Cervical Cancer Treatment (PDQ®)


Information for: Patients | Healthcare Professionals

General Information About Cervical Cancer

Cervical cancer is a disease in which malignant (cancer) cells form in the tissues of the cervix.

The cervix is the lower, narrow end of the uterus (the hollow, pear-shaped organ where a fetus grows). The cervix leads from the uterus to the vagina (birth canal).

Anatomy of the female reproductive system; drawing shows the uterus, myometrium (muscular outer layer of the uterus), endometrium (inner lining of the uterus), ovaries, fallopian tubes, cervix, and vagina. 
Anatomy of the female reproductive system. The organs in the female reproductive system include the uterus, ovaries, fallopian tubes, cervix, and vagina. The uterus has a muscular outer layer called the myometrium and an inner lining called the endometrium.

Cervical cancer usually develops slowly over time. Before cancer appears in the cervix, the cells of the cervix go through changes known as dysplasia, in which cells that are not normal begin to appear in the cervicaltissue. Later, cancer cells start to grow and spread more deeply into the cervix and to surrounding areas.

Cervical cancer in children is rare. For more information, see the PDQ summary on Unusual Cancers of Childhood.

Human papillomavirus (HPV) infection is the major risk factor for cervical 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.

Infection of the cervix with human papillomavirus (HPV) is almost always the cause of cervical cancer. Not all women with HPV infection, however, will develop cervical cancer. Women who do not regularly have tests to detect HPV or abnormal cells in the cervix are at increased risk of cervical cancer.

Other possible risk factors include the following:

  • Giving birth to many children.
  • Having many sexual partners.
  • Having first sexual intercourse at a young age.
  • Smoking cigarettes.
  • Using oral contraceptives ("the Pill").
  • Having a weakened immune system.

There are usually no noticeable signs or symptoms of early cervical cancer but it can be detected early with regular check-ups.

Early cervical cancer may not cause noticeable signs or symptoms. Women should have regular check-ups, including tests to check for HPV or abnormal cells in the cervix. The prognosis (chance of recovery) is better when the cancer is found early.

Signs and symptoms of cervical cancer include vaginal bleeding and pelvic pain.

These and other signs and symptoms may be caused by cervical cancer or by other conditions. Check with your doctor if you have any of the following:

  • Vaginal bleeding.
  • Unusual vaginal discharge.
  • Pelvic pain.
  • Pain during sexual intercourse.

Tests that examine the cervix are used to detect (find) and diagnose cervical cancer.

The following procedures may be used:

  • Physical exam and history: An exam of the body to check general signs of health, including checking 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.
  • 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 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.
  • Pap test: A procedure to collect cells from the surface of the cervix and vagina. A piece of cotton, a brush, or a small wooden stick is used to gently scrape cells from the cervix and vagina. The cells are viewed under a microscope to find out if they are abnormal. This procedure is also called a Pap smear.
    Pap test; drawing shows a side view of the female reproductive anatomy during a Pap test. A speculum is shown widening the opening of the vagina. A brush is shown inserted into the open vagina and touching the cervix at the base of the uterus. The rectum is also shown. One inset shows the brush touching the center of the cervix. A second inset shows a woman covered by a drape on an exam table with her legs apart and her feet in stirrups.  
    Pap test. A speculum is inserted into the vagina to widen it. Then, a brush is inserted into the vagina to collect cells from the cervix. The cells are checked under a microscope for signs of disease.
  • Human papillomavirus (HPV) test: A laboratory test used to check DNA or RNA for certain types of HPV infection. Cells are collected from the cervix and DNA or RNA from the cells is checked to find out if an infection is caused by a type of human papillomavirus that is linked to cervical cancer. This test may be done using the sample of cells removed during a Pap test. This test may also be done if the results of a Pap test show certain abnormal cervical cells.
  • Endocervical curettage: A procedure to collect cells or tissue from the cervical canal using a curette (spoon-shaped instrument). Tissue samples may be taken and checked under a microscope for signs of cancer. This procedure is sometimes done at the same time as a colposcopy.
  • 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.
  • Biopsy: If abnormal cells are found in a Pap test, the doctor may do a biopsy. A sample of tissue is cut from the cervix and viewed under a microscope by a pathologist to check for signs of cancer. A biopsy that removes only a small amount of tissue is usually done in the doctor’s office. A woman may need to go to a hospital for a cervical cone biopsy (removal of a larger, cone-shaped sample of cervical tissue).

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

The prognosis (chance of recovery) depends on the following:

  • The patient's age and general health.
  • Whether or not the patient has a certain type of human papillomavirus.
  • The stage of the cancer (whether it affects part of the cervix, involves the whole cervix, or has spread to the lymph nodes or other places in the body).
  • The type of cervical cancer.
  • The size of the tumor.

Treatment options depend on the following:

  • The stage of the cancer.
  • The size of the tumor.
  • The patient's desire to have children.
  • The patient’s age.

Treatment of cervical cancer during pregnancy depends on the stage of the cancer and the stage of the pregnancy. For cervical cancer found early or for cancer found during the last trimester of pregnancy, treatment may be delayed until after the baby is born.

Stages of Cervical Cancer

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

The process used to find out if cancer has spread within the cervix 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:

  • 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.
  • 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.
  • Ultrasound exam: A procedure in which high-energy sound waves (ultrasound) are bounced off internal tissues or organs and make echoes. The echoes form a picture of body tissues called a sonogram.
  • Chest x-ray: An x-ray of the organs and bones inside the chest. 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.
  • 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.
  • Laparoscopy: A surgical procedure to look at the organs inside the abdomen to check for signs of disease. Small incisions (cuts) are made in the wall of the abdomen and a laparoscope (a thin, lighted tube) is inserted into one of the incisions. Other instruments may be inserted through the same or other incisions to perform procedures such as removing organs or taking tissue samples to be checked under a microscope for signs of disease.
  • Pretreatment surgical staging: Surgery (an operation) is done to find out if the cancer has spread within the cervix or to other parts of the body. In some cases, the cervical cancer can be removed at the same time. Pretreatment surgical staging is usually done only as part of a clinical trial.

The results of these tests are viewed together with the results of the original tumor biopsy to determine the cervical cancer stage.

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 cervical cancer spreads to the lung, the cancer cells in the lung are actually cervical cancer cells. The disease is metastatic cervical cancer, not lung cancer.

The following stages are used for cervical cancer:

Carcinoma in Situ (Stage 0)

In carcinoma in situ (stage 0), abnormalcells are found in the innermost lining of the cervix. These abnormal cells may become cancer and spread into nearby normal tissue.

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 I

In stage I, cancer is found in the cervix only. Stage I is divided into stages IA and IB, based on the amount of cancer that is found.

  • Stage IA:
    Stage IA1 and IA2 cervical cancer; drawing shows a cross-section of the cervix and vagina. An inset shows cancer in the cervix that is up to 5 mm deep, but not more than 7 mm wide. 
    Stage IA1 and IA2 cervical cancer. A very small amount of cancer that can only be seen with a microscope is found in the tissues of the cervix. In stage IA1, the cancer is not more than 3 millimeters deep and not more than 7 millimeters wide. In stage IA2, the cancer is more than 3 but not more than 5 millimeters deep, and not more than 7 millimeters wide.
    A very small amount of cancer that can only be seen with a microscope is found in the tissues of the cervix. Stage IA is divided into stages IA1 and IA2, based on the size of the tumor.
    • In stage IA1, the cancer is not more than 3 millimeters deep and not more than 7 millimeters wide.
    • In stage IA2, the cancer is more than 3 but not more than 5 millimeters deep, and not more than 7 millimeters wide.
     
  • Stage IB is divided into stages IB1 and IB2.
    Stage IB1 and IB2 cervical cancer shown in three cross-section drawings of the cervix and vagina. An inset on the left shows stage IB1 cancer that is 7 mm wide and more than 5 mm deep. Drawing in the middle shows stage IB1 cancer that is smaller than 4 cm. Drawing on the right shows stage IB2 cancer that is larger than 4 cm. 
    Stage IB1 and IB2 cervical cancer. In stage IB1, the cancer can only be seen with a microscopic and is more than 5 mm deep or more than 7 mm wide OR the cancer can be seen without a microscope and is 4 cm or smaller. In stage IB2, the cancer is larger than 4 cm.
    • In stage IB1:
      • the cancer can only be seen with a microscope and is more than 5 millimeters deep and more than 7 millimeters wide; or
      • the cancer can be seen without a microscope and is 4 centimeters or smaller.
       
    • In stage IB2, the cancer can be seen without a microscope and is larger than 4 centimeters.
     

Stage II

Stage II cervical cancer; drawing shows a cross-section of the uterus, cervix and vagina. In stages IIA1 and IIA2, cancer that is 4 cm is shown in the cervix and in the upper third of the vagina. In stage IIB, cancer is shown in the cervix, the upper two thirds of the vagina, and in the tissues around the uterus. 
Stage II cervical cancer. Cancer has spread beyond the cervix but not to the pelvic wall or to the lower third of the vagina. In stages IIA1 and IIA2, cancer has spread beyond the cervix to the vagina. In stage IIA1, the tumor can be seen without a microscope and is 4 centimeters or smaller. In stage IIA2, the tumor can be seen without a microscope and is larger than 4 centimeters. In stage IIB, cancer has spread beyond the cervix to the tissues around the uterus.

In stage II, cancer has spread beyond the cervix but not to the pelvic wall (the tissues that line the part of the body between the hips) or to the lower third of the vagina. Stage II is divided into stages IIA and IIB, based on how far the cancer has spread.

  • Stage IIA: Cancer has spread beyond the cervix to the upper two thirds of the vagina but not to tissues around the uterus. Stage IIA is divided into stages IIA1 and IIA2, based on the size of the tumor.
    • In stage IIA1, the tumor can be seen without a microscope and is 4 centimeters or smaller.
    • In stage IIA2, the tumor can be seen without a microscope and is larger than 4 centimeters.
     
  • Stage IIB: Cancer has spread beyond the cervix to the tissues around the uterus.

Stage III

In stage III, cancer has spread to the lower third of the vagina, and/or to the pelvic wall, and/or has caused kidney problems. Stage III is divided into stages IIIA and IIIB, based on how far the cancer has spread.

  • Stage IIIA:
    Stage IIIA cervical cancer; drawing shows a cross-section of the cervix and vagina. Cancer is shown in the cervix and in the full length of the vagina. 
    Stage IIIA cervical cancer. Cancer has spread to the lower third of the vagina but not to the pelvic wall.
    Cancer has spread to the lower third of the vagina but not to the pelvic wall.
  • Stage IIIB:
    Stage IIIB cervical cancer; drawing shows cancer in the cervix, the vagina, and  the pelvic wall, blocking the ureter on the right. The uterus and kidneys are also shown. 
    Stage IIIB cervical cancer. Cancer has spread to the pelvic wall; and/or the tumor has become large enough to block the ureters (the tubes that connect the kidneys to the bladder). The drawing shows the ureter on the right blocked by the cancer. This blockage can cause the kidney to enlarge or stop working.
    • Cancer has spread to the pelvic wall; and/or
    • the tumor has become large enough to block the ureters (the tubes that connect the kidneys to the bladder). This blockage can cause the kidneys to enlarge or stop working.
     

