Patient information: Ovarian cancer diagnosis and staging

INTRODUCTION

Ovarian cancer is one of the deadliest cancers in women, in part because it is often detected at an advanced stage. It occurs most frequently in women who are between 40 and 65 years of age. The lifetime risk of developing ovarian cancer is 1.4 to 1.8 percent for women living in the United States [1].

There are several different types of cancer that can develop in the ovary; epithelial ovarian cancer (EOC) is the most common type and is the subject of this topic review. We will hereafter use the term ovarian cancer to refer to EOC.

This topic review discusses the diagnosis and staging of ovarian cancer. A separate topic review is available that discusses ovarian cancer treatment. (See "Patient information: Ovarian cancer treatment".)

RISK FACTORS

The following factors increase the risk of developing ovarian cancer:

• Being a white person
• Never being pregnant
• Early age of menarche (the onset of the menstrual periods) or late age of menopause
• Family history of ovarian, breast, or endometrial (uterine) cancer, particularly if the person inherits a specific type of genetic abnormality called a BRCA1 or BRCA2 mutation. (See "Patient information: Genetic testing for breast and ovarian cancer".)

• Family history of hereditary nonpolyposis colorectal cancer (HNPCC). Women in families with this trait have up to a 60 percent chance of endometrial cancer and a 10 to 12 percent chance of ovarian cancer [2].

SIGNS AND SYMPTOMS

During the early stages of ovarian cancer, symptoms are often vague and ill-defined. Symptoms may include pelvic or abdominal discomfort, bloating, difficulty eating or feeling full, increased abdominal size, or urinary symptoms (urgency and frequency).

In some women, ovarian cancer is initially suspected when a mass or lump is felt during a routine pelvic examination. However, a mass is not always detectable in the early stages of ovarian cancer. Even when a mass is detected, it does not necessarily mean that the woman has ovarian cancer. A number of other non-cancerous conditions can cause masses.

Because the initial symptoms are vague and nonspecific, the majority of women have advanced stage disease by the time the diagnosis is made. At this point, the woman may have more prominent symptoms such as abdominal distention (swelling), nausea, or a significant loss of appetite.

DIAGNOSIS

If ovarian cancer is suspected because of symptoms and/or an abnormal physical examination, imaging tests of the abdomen and pelvis (such as a CT scan or MRI scan) are usually recommended initially. Radiology tests such as these do not provide enough information by themselves to definitively diagnose ovarian cancer, although they may provide important information about the location and/or extent of a possible cancer.

The only way to diagnose ovarian cancer with certainty is with an exploratory operation. If abnormal tissue is found during the operation, a small piece can be removed (biopsied) by the surgeon so that it can be examined under a microscope to determine if cancer is present (see 'Exploratory laparotomy' below.

In rare cases where open exploratory surgery is not possible because the woman is in poor health or the disease is advanced, a procedure to explore the abdomen using a small incision and a laparoscope (called diagnostic laparoscopy) may be recommended. In other cases, a nonsurgical procedure that removes fluid from the abdomen or chest with a needle (called paracentesis or thoracentesis) is done to confirm the diagnosis before chemotherapy begins.

Tumor markers (CA 125) — Prior to surgery, most women who are suspected of having ovarian cancer undergo a blood test to measure the level of a protein tumor marker called CA 125. This marker is normally less than 35 U/mL. CA 125 levels are elevated (above 65 U/mL) in 80 percent of women with ovarian cancer, particularly in those with advanced stage disease (see below).

Measurement of levels of CA 125 in the blood may be useful in one of two ways:

• As a laboratory test that supports the diagnosis of ovarian cancer
• As a marker of the relative activity of an ovarian cancer during treatment

Measuring the CA 125 level before surgery provides a baseline value that can then be used to monitor the success of treatment if ovarian cancer is found.

The use of CA 125 as a screening test for ovarian cancer is discussed separately. (See "Patient information: Ovarian cancer screening".)

