Patient information: Cervical cancer treatment; early stage cancer

CERVICAL CANCER OVERVIEW

More than 10,000 American women develop cancer of the uterine cervix (cervical cancer) each year. However, this number has been decreasing steadily over the past 50 years as a result of the widespread use of Pap tests (also called cervical cytology screening). Cervical cancer is a treatable condition and there is a good chance of cure if it is found and treated in the early stages. (See "Patient information: Cervical cancer screening".)

This article discusses the diagnosis and treatment of women with early stage cervical cancer. A separate article discusses the treatment of early stage cervical cancer in women who want to become pregnant in the future. (See "Patient information: Cervical cancer treatment for women who desire future pregnancy; early stage cancer".)

CERVICAL CANCER SYMPTOMS

Typically, cervical cancers develop slowly over a period of several years. It may not cause any symptoms initially or it may cause abnormal vaginal discharge or bleeding. This can include bleeding between menstrual periods, bleeding after sexual intercourse, or bleeding after menopause. This bleeding may be no more than a spot of blood.

Abnormal bleeding can also be caused by a number of other conditions that may or may not be related to cancer. Any woman who develops abnormal vaginal bleeding should consult a healthcare provider.

CERVICAL CANCER DIAGNOSIS AND STAGING

Cervical cancer is diagnosed with a cervical biopsy. A biopsy involves removing a small piece of abnormal appearing tissue. This is done either because the clinician sees an abnormal area on the cervix, or because of an abnormal Pap test. The biopsy is performed during an office visit using a procedure called colposcopy. The colposcope (similar to a large magnifying lens) magnifies the cervix (picture 1). This allows the clinician to better see the location, extent, and degree of very small abnormalities that may not be visible with the naked eye alone.

The tissue obtained during the biopsy is analyzed under a microscope to determine if cervical cancer cells are present. Sometimes the small colposcopy-directed biopsies are not sufficient to diagnose cervical cancer and a larger biopsy, called cervical conization, is needed (figure 1).

If a biopsy shows the presence of a cervical cancer, a doctor who specializes in cancers of the female reproductive system (called a gynecologic oncologist) should be consulted. A gynecologic oncologist has received specialized training in the techniques needed to diagnose and treat cervical cancer as well as other gynecologic cancers.

FIGO staging system — Once a diagnosis of cervical cancer is made, the next step in the evaluation is to assess the "stage" of the cancer. Staging is a system that describes the size of the cancer and any signs of spread. For all cancers, including cervical cancer, treatment and prognosis depend upon the tumor stage.

For cervical cancers, the stage is based upon the size of the cancer and how deeply it has invaded into the tissues surrounding the cervix, whether the vagina, side walls of the pelvis, or local lymph nodes are involved, and whether the cancer has spread to other organs (metastasized).

The International Federation of Gynecologists and Obstetricians (FIGO) system is the most commonly used staging system for cervical cancer (table 1). This system classifies the extent of disease involvement as stage 0 through IV (four), with IV being the most advanced stage [1].

The FIGO staging system is mainly based upon the results of physical examination, which includes a complete pelvic (internal) examination of the cervix, uterus, and ovaries. Other procedures may also be performed to evaluate how far the cancer has invaded locally. Patients may be asked to undergo a chest x-ray or bone x-rays to detect distant spread to the lungs or bone.

Other imaging tests are often recommended to determine the best treatment approach, but the results do typically not change the FIGO stage. These include computed tomography (CT scan), magnetic resonance imaging (MRI), and/or positron emission tomography (PET scan).

CERVICAL CANCER TREATMENT OPTIONS

There are several options for treatment of early stage (stage IA, IB, and some small IIA tumors) cervical cancer. The optimal treatment depends upon the woman's age and her childbearing plans, the stage of the cancer, whether underlying medical conditions are present, and the physician's and patient's preferences.

The most common treatment for early stage cervical cancers is radical hysterectomy (surgical removal of the cervix and uterus). The alternative is radiation therapy, which is usually given in combination with chemotherapy. Patients with the earliest stage cervical cancers (stage IA1) may also be treated by cervical conization or simple hysterectomy alone. (See "Patient information: Treatment of abnormal Pap smears".) for information about conization and (see "Patient information: Abdominal hysterectomy" for information about simple hysterectomy).

Future pregnancies are not possible after radical hysterectomy or radiation therapy. Some women who wish to preserve their ability to carry a pregnancy after treatment may be eligible for less aggressive forms of treatment (fertility preserving therapies). These involve partial or complete removal of the cervix while leaving the uterus in place. Women who are not eligible for less aggressive treatment may have options that allow them to have a biologically related child. These issues are discussed separately. (See "Patient information: Cervical cancer treatment for women who desire future pregnancy; early stage cancer".)

Radical hysterectomy — Radical hysterectomy is a surgical procedure that removes the uterus and cervix with adjacent tissues and a portion of the vagina (figure 2). The surgery is done in the operating room after the woman receives anesthesia. Removal of the ovaries is not a necessary part of a radical hysterectomy. A woman's preference to leave or remove the ovaries is usually discussed before surgery. (See "Patient information: Abdominal hysterectomy", section on "Removal of ovaries" for more information about removal of the ovaries.)