Stage IV

In stage IV, cancer has spread to the bladder, rectum, or other parts of the body. Stage IV is divided into stages IVA and IVB, based on where the cancer is found.

  • Stage IVA:
    Stage IVA cervical cancer; drawing and inset show that cancer has spread from the cervix to the bladder and rectal wall. 
    Stage IVA cervical cancer. Cancer has spread to nearby organs, such as the bladder or rectum.
    Cancer has spread to nearby organs, such as the bladder or rectum.
  • Stage IVB:
    Stage IVB cervical cancer; drawing shows the places in the body where stage IV cervical cancer may spread, including the lymph nodes, lung, liver, intestinal tract, cervix, abdominal wall, and bone. Also shown is an inset of cancer that has spread to a lymph node and through the blood to other parts of the body. 
    Stage IVB cervical cancer. Cancer has spread to parts of the body away from the cervix, such as the liver, intestines, lungs, or bones.
    Cancer has spread to other parts of the body, such as the liver, lungs, bones, or distant lymph nodes.

Recurrent Cervical Cancer

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

Treatment Option Overview

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

Different types of treatment are available for patients with cervical 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.

Three types of standard treatment are used:

Surgery

Surgery (removing the cancer in an operation) is sometimes used to treat cervical cancer. The following surgical procedures may be used:

  • Conization: A procedure to remove a cone-shaped piece of tissue from the cervix and cervical canal. A pathologist views the tissue under a microscope to look for cancer cells. Conization may be used to diagnose or treat a cervical condition. This procedure is also called a cone biopsy.
  • Total hysterectomy: Surgery to remove the uterus, including the cervix. If the uterus and cervix are taken out through the vagina, the operation is called a vaginal hysterectomy. If the uterus and cervix are taken out through a large incision (cut) in the abdomen, the operation is called a total abdominal hysterectomy. If the uterus and cervix are taken out through a small incision in the abdomen using a laparoscope, the operation is called a total laparoscopic hysterectomy.
    Hysterectomy; drawing shows the female reproductive anatomy, including the ovaries, uterus, vagina, fallopian tubes, and cervix. Dotted lines show which organs and tissues are removed in a total hysterectomy, a total hysterectomy with salpingo-oophorectomy, and a radical hysterectomy. An inset shows the location of two possible incisions on the abdomen: a low transverse incision is just above the pubic area and a vertical incision is between the navel and the pubic area. 
    Hysterectomy. The uterus is surgically removed with or without other organs or tissues. In a total hysterectomy, the uterus and cervix are removed. In a total hysterectomy with salpingo-oophorectomy, (a) the uterus plus one (unilateral) ovary and fallopian tube are removed; or (b) the uterus plus both (bilateral) ovaries and fallopian tubes are removed. In a radical hysterectomy, the uterus, cervix, both ovaries, both fallopian tubes, and nearby tissue are removed. These procedures are done using a low transverse incision or a vertical incision.
  • Radical hysterectomy: Surgery to remove the uterus, cervix, part of the vagina, and a wide area of ligaments and tissues around these organs. The ovaries, fallopian tubes, or nearby lymph nodes may also be removed.
  • Modified radical hysterectomy: Surgery to remove the uterus, cervix, upper part of the vagina, and ligaments and tissues that closely surround these organs. Nearby lymph nodes may also be removed. In this type of surgery, not as many tissues and/or organs are removed as in a radical hysterectomy.
  • Bilateral salpingo-oophorectomy: Surgery to remove both ovaries and both fallopian tubes.
  • Pelvic exenteration: Surgery to remove the lower colon, rectum, and bladder. In women, 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 to a collection bag. Plastic surgery may be needed to make an artificial vagina after this operation.
  • Cryosurgery: A treatment that uses an instrument to freeze and destroy abnormal tissue, such as carcinoma in situ. This type of treatment is also called cryotherapy.
  • 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.
  • Loop electrosurgical excision procedure (LEEP): A treatment that uses electrical current passed through a thin wire loop as a knife to remove abnormal tissue or cancer.

Radiation therapy

Radiation therapy is a cancer treatment that uses high-energy x-rays or other types of radiation to kill cancer cells or keep them from growing. There are two types of radiation therapy. External radiationtherapy 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 them 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, or a body cavity such as the abdomen, 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.

See Drugs Approved to Treat Cervical Cancer for more information.

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.

Treatment Options by Stage

Carcinoma in Situ (Stage 0)

Treatment of carcinoma in situ (stage 0) may include the following:

  • Loop electrosurgical excision procedure (LEEP).
  • Laser surgery.
  • Conization.
  • Cryosurgery.
  • Total hysterectomy for women who cannot or no longer want to have children.
  • Internal radiation therapy for women 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 0 cervical 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 IA Cervical Cancer

Treatment of stage IA cervical cancer may include the following:

  • Total hysterectomy with or without bilateral salpingo-oophorectomy.
  • Conization.
  • Modified radical hysterectomy and removal of lymph nodes.
  • Internal radiationtherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IA cervical 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 IB Cervical Cancer

Treatment of stage IB cervical cancer may include the following:

  • A combination of internal radiation therapy and external radiation therapy.
  • Radical hysterectomy and removal of lymph nodes.
  • Radical hysterectomy and removal of lymph nodes followed by radiation therapy plus chemotherapy.
  • Radiation therapy plus chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IB cervical 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 IIA Cervical Cancer

Treatment of stage IIA cervical cancer may include the following:

  • A combination of internal radiation therapy and external radiation therapy plus chemotherapy.
  • Radical hysterectomy and removal of lymph nodes.
  • Radical hysterectomy and removal of lymph nodes followed by radiation therapy plus chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIA cervical 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 IIB Cervical Cancer

Treatment of stage IIB cervical cancer may include internal and external radiation therapy combined with chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIB cervical 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 Cervical Cancer

Treatment of stage III cervical cancer may include internal and external radiation therapy combined with chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage III cervical 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 IVA Cervical Cancer

Treatment of stage IVA cervical cancer may include internal and external radiation therapy combined with chemotherapy.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IVA cervical 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 IVB Cervical Cancer

Treatment of stage IVB cervical cancer may include the following:

  • Radiation therapy as palliative therapy to relieve symptoms caused by the cancer and improve quality of life.
  • Chemotherapy.
  • Clinical trials of new anticancer drugs or drug combinations.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IVB cervical 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 Cervical Cancer

Treatment of recurrentcervical cancer may include the following:

  • Pelvic exenteration followed by radiation therapy combined with chemotherapy.
  • Chemotherapy as palliative therapy to relieve symptoms caused by the cancer and improve quality of life.
  • Clinical trials of new anticancer drugs or drug combinations.

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with recurrent cervical 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 Cervical Cancer

For more information from the National Cancer Institute about cervical 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 November 21, 2013.


General Information About Cervical Cancer

Incidence and Mortality

Estimated new cases and deaths from cervical (uterine cervix) cancer in the United States in 2013:[1]

  • New cases: 12,340.
  • Deaths: 4,030.

Prognostic Factors

The prognosis for patients with cervical cancer is markedly affected by the extent of disease at the time of diagnosis. A vast majority (>90%) of these cases can and should be detected early through the use of the Pap test and human papillomavirus (HPV) testing; however,[2] the current death rate is far higher than it should be, which reflects that, even today, the Pap test and HPV testing are not done on approximately 33% of eligible women. Clinical stage, however, as a prognostic factor must be supplemented by several gross and microscopic pathologic findings in surgically treated patients. These include: volume and grade of tumor, histologic type, lymphatic spread, and vascular invasion.

In a large, surgicopathologic staging study of patients with clinical stage IB disease reported by the Gynecologic Oncology Group (GOG) (GOG-49), the factors that predicted most prominently for lymph node metastases and a decrease in disease-free survival were capillary-lymphatic space involvement by tumor, increasing tumor size, and increasing depth of stromal invasion, with the latter being most important and reproducible.[3][4] In a study of 1,028 patients treated with radical surgery, survival rates correlated more consistently with tumor volume (as determined by precise volumetry of the tumor) than clinical or histologic stage.[5]

A multivariate analysis of prognostic variables in 626 patients with locally advanced disease (primarily stages II, III, and IV) studied by the GOG identified several variables that were significant for progression-free interval and survival:[6]

  • Periaortic and pelvic lymph node status.
  • Tumor size.
  • Patient age.
  • Performance status.
  • Bilateral disease.
  • Clinical stage.

The study confirmed the overriding importance of positive periaortic nodes and suggested further evaluation of these nodes in locally advanced cervical cancer. The status of the pelvic nodes was important only if the periaortic nodes were negative. This was also true for tumor size.

In a large series of cervical cancer patients treated by radiation therapy, the incidence of distant metastases (most frequently to lung, abdominal cavity, liver, and gastrointestinal tract) was shown to increase as the stage of disease increased, from 3% in stage IA to 75% in stage IVA.[7] A multivariate analysis of factors influencing the incidence of distant metastases showed stage, endometrial extension of tumor, and pelvic tumor control to be significant indicators of distant dissemination.[7]

GOG studies have indicated that prognostic factors vary whether clinical or surgical staging are utilized, and with treatment. Delay in radiation delivery completion is associated with poorer progression-free survival when clinical staging is used. It is unclear whether stage, tumor grade, race, and age hold up as prognostic factors in studies utilizing chemoradiation.[8]

Invasive Carcinomas of the Uterine Cervix

Whether adenocarcinoma of the cervix carries a significantly worse prognosis than squamous cell carcinoma of the cervix remains controversial.[9] Reports conflict about the effect of adenosquamous cell type on outcome.[10][11] One report showed that approximately 25% of apparent squamous tumors have demonstrable mucin production and behave more aggressively than their pure squamous counterparts, suggesting that any adenomatous differentiation may confer a negative prognosis.[12] The decreased survival is mainly the result of more advanced stage and nodal involvement rather than cell type as an independent variable. Women with human immunodeficiency virus have more aggressive and advanced disease and a poorer prognosis.[13] A study of patients with known invasive squamous carcinoma of the cervix found that overexpression of the C-myc oncogene was associated with a poorer prognosis.[14] The number of cells in S phase may also have prognostic significance in early cervical carcinoma.[15] HPV type 18 DNA has been found to be an independent adverse molecular prognostic factor. Two studies have shown a worse outcome when identified in cervical cancers of patients undergoing radical hysterectomy and pelvic lymphadenectomy.[16][17]

Human Papillomavirus Infection and Cervical Cancer

Molecular techniques for the identification of HPV DNA are highly sensitive and specific. More than 6 million women in the United States are estimated to have HPV infection, and proper interpretation of these data is important. Epidemiologic studies convincingly demonstrate that the major risk factor for development of preinvasive or invasive carcinoma of the cervix is HPV infection, which far outweighs other known risk factors such as high parity, increasing number of sexual partners, young age at first intercourse, low socioeconomic status, and positive smoking history.[18][19] Some patients with HPV infection appear to be at minimal increased risk for development of cervical preinvasive and invasive malignancies, while others appear to be at significant risk and are candidates for intensive screening programs and/or early intervention.