Initial surgery — A procedure called exploratory laparotomy is typically recommended for women who are suspected of having ovarian cancer. This surgery is most successful in accurately diagnosing and treating ovarian cancer when it is performed by a gynecologic oncologist, a physician who has had extensive training in the management of cancers of the female reproductive system. Reasons to consult with a gynecologic oncologist are listed in Table 2 (table 1).

Exploratory laparotomy — During the procedure, a vertical (up and down) abdominal incision is made and the surgeon examines the organs within the pelvis and abdomen for signs of cancer. Samples of tissue and fluid are taken from the following areas:

• Within the abdominal cavity (also called the peritoneal cavity)
• The ovary
• Neighboring lymph nodes
• Other abdominal organs
• The omentum (the apron of fat that covers and connects the organs of the abdomen and pelvis)

While still in the operating room, the surgeon sends the tissues for microscopic examination by a pathologist, a physician who has specialized training in the examination of tissues. The pathologist examines the tissue samples during the surgery (called frozen section analysis), and then immediately notifies the surgeon as to whether definite signs of cancer are present. A more thorough examination of the fluid and tissue samples is performed after the surgery is completed (called permanent section analysis) to ensure that the initial diagnosis was correct.

If the pathologist finds evidence of ovarian cancer on frozen section analysis, the surgeon will then attempt to remove as much of the cancerous tissue as possible. This procedure is termed "debulking" or cytoreduction, and is an important first step in the treatment of ovarian cancer. Treatment outcomes are best in women whose debulking surgery removes all visible tumor (termed optimal debulking). Having the surgical procedure performed by a gynecologic oncologist provides the best chance for optimal debulking.

In most cases, the uterus, both fallopian tubes, and both ovaries are also removed (picture 1). If the cancer has spread to other organs, those organs, or affected portions of them, may be removed as well.

However, if a young woman wished to preserve her ability to bear children in the future, it may be possible to leave the uterus, one fallopian tube, and one ovary in place. This would only be possible if these structures seem to be unaffected by the cancer. The surgeon and patient should discuss this option before the operation is undertaken.

Minimally invasive procedure — In some patients, a less invasive procedure called exploratory laparoscopy may be performed. In this procedure, a flexible tube (a laparoscope) is inserted through a small incision in the abdomen. The laparoscope has a camera that the surgeon uses to visualize the contents of the abdomen and pelvis. This less invasive approach may be chosen for a young woman with a mass that is unlikely to be an ovarian cancer.

However, an open laparotomy is generally preferred because it allows the surgeon to more easily and completely visualize the abdominal contents and remove any suspicious masses.

STAGING

Based upon the findings during exploratory surgery, the tumor is formally "staged" according to the size, extent, and location of the cancer. Accurate staging during surgery is very important in determining a woman's long-term outcome (prognosis) and choosing the appropriate treatment regimen after surgery.

The stage of an ovarian cancer is defined by a Roman numeral designation between I and IV, and subdivided by the letters A, B, and C. The criteria used to define these individual stages are well described and widely accepted and used throughout the world (table 2).

In general, the stages I, II, III, and IV refer to the location of tumor involvement, while the subdivisions A, B, and C define the extent of tumor involvement. A higher stage of disease indicates more extensive tumor involvement. Worldwide, 23 to 33 percent of women have stage I disease at diagnosis, 9 to 13 percent of women have stage II, 46 to 47 percent have stage III, and 12 to 16 percent have stage IV [3,4].

Early stage cancer — Stage I and II disease are considered early stage ovarian cancer (table 2):

• In stage IA and IB disease, the cancer is limited to one or both or ovaries, and the capsule or membrane covering the ovaries has not been broken by the cancer's growth
• In stage IC disease, the capsule of either ovary may have ruptured or there may be signs suggesting that cancer cells have begun to spread within the pelvis (ie, there are cancerous cells in the fluid taken from the peritoneal cavity during surgery)
• In stage II disease, other pelvic organs such as the uterus or fallopian tubes are involved with the tumor, and there may be early signs that the cancer has spread beyond the pelvis.