The surgery is usually performed by removing the uterus and cervix through a vertical or horizontal incision in the abdomen (figure 2). Alternately, surgery may be done laparoscopically using a small telescope and several small incisions in the abdomen. With laparoscopic surgery, the uterus and cervix are removed through the vagina. The surgical approach depends upon the surgeon's preference and experience and the woman's anatomy. Most women will also undergo a lymphadenectomy (removal of the pelvic and para-aortic lymph nodes, (figure 3), depending upon the stage of the cancer and what is found during surgery.

The time required for radical hysterectomy and pelvic lymphadenectomy is approximately 2.5 to four hours; more time may be required if lymph nodes in other areas are removed or if complications such as bleeding or injury to surrounding organs occurs. Most women remain in the hospital for two to three days after surgery.

If abnormal or cancerous cells are found at the margins (edges) of the tissue or in the lymph nodes that are removed, or if the tumor has other features that increase the risk that the cancer will recur, further (adjuvant) treatment is recommended. This generally includes both radiation therapy and chemotherapy.

Radiation therapy — Radiation therapy (RT) refers to the exposure of a tumor to high-energy x-rays in order to slow or stop its growth. Exposure to x-rays damages cells. Unlike normal cells, cancer cells cannot repair the damage caused by exposure to x-rays, particularly when it is administered over several days. This prevents the cells from further growth, and causes them to eventually die.

There are two ways to deliver RT for cervical cancer: brachytherapy or external beam radiation therapy (EBRT).

Brachytherapy — Brachytherapy is a form of localized RT in which the source of the radiation is within the patient (internal irradiation). This allows the delivery of high doses of radiation to the area where cancer cells are most likely to be found, hopefully minimizing the effects of radiation on healthy tissues.

In most cases, a radiation applicator is temporarily inserted through the vagina into the cervix and uterus. Then, the radiation source is placed (or "afterloaded") into the applicator and left in place internally for a period of time. The treatment is traditionally accomplished using a radiation source that delivers the radiation at a low dose rate (LDR), which requires that the woman remain in the hospital for two to three nights. A newer technique delivers the radiation at a high dose rate (HDR). The main advantage of HDR is that it is completed within several minutes, and can be performed as an outpatient. Studies that compare HDR to LDR therapy are ongoing.

External beam radiation therapy (EBRT) — During EBRT, the radiation beam is generated by a machine that is outside the patient. The radiation is delivered to the patient, who is usually lying on a table underneath or in front of the machine. The high energy beams are targeted to the pelvic area.

Exposure to the beam typically takes only a few seconds (similar to having an x-ray). In general, treatment is repeated five days per week for approximately five to six weeks. Treatment cannot be given over a shorter period because the higher daily doses would cause too many side effects. Unless medically indicated, treatment should not be interrupted or extended beyond the projected time frame because changing the schedule or stopping temporarily could reduce the chance of curing the cancer.

Brachytherapy alone is adequate treatment for the earliest stage IA tumors, but EBRT is generally added to brachytherapy to improve the outcomes in women who have with more advanced disease [2].

Chemotherapy — Most women who undergo EBRT for cervical cancer also receive chemotherapy during the radiation therapy (an approach termed chemoradiotherapy). Chemotherapy drugs are medicines that stop or slow the growth of cancer cells. In general, these drugs work by interfering with the ability of rapidly growing cells (like cancer cells) to divide or multiply.

Chemotherapy also has the ability to enhance the damaging effect of radiation therapy on cervical cancer cells; when chemotherapy drugs are used in this manner, they are referred to as "radiation sensitizers". The chemotherapy is usually given once per week through a vein during the course of EBRT.

It is not clear if there is a benefit of chemoradiotherapy (compared to radiotherapy alone) for all women with early stage cervical cancer. Studies of women with predominantly locally advanced cervical cancer have demonstrated that there is a lower risk of recurrence and a better survival when RT is given along with chemotherapy compared to when RT is given alone [3]. That benefit was greater in trials that included a higher proportion of patients with stage I and II disease [4]. These results may not apply to women with smaller early stage cervical cancers, although most gynecologic oncologists recommend that chemotherapy be administered when EBRT is used, regardless of the stage.

CERVICAL CANCER FOLLOW UP

After cervical cancer treatment, periodic follow-up testing and examination are recommended. Guidelines from the National Comprehensive Cancer Network (NCCN) suggest the following [5]:

• Physical examination every three months for one year, every four months for one year, every six months for three years, and then annually. This usually involves a physical examination and Pap test (cervical cytology).
• Annual chest x-ray; there are few data to support the benefit of annual chest x-rays and many doctors do not recommend them.
• Other radiographic studies, including CT or PET scan, are recommended if needed

LONG-TERM OUTLOOK

Psychosocial function — The women and families affected by cervical cancer commonly experience distress as they worry about their short and long-term health and risk of recurrence. In some cases, this distress continues for many years after treatment ends.