HPV DNA tests are unlikely to separate patients with low-grade squamous intraepithelial lesions into those who do and those who do not need further evaluation. A study of 642 women found that 83% had one or more tumorigenic HPV types when cervical cytologic specimens were assayed by a sensitive (hybrid capture) technique.[20] The authors of the study and of an accompanying editorial concluded that using HPV DNA testing in this setting does not add sufficient information to justify its cost.[20] HPV DNA testing has proven useful in triaging patients with atypical squamous cells of undetermined significance to colposcopy and has been integrated into current screening guidelines.[20][21][22] Patients with an abnormal cytology of a high-risk type (Bethesda classification) should be thoroughly evaluated with colposcopy and biopsy.

Other studies show patients with low-risk cytology and high-risk HPV infection with types 16, 18, and 31 are more likely to have cervical intraepithelial neoplasia (CIN) or microinvasive histopathology on biopsy.[19][23][24][25] One method has also shown that integration of HPV types 16 and 18 into the genome, leading to transcription of viral and cellular messages, may predict patients who are at greater risk for high-grade dysplasia and invasive cancer.[26] Studies suggest that acute infection with HPV types 16 and 18 conferred an 11- to 16.9-fold risk of rapid development of high-grade CIN,[19][27] but there are conflicting data requiring further evaluation before any recommendations may be made. Patients with low-risk cytology and low-risk HPV types have not been followed long enough to ascertain their risk. At present, studies are ongoing to determine how HPV typing can be used to help stratify women into follow-up and treatment groups. HPV typing may prove useful, particularly in patients with low-grade cytology or cytology of unclear abnormality. At present, how therapy and follow-up should be altered with low- versus high-risk HPV type has not been established.

Related Summaries

Other PDQ summaries containing information related to cervical cancer include the following:

  • Cervical Cancer Prevention
  • Cervical Cancer Screening
  • Unusual Cancers of Childhood (childhood cancer of the cervix)

References:

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

  2. The 1988 Bethesda System for reporting cervical/vaginal cytological diagnoses. National Cancer Institute Workshop. JAMA 262 (7): 931-4, 1989.

  3. Delgado G, Bundy B, Zaino R, et al.: Prospective surgical-pathological study of disease-free interval in patients with stage IB squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. Gynecol Oncol 38 (3): 352-7, 1990.

  4. Zaino RJ, Ward S, Delgado G, et al.: Histopathologic predictors of the behavior of surgically treated stage IB squamous cell carcinoma of the cervix. A Gynecologic Oncology Group study. Cancer 69 (7): 1750-8, 1992.

  5. Burghardt E, Baltzer J, Tulusan AH, et al.: Results of surgical treatment of 1028 cervical cancers studied with volumetry. Cancer 70 (3): 648-55, 1992.

  6. Stehman FB, Bundy BN, DiSaia PJ, et al.: Carcinoma of the cervix treated with radiation therapy. I. A multi-variate analysis of prognostic variables in the Gynecologic Oncology Group. Cancer 67 (11): 2776-85, 1991.

  7. Fagundes H, Perez CA, Grigsby PW, et al.: Distant metastases after irradiation alone in carcinoma of the uterine cervix. Int J Radiat Oncol Biol Phys 24 (2): 197-204, 1992.

  8. Monk BJ, Tian C, Rose PG, et al.: Which clinical/pathologic factors matter in the era of chemoradiation as treatment for locally advanced cervical carcinoma? Analysis of two Gynecologic Oncology Group (GOG) trials. Gynecol Oncol 105 (2): 427-33, 2007.

  9. Steren A, Nguyen HN, Averette HE, et al.: Radical hysterectomy for stage IB adenocarcinoma of the cervix: the University of Miami experience. Gynecol Oncol 48 (3): 355-9, 1993.

  10. Gallup DG, Harper RH, Stock RJ: Poor prognosis in patients with adenosquamous cell carcinoma of the cervix. Obstet Gynecol 65 (3): 416-22, 1985.

  11. Yazigi R, Sandstad J, Munoz AK, et al.: Adenosquamous carcinoma of the cervix: prognosis in stage IB. Obstet Gynecol 75 (6): 1012-5, 1990.

  12. Bethwaite P, Yeong ML, Holloway L, et al.: The prognosis of adenosquamous carcinomas of the uterine cervix. Br J Obstet Gynaecol 99 (9): 745-50, 1992.

  13. Maiman M, Fruchter RG, Guy L, et al.: Human immunodeficiency virus infection and invasive cervical carcinoma. Cancer 71 (2): 402-6, 1993.

  14. Bourhis J, Le MG, Barrois M, et al.: Prognostic value of c-myc proto-oncogene overexpression in early invasive carcinoma of the cervix. J Clin Oncol 8 (11): 1789-96, 1990.

  15. Strang P, Eklund G, Stendahl U, et al.: S-phase rate as a predictor of early recurrences in carcinoma of the uterine cervix. Anticancer Res 7 (4B): 807-10, 1987 Jul-Aug.

  16. Burger RA, Monk BJ, Kurosaki T, et al.: Human papillomavirus type 18: association with poor prognosis in early stage cervical cancer. J Natl Cancer Inst 88 (19): 1361-8, 1996.

  17. Lai CH, Chang CJ, Huang HJ, et al.: Role of human papillomavirus genotype in prognosis of early-stage cervical cancer undergoing primary surgery. J Clin Oncol 25 (24): 3628-34, 2007.

  18. Schiffman MH, Bauer HM, Hoover RN, et al.: Epidemiologic evidence showing that human papillomavirus infection causes most cervical intraepithelial neoplasia. J Natl Cancer Inst 85 (12): 958-64, 1993.

  19. Brisson J, Morin C, Fortier M, et al.: Risk factors for cervical intraepithelial neoplasia: differences between low- and high-grade lesions. Am J Epidemiol 140 (8): 700-10, 1994.

  20. Human papillomavirus testing for triage of women with cytologic evidence of low-grade squamous intraepithelial lesions: baseline data from a randomized trial. The Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesions Triage Study (ALTS) Group. J Natl Cancer Inst 92 (5): 397-402, 2000.

  21. Wright TC Jr, Massad LS, Dunton CJ, et al.: 2006 consensus guidelines for the management of women with abnormal cervical cancer screening tests. Am J Obstet Gynecol 197 (4): 346-55, 2007.

  22. Wright TC Jr, Massad LS, Dunton CJ, et al.: 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 197 (4): 340-5, 2007.

  23. Tabbara S, Saleh AD, Andersen WA, et al.: The Bethesda classification for squamous intraepithelial lesions: histologic, cytologic, and viral correlates. Obstet Gynecol 79 (3): 338-46, 1992.

  24. Cuzick J, Terry G, Ho L, et al.: Human papillomavirus type 16 in cervical smears as predictor of high-grade cervical intraepithelial neoplasia [corrected] Lancet 339 (8799): 959-60, 1992.

  25. Richart RM, Wright TC Jr: Controversies in the management of low-grade cervical intraepithelial neoplasia. Cancer 71 (4 Suppl): 1413-21, 1993.

  26. Klaes R, Woerner SM, Ridder R, et al.: Detection of high-risk cervical intraepithelial neoplasia and cervical cancer by amplification of transcripts derived from integrated papillomavirus oncogenes. Cancer Res 59 (24): 6132-6, 1999.

  27. Koutsky LA, Holmes KK, Critchlow CW, et al.: A cohort study of the risk of cervical intraepithelial neoplasia grade 2 or 3 in relation to papillomavirus infection. N Engl J Med 327 (18): 1272-8, 1992.

Cellular Classification of Cervical Cancer

Squamous cell (epidermoid) carcinoma comprises approximately 90%, and adenocarcinoma comprises approximately 10% of cervical cancers. Adenosquamous and small cell carcinomas are relatively rare. Primary sarcomas of the cervix have been described occasionally, and malignant lymphomas of the cervix, primary and secondary, have also been reported.

Stage Information for Cervical Cancer

Cervical carcinoma has its origins at the squamous-columnar junction whether in the endocervical canal or on the portion of the cervix. The precursor lesion is dysplasia or carcinoma in situ (cervical intraepithelial neoplasia [CIN]), which can subsequently become invasive cancer. This process can be quite slow. Longitudinal studies have shown that in untreated patients with in situ cervical cancer, 30% to 70% will develop invasive carcinoma over a period of 10 to 12 years. However, in about 10% of patients, lesions can progress from in situ to invasive in a period of less than 1 year. As it becomes invasive, the tumor breaks through the basement membrane and invades the cervical stroma. Extension of the tumor in the cervix may ultimately manifest as ulceration, exophytic tumor, or extensive infiltration of underlying tissue including bladder or rectum.

In addition to local invasion, carcinoma of the cervix can spread via the regional lymphatics or bloodstream. Tumor dissemination is generally a function of the extent and invasiveness of the local lesion. While cancer of the cervix generally progresses in an orderly manner, occasionally a small tumor with distant metastasis is seen. For this reason, patients must be carefully evaluated for metastatic disease.

Pretreatment surgical staging is the most accurate method to determine the extent of disease.[1] Because there is little evidence to demonstrate overall improved survival with routine surgical staging, the staging usually should be performed only as part of a clinical trial. Pretreatment surgical staging in bulky but locally curable disease may be indicated in select cases when a nonsurgical search for metastatic disease is negative. If abnormal nodes are detected by computed tomography scan or lymphangiography, fine-needle aspiration should be negative before a surgical staging procedure is performed.

Definitions: FIGO

The Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) and the American Joint Committee on Cancer (AJCC) have designated staging to define cervical cancer; the FIGO system is most commonly used.[2][3]

Table 1. Carcinoma of the Cervix Uteria

Stage

I

The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded).

IA

Invasive carcinoma, which can be diagnosed only by microscopy with deepest invasion ≤5 mm and largest extension ≥7 mm.

IA1

Measured stromal invasion of ≤3.0 mm in depth and extension of ≤7.0 mm.

IA2

Measured stromal invasion of >3.0 mm and not >5.0 mm with an extension of not >7.0 mm.