Advanced stage disease

• In stage III disease, the cancer is confined to the abdomen and the abdominal lymph nodes (table 2).
• In stage IV disease, the cancer has spread to distant sites such as the liver or lungs (table 2).

Recommendations for postsurgical treatment vary according to disease stage. While a course of chemotherapy is recommended after surgery for all women with stage III or IV ovarian cancer, it may or may not be recommended for women who have stage I or II disease. (See "Patient information: Ovarian cancer treatment".)

PROGNOSIS

A number of factors influence the success of treatment for ovarian cancer. Treatment tends to be more successful when the cancer is diagnosed at an early stage, and in younger women (below the age of 67). One of the most important factors influencing the outcome of treatment is the amount of tumor that remains after the initial surgery (ie, the success of the initial debulking procedure). This is the reason that the surgeon aims to remove as much of the cancerous tissue as possible during the initial surgery. As noted above, this is most likely when the surgeon performing the debulking procedure is a gynecologic oncology specialist.

Complete response — At the end of treatment (both surgery and chemotherapy), a patient is considered to have a "complete response" if the physical examination is normal, there is no evidence of cancer on imaging studies (such as a CT scan), and the blood levels of CA 125 are normal. However, even when all of these criteria are met, small, sometimes microscopic amounts of residual cancer (ie, not visible on imaging studies) can still be present.

In some women, a second surgical exploration (termed a second-look laparotomy) may be performed to more conclusively evaluate the response to treatment. However, it is unclear whether the findings at second-look surgery influence later treatment and prognosis. For this reason, the benefit of second look surgery is controversial and it is not routinely recommended for all women.

Recurrence — Even women who have a complete response to initial therapy (as determined by physical examination, imaging studies, and/or second look surgery) can have a recurrence of ovarian cancer at a later time. The likelihood of a tumor recurrence is highest in women with more advanced stage disease at diagnosis, particularly if the initial debulking surgery was unable to remove all visible tumor. Signs of recurrent ovarian cancer include new symptoms (eg, abdominal bloating, back pain), a rising blood level of CA 125, or new findings on a follow-up CT scan. Further treatment may not be recommended immediately if the CA 125 level is slowly rising, there are no new symptoms, and a CT scan shows no new abnormalities that could indicate a disease recurrence.

TREATMENT

The treatment of ovarian cancer is discussed at length in a separate topic review. (See "Patient information: Ovarian cancer treatment".)

CLINICAL TRIALS

Progress in treating 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: Ovarian cancer treatment
Patient information: Genetic testing for breast and ovarian cancer
Patient information: Ovarian cancer screening

Professional Level Information:
Adjuvant therapy of early stage ovarian cancer
Epithelial ovarian cancer: Clinical manifestations, diagnostic evaluation, staging, and histopathology
Epithelial ovarian cancer: Initial surgical management
Epithelial ovarian cancer: Pathogenesis, epidemiology, and risk factors
Epithelial ovarian cancer: Second look surgery
First-line chemotherapy for epithelial ovarian cancer
Genetic counseling and psychosocial issues in women with an inherited predisposition to breast and ovarian cancer
Genetic testing for breast and ovarian cancer
Management of intraperitoneal chemotherapy for treatment of ovarian cancer
Management of ovarian cancer in pregnant women
Medical treatment for relapsed epithelial ovarian cancer
Options for women with a genetic predisposition to breast and ovarian cancer
Ovarian germ cell tumors: Pathology, clinical manifestations, and diagnosis
Ovarian tumors of low malignant potential
Overview of genetics in breast and ovarian cancer
Overview of the evaluation and management of adnexal masses
Risk reducing salpingo-oophorectomy in women at high risk of epithelial ovarian cancer
Screening for ovarian cancer
Surgery for recurrent epithelial ovarian cancer

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.

• People Living With Cancer: The official patient information

      website of the American Society of Clinical Oncology
       (www.cancer.net/portal/site/patient)

• The Women's Cancer Network

      (www.wcn.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)

• National Ovarian Cancer Coalition

      (www.ovarian.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)