilaris BS, et al.: Role of radiation therapy in the treatment of advanced vulvar carcinoma. J Reprod Med 28 (8): 539-41, 1983.

  4. Russell AH, Mesic JB, Scudder SA, et al.: Synchronous radiation and cytotoxic chemotherapy for locally advanced or recurrent squamous cancer of the vulva. Gynecol Oncol 47 (1): 14-20, 1992.

  5. Thomas G, Dembo A, DePetrillo A, et al.: Concurrent radiation and chemotherapy in vulvar carcinoma. Gynecol Oncol 34 (3): 263-7, 1989.

  6. Podratz KC, Symmonds RE, Taylor WF, et al.: Carcinoma of the vulva: analysis of treatment and survival. Obstet Gynecol 61 (1): 63-74, 1983.

  7. Shimm DS, Fuller AF, Orlow EL, et al.: Prognostic variables in the treatment of squamous cell carcinoma of the vulva. Gynecol Oncol 24 (3): 343-58, 1986.

  8. Eifel PJ, Berek JS, Markman MA: Cancer of the cervix, vagina, and vulva. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 1311-44.

  9. van Doorn HC, Ansink A, Verhaar-Langereis M, et al.: Neoadjuvant chemoradiation for advanced primary vulvar cancer. Cochrane Database Syst Rev 3: CD003752, 2006.


This information is provided by the National Cancer Institute.

This information was last updated on February 21, 2013.

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