IB

Clinically visible lesions limited to the cervix uteri or preclinical cancers greater than stage IA.b

IB1

Clinically visible lesion ≤4.0 cm in greatest dimension.

IB2

Clinically visible lesion >4.0 cm in greatest dimension.

II

Cervical carcinoma invades beyond the uterus but not to the pelvic wall or to the lower third of the vagina.

IIA

Without parametrial invasion.

IIA1

Clinically visible lesion ≤4.0 cm in greatest dimension.

IIA2

Clinically visible lesion >4.0 cm in greatest dimension.

IIB

With obvious parametrial invasion.

III

The tumor extends to the pelvic wall and/or involves lower third of the vagina and/or causes hydronephrosis or nonfunctioning kidney.c

IIIA

Tumor involves lower third of the vagina with no extension to the pelvic wall.

IIIB

Extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney.

IV

The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to stage IV.

IVA

Spread of the growth to adjacent organs.

IVB

Spread to distant organs.

aAdapted from FIGO Committee on Gynecologic Oncology.[2]

bAll macroscopically visible lesions—even with superficial invasion—are allotted to stage IB carcinomas. Invasion is limited to a measured stromal invasion with a maximal depth of 5.00 mm and a horizontal extension of not >7.00 mm. Depth of invasion should not be >5.00 mm taken from the base of the epithelium of the original tissue—superficial or glandular. The depth of invasion should always be reported in mm, even in those cases with "early (minimal) stromal invasion" (~1 mm).

The involvement of vascular/lymphatic spaces should not change the stage allotment.

cOn rectal examination, there is no cancer-free space between the tumor and the pelvic wall. All cases with hydronephrosis or nonfunctioning kidney are included, unless they are known to be the result of another cause.

References:

  1. Gold MA, Tian C, Whitney CW, et al.: Surgical versus radiographic determination of para-aortic lymph node metastases before chemoradiation for locally advanced cervical carcinoma: a Gynecologic Oncology Group Study. Cancer 112 (9): 1954-63, 2008.

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

  3. Cervix uteri. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 395-402.

Treatment Option Overview

Standard treatments for patients with cervical cancer include:

  • Surgery.
  • Radiation therapy.
  • Chemotherapy.

Five randomized, phase III trials (GOG-85, RTOG-9001, GOG-120, GOG-123, and SWOG-8797) have shown an overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy,[1][2][3][4][5][6] while one trial examining this regimen demonstrated no benefit.[7] The patient populations in these studies included women with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) stages IB2 to IVA cervical cancer treated with primary radiation therapy and women with FIGO stages I to IIA disease found to have poor prognostic factors (metastatic disease in pelvic lymph nodes, parametrial disease, or positive surgical margins) at the time of primary surgery. Although the positive trials vary in terms of the stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrate significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy. Based on these results, strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.[1][2][3][4][5][6][7][8][9]

Surgery and radiation therapy are equally effective for early-stage small-volume disease.[10] Younger patients may benefit from surgery in regard to ovarian preservation and avoidance of vaginal atrophy and stenosis.

Patterns of care studies clearly demonstrate the negative prognostic effect of increasing tumor volume. Treatment, therefore, may vary within each stage as currently defined by FIGO and will depend on tumor bulk and spread pattern.[11]

Therapy of patients with cancer of the cervical stump is effective, yielding results comparable to those seen in patients with an intact uterus.[12]

Treatments under clinical evaluation for patients with cervical cancer include:

  • New anticancer drugs in phase I and phase II clinical trials.

Cervical cancer during pregnancy

During pregnancy, no therapy is warranted for preinvasive lesions of the cervix, including carcinoma in situ, though expert colposcopy is recommended to exclude invasive cancer. Treatment of invasive cervical cancer during pregnancy depends on the stage of the cancer and gestational age at diagnosis. The traditional approach is to recommend immediate therapy appropriate for the disease stage when the cancer is diagnosed before fetal maturity and to delay therapy only if the cancer is detected in the final trimester.[13][14] However, other reports suggest that deliberate delay of treatment to allow improved fetal outcome may be a reasonable option for patients with stage IA and early IB cervical cancer.[15]

References:

  1. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17 (5): 1339-48, 1999.

  2. Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340 (15): 1137-43, 1999.

  3. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340 (15): 1144-53, 1999.

  4. Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340 (15): 1154-61, 1999.

  5. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al.: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8): 1606-13, 2000.

  6. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.

  7. Pearcey R, Brundage M, Drouin P, et al.: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20 (4): 966-72, 2002.

  8. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.

  9. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration.: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26 (35): 5802-12, 2008.

  10. Eifel PJ, Burke TW, Delclos L, et al.: Early stage I adenocarcinoma of the uterine cervix: treatment results in patients with tumors less than or equal to 4 cm in diameter. Gynecol Oncol 41 (3): 199-205, 1991.

  11. Lanciano RM, Won M, Hanks GE: A reappraisal of the International Federation of Gynecology and Obstetrics staging system for cervical cancer. A study of patterns of care. Cancer 69 (2): 482-7, 1992.

  12. Kovalic JJ, Grigsby PW, Perez CA, et al.: Cervical stump carcinoma. Int J Radiat Oncol Biol Phys 20 (5): 933-8, 1991.

  13. Monk BJ, Montz FJ: Invasive cervical cancer complicating intrauterine pregnancy: treatment with radical hysterectomy. Obstet Gynecol 80 (2): 199-203, 1992.

  14. Hopkins MP, Morley GW: The prognosis and management of cervical cancer associated with pregnancy. Obstet Gynecol 80 (1): 9-13, 1992.

  15. Hunter MI, Tewari K, Monk BJ: Cervical neoplasia in pregnancy. Part 2: current treatment of invasive disease. Am J Obstet Gynecol 199 (1): 10-8, 2008.

Stage 0 Cervical Cancer

Consensus guidelines have been issued for managing women with cervical intraepithelial neoplasia or adenocarcinoma in situ.[1] Properly treated, tumor control of in situ cervical carcinoma should be nearly 100%. Either expert colposcopic-directed biopsy or cone biopsy is required to exclude invasive disease before therapy is undertaken. A correlation between cytology and colposcopic-directed biopsy is also necessary before local ablative therapy is done. Even so, unrecognized invasive disease treated with inadequate ablative therapy may be the most common cause of failure.[2] Failure to identify the disease, lack of correlation between the Pap smear and colposcopic findings, adenocarcinoma in situ, or extension of disease into the endocervical canal makes a laser, loop, or cold-knife conization mandatory. The choice of treatment will also depend on several patient factors including age, desire to preserve fertility, and medical condition. Most importantly, the extent of disease must be known.

In selected cases, the outpatient loop electrosurgical excision procedure (LEEP) may be an acceptable alternative to cold-knife conization. This quickly performed in-office procedure requires only local anesthesia and obviates the risks associated with general anesthesia for cold-knife conization.[3][4] However, controversy exists as to the adequacy of LEEP as a replacement for conization.[5] A trial comparing LEEP with cold-knife cone biopsy showed no difference in the likelihood of complete excision of dysplasia.[6] However, two case reports suggested that the use of LEEP in patients with occult invasive cancer led to an inability to accurately determine depth of invasion when a focus of the cancer was transected.[7]

Standard treatment options:

Methods to treat ectocervical lesions include the following:

  1. LEEP.[8][9]
  2. Laser therapy.[10]
  3. Conization.
  4. Cryotherapy.[11]
  5. Total abdominal or vaginal hysterectomy for postreproductive patients.
  6. Internal radiation therapy for medically inoperable patients.

When the endocervical canal is involved, laser or cold-knife conization may be used for selected patients to preserve the uterus and avoid radiation therapy and/or more extensive surgery.

Total abdominal or vaginal hysterectomy is an accepted therapy for the postreproductive age group and is particularly indicated when the neoplastic process extends to the inner cone margin. For medically inoperable patients, a single intracavitary insertion with tandem and ovoids for 5,000 mg hours (80 Gy vaginal surface dose) may be used.[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 0 cervical 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. Wright TC Jr, Massad LS, Dunton CJ, et al.: 2006 consensus guidelines for the management of women with cervical intraepithelial neoplasia or adenocarcinoma in situ. Am J Obstet Gynecol 197 (4): 340-5, 2007.

  2. Shumsky AG, Stuart GC, Nation J: Carcinoma of the cervix following conservative management of cervical intraepithelial neoplasia. Gynecol Oncol 53 (1): 50-4, 1994.

  3. Wright TC Jr, Gagnon S, Richart RM, et al.: Treatment of cervical intraepithelial neoplasia using the loop electrosurgical excision procedure. Obstet Gynecol 79 (2): 173-8, 1992.

  4. Naumann RW, Bell MC, Alvarez RD, et al.: LLETZ is an acceptable alternative to diagnostic cold-knife conization. Gynecol Oncol 55 (2): 224-8, 1994.

  5. Widrich T, Kennedy AW, Myers TM, et al.: Adenocarcinoma in situ of the uterine cervix: management and outcome. Gynecol Oncol 61 (3): 304-8, 1996.

  6. Girardi F, Heydarfadai M, Koroschetz F, et al.: Cold-knife conization versus loop excision: histopathologic and clinical results of a randomized trial. Gynecol Oncol 55 (3 Pt 1): 368-70, 1994.

  7. Eddy GL, Spiegel GW, Creasman WT: Adverse effect of electrosurgical loop excision on assignment of FIGO stage in cervical cancer: report of two cases. Gynecol Oncol 55 (2): 313-7, 1994.

  8. Wright VC, Chapman W: Intraepithelial neoplasia of the lower female genital tract: etiology, investigation, and management. Semin Surg Oncol 8 (4): 180-90, 1992 Jul-Aug.

  9. Bloss JD: The use of electrosurgical techniques in the management of premalignant diseases of the vulva, vagina, and cervix: an excisional rather than an ablative approach. Am J Obstet Gynecol 169 (5): 1081-5, 1993.

  10. Tsukamoto N: Treatment of cervical intraepithelial neoplasia with the carbon dioxide laser. Gynecol Oncol 21 (3): 331-6, 1985.

  11. Benedet JL, Miller DM, Nickerson KG, et al.: The results of cryosurgical treatment of cervical intraepithelial neoplasia at one, five, and ten years. Am J Obstet Gynecol 157 (2): 268-73, 1987.

  12. Grigsby PW, Perez CA: Radiotherapy alone for medically inoperable carcinoma of the cervix: stage IA and carcinoma in situ. Int J Radiat Oncol Biol Phys 21 (2): 375-8, 1991.