Communication between the woman, her family, and her healthcare team is a vital part of the treatment process. Many women benefit from bringing a family member or friend to physician visits; this person can help the woman to understand her options, ask important questions, take notes, and feel supported.

A variety of support options are available, both during and following cervical cancer treatment, including individual counseling, support groups, and internet-based discussion groups. A list of reputable groups is available below (see 'Where to get more information' below.

Sexual function — Vaginal changes after cervical cancer treatment may include shortening, narrowing, and decreased vaginal lubrication. These physical changes impact sexual satisfaction because they may lead to pain during intercourse, lack of interest in sex, difficulty having an orgasm, and decreased frequency of sexual activity. If the vagina is severely narrowed, use of vaginal dilators may help.

Using a vaginal moisturizer or lubricant during intercourse can relieve some of these bothersome symptoms. Counseling for sexual and/or psychological difficulties may also be helpful. (See "Patient information: Sexual problems in women".)

Cure — Each patient with cancer is different, and it is difficult to predict what an individual woman can expect in the future. The chance of cure is high for most early stage cervical cancers. When discussing chances of cure, it is important to remember that these numbers represent averages, and do not necessarily predict what will happen to you.

The survival rates for women who undergo standard treatment for stage IA1 cervical cancer are excellent. At five years after diagnosis, more than 98 percent of women are alive. This means that 2 percent of women died, although the cause of death was not necessarily related to the cancer.

For stage IA2, more than 95 percent of women who undergo standard treatment are alive at five years after diagnosis. For stage IB1 disease, approximately 88 percent of women are alive at five years after diagnosis. Again, some of these women died as a result of their cancer, while others died of other causes (eg, accidents, heart disease).

CLINICAL TRIALS

Progress in treating cervical cancer requires that better treatments be identified through clinical trials, which are conducted all over the world. A clinical trial is a carefully controlled way to study the effectiveness of new treatments or new combinations of known therapies. Ask for more information about clinical trials, or read about clinical trials at:

       www.cancer.gov/clinical_trials/learning/

       www.cancer.gov/clinical_trials/

       http://clinicaltrials.gov/

WHERE TO GET MORE INFORMATION

Your healthcare provider is the best source of information for questions and concerns related to your medical problem. Because no two people are exactly alike and recommendations can vary from one person to another, it is important to seek guidance from a provider who is familiar with your individual situation.

This discussion will be updated as needed every four months on our web site (www.uptodate.com/patients). Additional topics as well as selected discussions written for healthcare professionals are also available for those who would like more detailed information.

Some of the most pertinent include:

Patient Level Information:
Patient information: Management of atypical squamous cells (ASC-US and ASC-H) and low grade cervical squamous intraepithelial lesions (LSIL)
Patient information: Management of high grade cervical squamous intraepithelial lesions (HSIL) and glandular abnormalities (AGC)
Patient information: Cervical cancer screening
Patient information: Cervical cancer treatment for women who desire future pregnancy; early stage cancer
Patient information: Treatment of abnormal Pap smears
Patient information: Abdominal hysterectomy
Patient information: Sexual problems in women

Professional Level Information:
Cervical intraepithelial neoplasia: Definition, incidence, and pathogenesis
Clinical trials of human papillomavirus vaccines
Epidemiology of human papillomavirus infections
Invasive cervical cancer: Epidemiology, clinical features, and diagnosis
Invasive cervical cancer: Management of early stage disease (FIGO IA, IB1, nonbulky IIA) and special circumstances
Invasive cervical cancer: Management of stages IB2, bulky IIA, and locally advanced disease
Invasive cervical cancer: Staging
Management of adenocarcinoma and neuroendocrine carcinoma of the cervix
Management of disseminated or recurrent cervical cancer
Overview of AIDS-defining malignancies in HIV infection
Overview of preventive medicine in adults
Preinvasive and invasive cervical neoplasia in HIV-infected women
Radical hysterectomy
Recommendations for the use of human papillomavirus vaccines
Virology of human papillomavirus infections and the link to cancer
Patient information: Management of atypical squamous cells (ASC-US and ASC-H) and low grade cervical squamous intraepithelial lesions (LSIL)
Patient information: Management of high grade cervical squamous intraepithelial lesions (HSIL) and glandular abnormalities (AGC)

A number of web sites have information about medical problems and treatments, although it can be difficult to know which sites are reputable. Information provided by the National Institutes of Health, national medical societies and some other well-established organizations are often reliable sources of information, although the frequency with which they are updated is variable.

• American Society of Clinical Oncology

      (www.cancer.net/portal/site/patient)

• The Gynecologic Cancer Foundation

       (www.thegcf.org)

• National Comprehensive Cancer Network

      (www.nccn.com)

• Gynecologic Oncology Group

      (www.gog.org/gynecologiccancerinformation.html)

• National Cancer Institute

       1-800-4-CANCER
       (www.cancer.gov)

• American Cancer Society

       1-800-ACS-2345
      (www.cancer.org)

• The National Cervical Cancer Coalition

      (www.ncc-online.org)

Patient Support — There are a number of online forums where patients can find information and support from other people with similar conditions.

• About.com Cancer Forum

      (http://cancer.about.com/forum)

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