Stage IA Cervical Cancer

Equivalent treatment options:

  1. Total hysterectomy.[1] If the depth of invasion is less than 3 mm proven by cone biopsy with clear margins [2] and no vascular or lymphatic channel invasion is noted, the frequency of lymph node involvement is sufficiently low that lymph node dissection is not required. Oophorectomy is optional and should be deferred for younger women.
  2. Conization. If the depth of invasion is less than 3 mm, no vascular or lymphatic channel invasion is noted, and the margins of the cone are negative, conization alone may be appropriate in patients wishing to preserve fertility.[1]
  3. Modified radical hysterectomy. For patients with tumor invasion between 3 mm and 5 mm, radical hysterectomy with pelvic node dissection has been recommended because of a reported risk of lymph node metastasis of as much as 10%.[2] However, a study suggests that the rate of lymph-node involvement in this group of patients may be much lower and questions whether conservative therapy might be adequate for patients believed to have no residual disease following conization.[3] Radical hysterectomy with node dissection may also be considered for patients where the depth of tumor invasion was uncertain because of invasive tumor at the cone margins.
  4. Intracavitary radiation therapy alone. If the depth of invasion is less than 3 mm and no capillary lymphatic space invasion is noted, the frequency of lymph node involvement is sufficiently low that external-beam radiation therapy is not required. One or two insertions with tandem and ovoids for 6,500 mg to 8,000 mg hours (100 Gy–125 Gy vaginal surface dose) are recommended.[4] Radiation therapy should be reserved for women who are not surgical candidates.

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IA cervical 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. Sevin BU, Nadji M, Averette HE, et al.: Microinvasive carcinoma of the cervix. Cancer 70 (8): 2121-8, 1992.

  2. Jones WB, Mercer GO, Lewis JL Jr, et al.: Early invasive carcinoma of the cervix. Gynecol Oncol 51 (1): 26-32, 1993.

  3. Creasman WT, Zaino RJ, Major FJ, et al.: Early invasive carcinoma of the cervix (3 to 5 mm invasion): risk factors and prognosis. A Gynecologic Oncology Group study. Am J Obstet Gynecol 178 (1 Pt 1): 62-5, 1998.

  4. Grigsby PW, Perez CA: Radiotherapy alone for medically inoperable carcinoma of the cervix: stage IA and carcinoma in situ. Int J Radiat Oncol Biol Phys 21 (2): 375-8, 1991.

Stage IB Cervical Cancer

Either radiation therapy or radical hysterectomy and bilateral lymph node dissection results in cure rates of 85% to 90% for women with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) stages IA2 and IB1 small-volume disease. The choice of either treatment depends on patient factors and available local expertise. A randomized trial reported identical 5-year overall survival (OS) and disease-free survival rates when comparing radiation therapy to radical hysterectomy.[1] The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[2] For adenocarcinomas that expand the cervix more than 4 cm, the primary treatment should be concomitant chemotherapy and radiation therapy.[3]

After surgical staging, patients found to have small volume para-aortic nodal disease and controllable pelvic disease may be cured with pelvic and para-aortic radiation therapy and concomitant chemotherapy.[4] The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative chemotherapy and radiation therapy.[5] Treatment of patients with unresected periaortic nodes with extended-field radiation therapy and chemotherapy leads to long-term disease control in those patients with low volume (<2 cm) nodal disease below L3.[6] A single study (RTOG-7920) showed a survival advantage in patients with tumors larger than 4 cm who received radiation therapy to para-aortic nodes without histologic evidence of disease.[7] Toxic effects were greater with para-aortic radiation therapy than with pelvic radiation therapy alone but were mostly confined to patients with prior abdominopelvic surgery.[7] Patients who underwent extraperitoneal lymph node sampling had fewer bowel complications than those who had transperitoneal lymph node sampling.[6][8][9] Patients with close vaginal margins (<0.5 cm) may also benefit from pelvic radiation therapy.[10]

Five randomized, phase III trials have shown an OS advantage for cisplatin-based therapy given concurrently with radiation therapy,[11][12][13][14][15][16] while one trial examining this regimen demonstrated no benefit.[17] The patient populations in these studies included women with FIGO stages IB2 to IVA cervical cancer treated with primary radiation therapy, and women with FIGO stages I to IIA disease who, at the time of primary surgery, were found to have poor prognostic factors, which included the following:

  • Metastatic disease in pelvic lymph nodes.
  • Parametrial disease.
  • Positive surgical margins.

Although the positive trials vary somewhat in terms of the stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrate significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy. Based on these results, strong consideration should be given to the incorporation of concurrent, cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.[11][12][13][14][15][16][17][18][19]

Standard treatment options:

  1. Radiation therapy. External-beam pelvic radiation therapy combined with two or more intracavitary brachytherapy applications is appropriate therapy for stage IA2 and IB1 lesions. Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantage of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and outpatient management. In three randomized trials, HDR brachytherapy was comparable with LDR brachytherapy in terms of local-regional control and complication rates.[20][21][22][Level of evidence: 1iiDii] The American Brachytherapy Society has published guidelines for the use of LDR and HDR brachytherapy as components of cervical cancer treatment.[23][24] For stage IB2 lesions, radiosensitizing chemotherapy is indicated. The role of radiosensitizing chemotherapy in IA2 and IB1 lesions is untested and likely to be of only marginal benefit since the cure rates with radiation alone exceed or approach 90%.
  2. Radical hysterectomy and bilateral pelvic lymphadenectomy.
  3. Postoperative total pelvic radiation therapy plus chemotherapy following radical hysterectomy and bilateral pelvic lymphadenectomy. Radiation in the range of 50 Gy administered for 5 weeks plus chemotherapy with cisplatin with or without fluorouracil (5-FU) should be considered in patients at high risk of recurrence including those with positive pelvic nodes, positive surgical margins, and residual parametrial disease.[11][12][13][14][15][16]
  4. Radiation therapy plus chemotherapy with cisplatin or cisplatin/5-FU for patients with bulky tumors.[11][12][13][14][15][16][25]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IB cervical 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. Landoni F, Maneo A, Colombo A, et al.: Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 350 (9077): 535-40, 1997.

  2. Perez CA, Grigsby PW, Nene SM, et al.: Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 69 (11): 2796-806, 1992.

  3. Eifel PJ, Burke TW, Delclos L, et al.: Early stage I adenocarcinoma of the uterine cervix: treatment results in patients with tumors less than or equal to 4 cm in diameter. Gynecol Oncol 41 (3): 199-205, 1991.

  4. Cunningham MJ, Dunton CJ, Corn B, et al.: Extended-field radiation therapy in early-stage cervical carcinoma: survival and complications. Gynecol Oncol 43 (1): 51-4, 1991.

  5. Downey GO, Potish RA, Adcock LL, et al.: Pretreatment surgical staging in cervical carcinoma: therapeutic efficacy of pelvic lymph node resection. Am J Obstet Gynecol 160 (5 Pt 1): 1055-61, 1989.

  6. Vigliotti AP, Wen BC, Hussey DH, et al.: Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes. Int J Radiat Oncol Biol Phys 23 (3): 501-9, 1992.

  7. Rotman M, Pajak TF, Choi K, et al.: Prophylactic extended-field irradiation of para-aortic lymph nodes in stages IIB and bulky IB and IIA cervical carcinomas. Ten-year treatment results of RTOG 79-20. JAMA 274 (5): 387-93, 1995.

  8. Weiser EB, Bundy BN, Hoskins WJ, et al.: Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study). Gynecol Oncol 33 (3): 283-9, 1989.

  9. Fine BA, Hempling RE, Piver MS, et al.: Severe radiation morbidity in carcinoma of the cervix: impact of pretherapy surgical staging and previous surgery. Int J Radiat Oncol Biol Phys 31 (4): 717-23, 1995.

  10. Estape RE, Angioli R, Madrigal M, et al.: Close vaginal margins as a prognostic factor after radical hysterectomy. Gynecol Oncol 68 (3): 229-32, 1998.

  11. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17 (5): 1339-48, 1999.

  12. Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340 (15): 1137-43, 1999.

  13. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340 (15): 1144-53, 1999.

  14. Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340 (15): 1154-61, 1999.

  15. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al.: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8): 1606-13, 2000.

  16. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.

  17. Pearcey R, Brundage M, Drouin P, et al.: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20 (4): 966-72, 2002.

  18. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.

  19. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration.: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26 (35): 5802-12, 2008.

  20. Patel FD, Sharma SC, Negi PS, et al.: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys 28 (2): 335-41, 1994.

  21. Hareyama M, Sakata K, Oouchi A, et al.: High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial. Cancer 94 (1): 117-24, 2002.

  22. Lertsanguansinchai P, Lertbutsayanukul C, Shotelersuk K, et al.: Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma. Int J Radiat Oncol Biol Phys 59 (5): 1424-31, 2004.

  23. Nag S, Chao C, Erickson B, et al.: The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 52 (1): 33-48, 2002.

  24. Nag S, Erickson B, Thomadsen B, et al.: The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 48 (1): 201-11, 2000.

  25. Monk BJ, Tewari KS, Koh WJ: Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol 25 (20): 2952-65, 2007.

Stage IIA Cervical Cancer

Either radiation therapy or radical hysterectomy results in cure rates of 75% to 80%. The selection of either option depends on patient factors and local expertise. A randomized trial reported identical 5-year overall survival (OS) and disease-free survival rates when radiation therapy was compared with radical hysterectomy.[1] The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[2] For patients with bulky (>6 cm) endocervical squamous cell carcinomas or adenocarcinomas, treatment with high-dose radiation therapy will achieve local control and survival rates comparable to treatment with radiation therapy plus hysterectomy. Surgery after radiation therapy may be indicated for some patients with tumors confined to the cervix that respond incompletely to radiation therapy or in whom vaginal anatomy precludes optimal brachytherapy.[3]

After surgical staging, patients found to have small volume para-aortic nodal disease and controllable pelvic disease may be cured with pelvic and para-aortic radiation therapy.[4] The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative radiation therapy.[5] Treatment of patients with unresected periaortic nodes with extended-field radiation therapy leads to long-term disease control in those patients with low volume (<2 cm) nodal disease below L3.[6] A single study (RTOG-7920) showed a survival advantage in patients who received radiation therapy to para-aortic nodes without histologic evidence of disease.[7] Toxic effects were greater with para-aortic radiation than with pelvic radiation alone but were mostly confined to patients with prior abdominopelvic surgery.[7] Patients who underwent extraperitoneal lymph node sampling had fewer bowel complications than those who had transperitoneal lymph node sampling.[6][8][9] Patients with close vaginal margins (<0.5 cm) after radical surgery may also benefit from pelvic radiation therapy.[10]

Five randomized, phase III trials have shown an OS advantage for cisplatin-based therapy given concurrently with radiation therapy,[11][12][13][14][15][16][17] while one trial examining this regimen demonstrated no benefit.[18] The patient populations in these studies included women with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) stages IB2 to IVA cervical cancer treated with primary radiation therapy and women with FIGO stages I to IIA disease who, at the time of primary surgery, were found to have poor prognostic factors, which included the following:

  • Metastatic disease in pelvic lymph nodes.
  • Parametrial disease.
  • Positive surgical margins.

Although the positive trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrate significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy. Based on these results, strong consideration should be given to the incorporation of concurrent, cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.[11][12][13][14][15][16][17][18][19]

Standard treatment options:

  1. Intracavitary radiation therapy combined with external-beam pelvic radiation therapy plus chemotherapy with cisplatin or cisplatin/5-FU for patients with bulky tumors.[11][12][13][14][15][16][20] Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantage of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and outpatient management. In three randomized trials, HDR brachytherapy was comparable to LDR brachytherapy in terms of local-regional control and complication rates.[21][22][23][Level of evidence: 1iiDii] The American Brachytherapy Society has published guidelines for the use of LDR and HDR brachytherapy as components of cervical cancer treatment.[24][25] Radiation therapy to para-aortic nodes may be indicated in primary tumors 4 cm or larger.
  2. Radical hysterectomy and pelvic lymphadenectomy. Radical surgery has been performed for small lesions, but the high incidence of compromised margins, parametrial spread, and positive nodes leading to postoperative radiation with or without chemotherapy make primary concomitant chemotherapy and radiation a more common approach.
  3. Postoperative total pelvic radiation therapy plus chemotherapy following radical hysterectomy and bilateral pelvic lymphadenectomy. Radiation therapy in the range of 50 Gy administered for 5 weeks plus chemotherapy with cisplatin with or without fluorouracil (5-FU) should be considered in patients with positive pelvic nodes, positive surgical margins, and residual parametrial disease.[11][12][13][14][15][16]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIA cervical 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. Landoni F, Maneo A, Colombo A, et al.: Randomised study of radical surgery versus radiotherapy for stage Ib-IIa cervical cancer. Lancet 350 (9077): 535-40, 1997.

  2. Perez CA, Grigsby PW, Nene SM, et al.: Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 69 (11): 2796-806, 1992.

  3. Thoms WW Jr, Eifel PJ, Smith TL, et al.: Bulky endocervical carcinoma: a 23-year experience. Int J Radiat Oncol Biol Phys 23 (3): 491-9, 1992.

  4. Cunningham MJ, Dunton CJ, Corn B, et al.: Extended-field radiation therapy in early-stage cervical carcinoma: survival and complications. Gynecol Oncol 43 (1): 51-4, 1991.

  5. Downey GO, Potish RA, Adcock LL, et al.: Pretreatment surgical staging in cervical carcinoma: therapeutic efficacy of pelvic lymph node resection. Am J Obstet Gynecol 160 (5 Pt 1): 1055-61, 1989.

  6. Vigliotti AP, Wen BC, Hussey DH, et al.: Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes. Int J Radiat Oncol Biol Phys 23 (3): 501-9, 1992.

  7. Rotman M, Pajak TF, Choi K, et al.: Prophylactic extended-field irradiation of para-aortic lymph nodes in stages IIB and bulky IB and IIA cervical carcinomas. Ten-year treatment results of RTOG 79-20. JAMA 274 (5): 387-93, 1995.

  8. Weiser EB, Bundy BN, Hoskins WJ, et al.: Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study). Gynecol Oncol 33 (3): 283-9, 1989.

  9. Fine BA, Hempling RE, Piver MS, et al.: Severe radiation morbidity in carcinoma of the cervix: impact of pretherapy surgical staging and previous surgery. Int J Radiat Oncol Biol Phys 31 (4): 717-23, 1995.

  10. Estape RE, Angioli R, Madrigal M, et al.: Close vaginal margins as a prognostic factor after radical hysterectomy. Gynecol Oncol 68 (3): 229-32, 1998.

  11. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17 (5): 1339-48, 1999.

  12. Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340 (15): 1137-43, 1999.

  13. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340 (15): 1144-53, 1999.

  14. Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340 (15): 1154-61, 1999.

  15. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al.: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8): 1606-13, 2000.

  16. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.

  17. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration.: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26 (35): 5802-12, 2008.

  18. Pearcey R, Brundage M, Drouin P, et al.: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20 (4): 966-72, 2002.

  19. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.

  20. Monk BJ, Tewari KS, Koh WJ: Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol 25 (20): 2952-65, 2007.

  21. Patel FD, Sharma SC, Negi PS, et al.: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys 28 (2): 335-41, 1994.

  22. Hareyama M, Sakata K, Oouchi A, et al.: High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial. Cancer 94 (1): 117-24, 2002.

  23. Lertsanguansinchai P, Lertbutsayanukul C, Shotelersuk K, et al.: Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma. Int J Radiat Oncol Biol Phys 59 (5): 1424-31, 2004.

  24. Nag S, Chao C, Erickson B, et al.: The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 52 (1): 33-48, 2002.

  25. Nag S, Erickson B, Thomadsen B, et al.: The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 48 (1): 201-11, 2000.

Stage IIB Cervical Cancer

The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[1] Survival and local control are better with unilateral rather than bilateral parametrial involvement.[2] Patients who are surgically staged as part of a clinical trial and are found to have small volume para-aortic nodal disease and controllable pelvic disease may be cured with pelvic and para-aortic radiation therapy.[3] If postoperative external-beam radiation therapy (EBRT) is planned following surgery, extraperitoneal lymph node sampling is associated with fewer radiation-induced complications than a transperitoneal approach.[4] The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative radiation therapy.[5] Treatment of patients with unresected periaortic nodes with extended-field radiation therapy leads to long-term disease control in those patients with low volume (<2 cm) nodal disease below L3.[6] A single study (RTOG-7920) showed a survival advantage in patients who received radiation therapy to para-aortic nodes without histologic evidence of disease.[7] Toxic effects are greater with para-aortic radiation than with pelvic radiation alone but were mostly confined to patients with prior abdominopelvic surgery.[7] Patients who underwent extraperitoneal lymph node sampling had fewer bowel complications than those who had transperitoneal lymph node sampling.[4][6][8]

Five randomized, phase III trials have shown an overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy, [9][10][11][12][13][14][15] while one trial examining this regimen demonstrated no benefit.[16] The patient populations in these studies included women with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) stages IB2 to IVA cervical cancer treated with primary radiation therapy, and women with FIGO stages I to IIA disease who, at the time of primary surgery, were found to have poor prognostic factors, which included the following:

  • Metastatic disease in pelvic lymph nodes.
  • Parametrial disease.
  • Positive surgical margins.

Although the positive trials vary somewhat in terms of the stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrated significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy. Based on these results, strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.[9][10][11][12][13][14][15][16][17]

Standard treatment options:

  • Radiation therapy plus chemotherapy: Intracavitary radiation therapy and EBRT to the pelvis combined with cisplatin or cisplatin/fluorouracil.[9][10][11][12][13][14][18]

Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantage of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and outpatient management. In three randomized trials, HDR brachytherapy was comparable with LDR brachytherapy in terms of local-regional control and complication rates.[19][20][21][Level of evidence: 1iiDii] The American Brachytherapy Society has published guidelines for the use of LDR and HDR brachytherapy as a component of cervical cancer treatment.[22][23]

Current Clinical Trials

Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with stage IIB cervical 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. Perez CA, Grigsby PW, Nene SM, et al.: Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 69 (11): 2796-806, 1992.

  2. Lanciano RM, Won M, Hanks GE: A reappraisal of the International Federation of Gynecology and Obstetrics staging system for cervical cancer. A study of patterns of care. Cancer 69 (2): 482-7, 1992.

  3. Cunningham MJ, Dunton CJ, Corn B, et al.: Extended-field radiation therapy in early-stage cervical carcinoma: survival and complications. Gynecol Oncol 43 (1): 51-4, 1991.

  4. Weiser EB, Bundy BN, Hoskins WJ, et al.: Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study). Gynecol Oncol 33 (3): 283-9, 1989.

  5. Downey GO, Potish RA, Adcock LL, et al.: Pretreatment surgical staging in cervical carcinoma: therapeutic efficacy of pelvic lymph node resection. Am J Obstet Gynecol 160 (5 Pt 1): 1055-61, 1989.

  6. Vigliotti AP, Wen BC, Hussey DH, et al.: Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes. Int J Radiat Oncol Biol Phys 23 (3): 501-9, 1992.

  7. Rotman M, Pajak TF, Choi K, et al.: Prophylactic extended-field irradiation of para-aortic lymph nodes in stages IIB and bulky IB and IIA cervical carcinomas. Ten-year treatment results of RTOG 79-20. JAMA 274 (5): 387-93, 1995.

  8. Fine BA, Hempling RE, Piver MS, et al.: Severe radiation morbidity in carcinoma of the cervix: impact of pretherapy surgical staging and previous surgery. Int J Radiat Oncol Biol Phys 31 (4): 717-23, 1995.

  9. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17 (5): 1339-48, 1999.

  10. Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340 (15): 1137-43, 1999.

  11. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340 (15): 1144-53, 1999.

  12. Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340 (15): 1154-61, 1999.

  13. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al.: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8): 1606-13, 2000.

  14. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.

  15. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration.: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26 (35): 5802-12, 2008.

  16. Pearcey R, Brundage M, Drouin P, et al.: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20 (4): 966-72, 2002.

  17. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.

  18. Monk BJ, Tewari KS, Koh WJ: Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol 25 (20): 2952-65, 2007.

  19. Patel FD, Sharma SC, Negi PS, et al.: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys 28 (2): 335-41, 1994.

  20. Hareyama M, Sakata K, Oouchi A, et al.: High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial. Cancer 94 (1): 117-24, 2002.

  21. Lertsanguansinchai P, Lertbutsayanukul C, Shotelersuk K, et al.: Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma. Int J Radiat Oncol Biol Phys 59 (5): 1424-31, 2004.

  22. Nag S, Chao C, Erickson B, et al.: The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 52 (1): 33-48, 2002.

  23. Nag S, Erickson B, Thomadsen B, et al.: The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 48 (1): 201-11, 2000.

Stage III Cervical Cancer

The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[1] Patterns-of-care studies in stage IIIA/IIIB patients indicate that survival is dependent on the extent of the disease, with unilateral pelvic wall involvement predicting a better outcome than bilateral involvement, which in turn predicts a better outcome than involvement of the lower third of the vaginal wall.[2] These studies also reveal a progressive increase in local control and survival paralleling a progressive increase in paracentral (point A) dose and use of intracavitary treatment. The highest rate of central control was seen with paracentral (point A) doses of more than 85 Gy.[3]

Patients who are surgically staged as part of a clinical trial and are found to have small volume para-aortic nodal disease and controllable pelvic disease may be cured with external-beam pelvic and para-aortic radiation therapy. If postoperative external-beam radiation therapy (EBRT) is planned following surgery, extraperitoneal lymph node sampling is associated with fewer radiation-induced complications than a transperitoneal approach.[4] The resection of macroscopically involved pelvic nodes may improve rates of local control with postoperative radiation therapy.[5] Treatment of patients with unresected periaortic nodes with extended-field radiation therapy leads to long-term disease control in those patients with low volume (<2 cm) nodal disease below L3. Patients who underwent extraperitoneal lymph node sampling had fewer bowel complications than those who had transperitoneal lymph node sampling.[6]

Five randomized, phase III trials have shown an overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy,[7][8][9][10][11][12][13] while one trial examining this regimen demonstrated no benefit.[14] The patient populations in these studies included women with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) stages IB2 to IVA cervical cancer treated with primary radiation therapy and women with FIGO stages I to IIA disease who, at the time of primary surgery, were found to have poor prognostic factors, which included the following:

  • Metastatic disease in pelvic lymph nodes.
  • Parametrial disease.
  • Positive surgical margins.

Although the positive trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrate significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy. Based on these results, strong consideration should be given to the incorporation of concurrent cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.[7][8][9][10][11][12][13][14][15]

Standard treatment options:

  • Radiation therapy plus chemotherapy. Intracavitary radiation and EBRT to the pelvis combined with cisplatin or cisplatin/fluorouracil.[7][8][9][10][11][12][16]

Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantages of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and outpatient management. In three randomized trials, HDR brachytherapy was comparable with LDR brachytherapy in terms of local-regional control and complication rates.[17][18][19][Level of evidence: 1iiDii] The American Brachytherapy Society has published guidelines for the use of LDR and HDR brachytherapy as a component of cervical cancer treatment.[20][21]

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 cervical 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. Perez CA, Grigsby PW, Nene SM, et al.: Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 69 (11): 2796-806, 1992.

  2. Lanciano RM, Won M, Hanks GE: A reappraisal of the International Federation of Gynecology and Obstetrics staging system for cervical cancer. A study of patterns of care. Cancer 69 (2): 482-7, 1992.

  3. Lanciano RM, Martz K, Coia LR, et al.: Tumor and treatment factors improving outcome in stage III-B cervix cancer. Int J Radiat Oncol Biol Phys 20 (1): 95-100, 1991.

  4. Weiser EB, Bundy BN, Hoskins WJ, et al.: Extraperitoneal versus transperitoneal selective paraaortic lymphadenectomy in the pretreatment surgical staging of advanced cervical carcinoma (a Gynecologic Oncology Group study). Gynecol Oncol 33 (3): 283-9, 1989.

  5. Downey GO, Potish RA, Adcock LL, et al.: Pretreatment surgical staging in cervical carcinoma: therapeutic efficacy of pelvic lymph node resection. Am J Obstet Gynecol 160 (5 Pt 1): 1055-61, 1989.

  6. Vigliotti AP, Wen BC, Hussey DH, et al.: Extended field irradiation for carcinoma of the uterine cervix with positive periaortic nodes. Int J Radiat Oncol Biol Phys 23 (3): 501-9, 1992.

  7. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17 (5): 1339-48, 1999.

  8. Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340 (15): 1137-43, 1999.

  9. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340 (15): 1144-53, 1999.

  10. Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340 (15): 1154-61, 1999.

  11. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al.: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8): 1606-13, 2000.

  12. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.

  13. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration.: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26 (35): 5802-12, 2008.

  14. Pearcey R, Brundage M, Drouin P, et al.: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20 (4): 966-72, 2002.

  15. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.

  16. Monk BJ, Tewari KS, Koh WJ: Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol 25 (20): 2952-65, 2007.

  17. Patel FD, Sharma SC, Negi PS, et al.: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys 28 (2): 335-41, 1994.

  18. Hareyama M, Sakata K, Oouchi A, et al.: High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial. Cancer 94 (1): 117-24, 2002.

  19. Lertsanguansinchai P, Lertbutsayanukul C, Shotelersuk K, et al.: Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma. Int J Radiat Oncol Biol Phys 59 (5): 1424-31, 2004.

  20. Nag S, Chao C, Erickson B, et al.: The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 52 (1): 33-48, 2002.

  21. Nag S, Erickson B, Thomadsen B, et al.: The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 48 (1): 201-11, 2000.

Stage IVA Cervical Cancer

The size of the primary tumor is an important prognostic factor and should be carefully evaluated in choosing optimal therapy.[1] After surgical staging, patients found to have small volume para-aortic nodal disease and controllable pelvic disease may be cured with pelvic and para-aortic radiation therapy.

Five randomized, phase III trials have shown an overall survival advantage for cisplatin-based therapy given concurrently with radiation therapy,[2][3][4][5][6][7][8] while one trial examining this regimen demonstrated no benefit.[9] The patient populations in these studies included women with Féderation Internationale de Gynécologie et d’Obstétrique (FIGO) stages IB2 to IVA cervical cancer treated with primary radiation therapy and women with FIGO stages I to IIA disease who, at the time of primary surgery, were found to have poor prognostic factors, which include the following:

  • Metastatic disease in pelvic lymph nodes.
  • Parametrial disease.
  • Positive surgical margins.

Although the positive trials vary somewhat in terms of stage of disease, dose of radiation, and schedule of cisplatin and radiation, the trials demonstrate significant survival benefit for this combined approach. The risk of death from cervical cancer was decreased by 30% to 50% with the use of concurrent chemoradiation therapy. Based on these results, strong consideration should be given to the incorporation of concurrent, cisplatin-based chemotherapy with radiation therapy in women who require radiation therapy for treatment of cervical cancer.[2][3][4][5][6][7][8][9][10]

Standard treatment options:

  • Radiation therapy plus chemotherapy: Intracavitary radiation therapy and external-beam pelvic radiation therapy combined with cisplatin or cisplatin/fluorouracil.[2][3][4][5][6][7][11]

Although low-dose rate (LDR) brachytherapy, typically with cesium Cs 137, has been the traditional approach, the use of high-dose rate (HDR) therapy, typically with iridium Ir 192, is rapidly increasing. HDR brachytherapy provides the advantage of eliminating radiation exposure to medical personnel, a shorter treatment time, patient convenience, and outpatient management. In three randomized trials, HDR brachytherapy was comparable with LDR brachytherapy in terms of local-regional control and complication rates.[12][13][14][Level of evidence: 1iiDii] The American Brachytherapy Society has published guidelines for the use of LDR and HDR brachytherapy as a component of cervical cancer treatment.[11][15][16]

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 cervical 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. Perez CA, Grigsby PW, Nene SM, et al.: Effect of tumor size on the prognosis of carcinoma of the uterine cervix treated with irradiation alone. Cancer 69 (11): 2796-806, 1992.

  2. Whitney CW, Sause W, Bundy BN, et al.: Randomized comparison of fluorouracil plus cisplatin versus hydroxyurea as an adjunct to radiation therapy in stage IIB-IVA carcinoma of the cervix with negative para-aortic lymph nodes: a Gynecologic Oncology Group and Southwest Oncology Group study. J Clin Oncol 17 (5): 1339-48, 1999.

  3. Morris M, Eifel PJ, Lu J, et al.: Pelvic radiation with concurrent chemotherapy compared with pelvic and para-aortic radiation for high-risk cervical cancer. N Engl J Med 340 (15): 1137-43, 1999.

  4. Rose PG, Bundy BN, Watkins EB, et al.: Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med 340 (15): 1144-53, 1999.

  5. Keys HM, Bundy BN, Stehman FB, et al.: Cisplatin, radiation, and adjuvant hysterectomy compared with radiation and adjuvant hysterectomy for bulky stage IB cervical carcinoma. N Engl J Med 340 (15): 1154-61, 1999.

  6. Peters WA 3rd, Liu PY, Barrett RJ 2nd, et al.: Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix. J Clin Oncol 18 (8): 1606-13, 2000.

  7. Thomas GM: Improved treatment for cervical cancer--concurrent chemotherapy and radiotherapy. N Engl J Med 340 (15): 1198-200, 1999.

  8. Chemoradiotherapy for Cervical Cancer Meta-Analysis Collaboration.: Reducing uncertainties about the effects of chemoradiotherapy for cervical cancer: a systematic review and meta-analysis of individual patient data from 18 randomized trials. J Clin Oncol 26 (35): 5802-12, 2008.

  9. Pearcey R, Brundage M, Drouin P, et al.: Phase III trial comparing radical radiotherapy with and without cisplatin chemotherapy in patients with advanced squamous cell cancer of the cervix. J Clin Oncol 20 (4): 966-72, 2002.

  10. Rose PG, Bundy BN: Chemoradiation for locally advanced cervical cancer: does it help? J Clin Oncol 20 (4): 891-3, 2002.

  11. Monk BJ, Tewari KS, Koh WJ: Multimodality therapy for locally advanced cervical carcinoma: state of the art and future directions. J Clin Oncol 25 (20): 2952-65, 2007.

  12. Patel FD, Sharma SC, Negi PS, et al.: Low dose rate vs. high dose rate brachytherapy in the treatment of carcinoma of the uterine cervix: a clinical trial. Int J Radiat Oncol Biol Phys 28 (2): 335-41, 1994.

  13. Hareyama M, Sakata K, Oouchi A, et al.: High-dose-rate versus low-dose-rate intracavitary therapy for carcinoma of the uterine cervix: a randomized trial. Cancer 94 (1): 117-24, 2002.

  14. Lertsanguansinchai P, Lertbutsayanukul C, Shotelersuk K, et al.: Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma. Int J Radiat Oncol Biol Phys 59 (5): 1424-31, 2004.

  15. Nag S, Chao C, Erickson B, et al.: The American Brachytherapy Society recommendations for low-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 52 (1): 33-48, 2002.

  16. Nag S, Erickson B, Thomadsen B, et al.: The American Brachytherapy Society recommendations for high-dose-rate brachytherapy for carcinoma of the cervix. Int J Radiat Oncol Biol Phys 48 (1): 201-11, 2000.

Stage IVB Cervical Cancer

No standard chemotherapy treatment that provides substantial palliation is available for patients with stage IVB cervical cancer. These patients are appropriate candidates for clinical trials testing single agents or combination chemotherapy employing agents listed below or new anticancer treatments in phase I and II clinical trials.[1]

Standard treatment options:

  1. Radiation therapy may be used to palliate central disease or distant metastases.
  2. Chemotherapy. Tested drugs include the following:
    • Cisplatin (15%–25% response rate).[1][2]
    • Ifosfamide (31% response rate).[3]
    • Paclitaxel (17% response rate).[4][5][6]
    • Ifosfamide-cisplatin.[7][8]
    • Irinotecan (21% response rate in patients previously treated with chemotherapy).[9]
    • Paclitaxel/cisplatin (46% response rate).[10]
    • Cisplatin/gemcitabine (41% response rate).[11]
    • Cisplatin/topotecan (27% response rate).[12]

Treatment options under clinical evaluation:

  • New anticancer drugs in phase I and phase II 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 IVB cervical 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. Alberts DS, Kronmal R, Baker LH, et al.: Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study. J Clin Oncol 5 (11): 1791-5, 1987.

  2. Thigpen JT, Blessing JA, DiSaia PJ, et al.: A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol 32 (2): 198-202, 1989.

  3. Coleman RE, Harper PG, Gallagher C, et al.: A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol 18 (3): 280-3, 1986.

  4. Kudelka AP, Winn R, Edwards CL, et al.: Activity of paclitaxel in advanced or recurrent squamous cell cancer of the cervix. Clin Cancer Res 2 (8): 1285-8, 1996.

  5. Thigpen T, Vance RB, Khansur T: The platinum compounds and paclitaxel in the management of carcinomas of the endometrium and uterine cervix. Semin Oncol 22 (5 Suppl 12): 67-75, 1995.

  6. McGuire WP, Blessing JA, Moore D, et al.: Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol 14 (3): 792-5, 1996.

  7. Buxton EJ, Meanwell CA, Hilton C, et al.: Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer. J Natl Cancer Inst 81 (5): 359-61, 1989.

  8. Omura GA, Blessing JA, Vaccarello L, et al.: Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 15 (1): 165-71, 1997.

  9. Verschraegen CF, Levy T, Kudelka AP, et al.: Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol 15 (2): 625-31, 1997.

  10. Rose PG, Blessing JA, Gershenson DM, et al.: Paclitaxel and cisplatin as first-line therapy in recurrent or advanced squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 17 (9): 2676-80, 1999.

  11. Burnett AF, Roman LD, Garcia AA, et al.: A phase II study of gemcitabine and cisplatin in patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix. Gynecol Oncol 76 (1): 63-6, 2000.

  12. Long HJ 3rd, Bundy BN, Grendys EC Jr, et al.: Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 23 (21): 4626-33, 2005.

Recurrent Cervical Cancer

No standard treatment is available for patients with recurrent cervical cancer that has spread beyond the confines of a radiation or surgical field. For locally recurrent disease, pelvic exenteration can lead to a 5-year survival rate of 32% to 62% in selected patients.[1][2] These patients are appropriate candidates for clinical trials testing drug combinations or new anticancer agents.

The Gynecologic Oncology Group (GOG) has reported on several randomized phase III trials, (GOG-0179 [NCT00003945], GOG-0240 [NCT00803062]) in this setting. Single-agent cisplatin administered intravenously at 50 mg/m² every 3 weeks was the most-used regimen to treat recurrent cervical cancer since it was initially introduced in the 1970s.[3][4]

Various combinations containing cisplatin [3][4] failed to reach their primary endpoint of improving survival, however, a doubling of the cisplatin dose-rate did improve survival. Combinations with paclitaxel and with ifosfamide improved response rates (RR), but they did so at a cost of much greater toxicity, especially with the latter drug. A survival advantage over cisplatin was obtained with the cisplatin + topotecan (CT) doublet [4] leading to approval of this indication for topotecan by the Food and Drug Administration. However, in this study, cisplatin underperformed because many patients had received this drug earlier as a radiosensitizer. (Refer to Stages IIA, IIB, III, and IVA for more information on chemoradiation and the drug cisplatin, in particular.). Therefore, cisplatin plus paclitaxel (CP) was chosen as the reference arm in GOG-0204 (NCT00064077).

The GOG has reported on sequential randomized trials dealing with chemotherapy for stage IVB, recurrent, or persistent cervical cancer.[4][5][6][7][8] In the initial trial, the primary endpoint of exceeding the survival observed with cisplatin alone was not reached. However, in these trials:

  • The ifosfamide + cisplatin combination was superior to cisplatin alone in the secondary endpoint of RR but at the cost of increased toxicity.
  • The paclitaxel + cisplatin (PC) combination, similarly, was superior in RR and progression-free survival (PFS), and its toxicity was similar to the single agent except in patients with GOG performance status 2 (scale: 0, asymptomatic–4, totally bedridden).
  • The CT doublet combination had a significant advantage in overall survival (OS) compared with cisplatin alone, but cisplatin alone underperformed in this trial because as many as 40% of the patients had already received cisplatin up front as a radiosensitizer.

GOG-0204 enrolled 513 patients, leading to an early closure because no one experimental arm was likely to significantly lower the hazard ratio of death relative to PC:1.15 (95% confidence interval [CI], 0.79–1.67) for vinorelbine + cisplatin (VC), 1.32 (95% CI, 0.91–1.92) for gemcitabine plus cisplatin (GC), and 1.27 (95% CI, 0.90–1.78) for CT. Trend in RR, PFS, and OS favored CT.[9][Level of evidence: 1iiA] The patients in the various arms of the study differed in the extent of neutropenia, infection, and alopecia that they experienced,[9] but none of the patients in the study arms differed in health-related quality of life during treatment.[10] However, there were more neurologic side effects for PC.

Standard treatment options:

  1. For recurrence in the pelvis following radical surgery, radiation therapy in combination with chemotherapy (fluorouracil with or without mitomycin) may cure 40% to 50% of patients.[11]
  2. Chemotherapy can be used for palliation. Tested drugs include the following:
    • Cisplatin (15%–25% RR).[5]
    • Ifosfamide (15%–30% RR).[12][13]
    • Paclitaxel (17% RR).[14]
    • Irinotecan (21% RR in patients previously treated with chemotherapy).[15]
    • Bevacizumab (11% RR, 24% survived progression free for at least 6 months; as seen in GOG-0227C [NCT00025233]).[16]
    • Ifosfamide + cisplatin.[6][17]
    • PC (46% RR).[18]
    • GC (41% RR).[19]
    • CT (27% RR).[4]
    • VC (30% RR).[20]

Treatment options under clinical evaluation:

  • New anticancer drugs in phase I and phase II 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 recurrent cervical 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. Alberts DS, Kronmal R, Baker LH, et al.: Phase II randomized trial of cisplatin chemotherapy regimens in the treatment of recurrent or metastatic squamous cell cancer of the cervix: a Southwest Oncology Group Study. J Clin Oncol 5 (11): 1791-5, 1987.

  2. Tumors of the cervix. In: Morrow CP, Curtin JP: Synopsis of Gynecologic Oncology. 5th ed. New York, NY: Churchill Livingstone, 1998, pp 107-151.

  3. Tewari KS, Monk BJ: Gynecologic oncology group trials of chemotherapy for metastatic and recurrent cervical cancer. Curr Oncol Rep 7 (6): 419-34, 2005.

  4. Long HJ 3rd, Bundy BN, Grendys EC Jr, et al.: Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol 23 (21): 4626-33, 2005.

  5. Thigpen JT, Blessing JA, DiSaia PJ, et al.: A randomized comparison of a rapid versus prolonged (24 hr) infusion of cisplatin in therapy of squamous cell carcinoma of the uterine cervix: a Gynecologic Oncology Group study. Gynecol Oncol 32 (2): 198-202, 1989.

  6. Omura GA, Blessing JA, Vaccarello L, et al.: Randomized trial of cisplatin versus cisplatin plus mitolactol versus cisplatin plus ifosfamide in advanced squamous carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 15 (1): 165-71, 1997.

  7. Moore DH, Blessing JA, McQuellon RP, et al.: Phase III study of cisplatin with or without paclitaxel in stage IVB, recurrent, or persistent squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 22 (15): 3113-9, 2004.

  8. Tewari KS, Monk BJ: Recent achievements and future developments in advanced and recurrent cervical cancer: trials of the Gynecologic Oncology Group. Semin Oncol 36 (2): 170-80, 2009.

  9. Monk BJ, Sill MW, McMeekin DS, et al.: Phase III trial of four cisplatin-containing doublet combinations in stage IVB, recurrent, or persistent cervical carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 27 (28): 4649-55, 2009.

  10. Cella D, Huang HQ, Monk BJ, et al.: Health-related quality of life outcomes associated with four cisplatin-based doublet chemotherapy regimens for stage IVB recurrent or persistent cervical cancer: a Gynecologic Oncology Group study. Gynecol Oncol 119 (3): 531-7, 2010.

  11. Thomas GM, Dembo AJ, Black B, et al.: Concurrent radiation and chemotherapy for carcinoma of the cervix recurrent after radical surgery. Gynecol Oncol 27 (3): 254-63, 1987.

  12. Coleman RE, Harper PG, Gallagher C, et al.: A phase II study of ifosfamide in advanced and relapsed carcinoma of the cervix. Cancer Chemother Pharmacol 18 (3): 280-3, 1986.

  13. Sutton GP, Blessing JA, McGuire WP, et al.: Phase II trial of ifosfamide and mesna in patients with advanced or recurrent squamous carcinoma of the cervix who had never received chemotherapy: a Gynecologic Oncology Group study. Am J Obstet Gynecol 168 (3 Pt 1): 805-7, 1993.

  14. McGuire WP, Blessing JA, Moore D, et al.: Paclitaxel has moderate activity in squamous cervix cancer. A Gynecologic Oncology Group study. J Clin Oncol 14 (3): 792-5, 1996.

  15. Verschraegen CF, Levy T, Kudelka AP, et al.: Phase II study of irinotecan in prior chemotherapy-treated squamous cell carcinoma of the cervix. J Clin Oncol 15 (2): 625-31, 1997.

  16. Monk BJ, Sill MW, Burger RA, et al.: Phase II trial of bevacizumab in the treatment of persistent or recurrent squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 27 (7): 1069-74, 2009.

  17. Buxton EJ, Meanwell CA, Hilton C, et al.: Combination bleomycin, ifosfamide, and cisplatin chemotherapy in cervical cancer. J Natl Cancer Inst 81 (5): 359-61, 1989.

  18. Rose PG, Blessing JA, Gershenson DM, et al.: Paclitaxel and cisplatin as first-line therapy in recurrent or advanced squamous cell carcinoma of the cervix: a gynecologic oncology group study. J Clin Oncol 17 (9): 2676-80, 1999.

  19. Burnett AF, Roman LD, Garcia AA, et al.: A phase II study of gemcitabine and cisplatin in patients with advanced, persistent, or recurrent squamous cell carcinoma of the cervix. Gynecol Oncol 76 (1): 63-6, 2000.

  20. Morris M, Blessing JA, Monk BJ, et al.: Phase II study of cisplatin and vinorelbine in squamous cell carcinoma of the cervix: a Gynecologic Oncology Group study. J Clin Oncol 22 (16): 3340-4, 2004.


This information is provided by the National Cancer Institute.

This information was last updated on May 15, 2013.


 
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