Ovarian Cancer Ultrasound Screening

What is ovarian cancer?

Ovarian cancer is a disease in which cells in the ovaries multiply and grow abnormally. The ovaries are almond-sized female reproductive organs that produce eggs, as well as the female hormones estrogen and progesterone. Women usually have two ovaries located in the pelvis — one on each side of the uterus. If the genes that control cell growth in the ovaries no longer work properly, the cell divides uncontrollably and may form a tumor.

What are the different types of ovarian cancer?

Ovarian cancer can develop in different types of cells that make up the ovaries. These include:

• Surface epithelial cells, which cover the outer surface of the ovaries

• Germ cells, which ultimately form eggs

• Stromal cells, which help hold the ovary together and release estrogen and progesterone

Ninety percent of ovarian tumors develop in the surface epithelial cells. Cancer in these cells often arises at the end of the fallopian tubes, which are located on each side of the uterus. The eggs travel through the fallopian tubes to the uterus. Cancer also can develop in the peritoneum, the tissue linking the wall and covering the organs of the abdomen. Ovarian, fallopian tube, and peritoneal cancer are basically treated the same way.

Am I at risk for getting ovarian cancer?

Ovarian cancer affects 1 in 70 women across their lifetime and is the second most common type of gynecologic cancer in the United States. The most common risk factor is age. About two-thirds of all ovarian cancers are diagnosed in women between ages 50-75. Only 5 percent of ovarian cancers diagnosed occur in women under the age of 30.

Ovarian Cancer Screening

While the most common recognized risk factor associated with the disease is advancing age, other factors contributing to an increased risk of the disease include infertility, endometriosis (a condition in which tissue from the lining of the uterus grows outside of the uterus), and post-menopausal hormone replacement therapy. Additionally, some studies have suggested — but other studies have not confirmed — that use of assisted reproductive technologies such as in vitro fertilization may increase a woman’s risk of developing ovarian cancer. It is important to note, however, that these age-independent risk factors do not significantly increase a woman’s chances of developing ovarian cancer, elevating a woman’s risk level no more than two to three times higher than that of the general population.

Recommendations for ovarian cancer screening traditionally have been organized into one of two sets of guidelines — one for women at average risk and the other for women at increased risk. Now, with the identification of gene mutations that can increase a woman’s chances of developing ovarian cancer, the set of guidelines for women at an increased risk has been subdivided into two groups, with recommendations for women with a clear inherited risk of developing ovarian cancer due to an identified genetic mutation differing from those for women with a family history of the disease. This concept of variable risk has been incorporated into Memorial Sloan Kettering’s current recommendations for ovarian cancer screening.

Ovarian Cancer Risk Types

Women with a risk level near that of the general population (relative risk less than three times the relative risk of the general population)

This category includes women with any of the following:

• A history of breast cancer diagnosed at age 41 or older and a) no family history of breast or ovarian cancer or b) no Ashkenazi Jewish heritage (individuals of Eastern European Jewish descent from Eastern Europe).

• A history of infertility and/or use of assisted reproductive therapies, such as in vitro fertilization (IVF).

• A history of endometriosis (a condition in which tissue from the lining of the uterus grows outside of the uterus).

• A history of hormone replacement use for the management of symptoms related to menopause.

Women with increased risk* (relative risk three to six times greater than that of the general population)

This category includes woman with any of the following:

• A first degree relative (mother, sister, or daughter) with ovarian cancer.

• A personal history of breast cancer prior to age 40.

• A personal history of breast cancer diagnosed prior to age 50, and one or more close relatives diagnosed with breast or ovarian cancer at any age.

• Two or more close relatives diagnosed with breast cancer prior to age 50 or with ovarian cancer diagnosed at any age.

• Ashkenazi Jewish heritage and a personal history of breast cancer prior to age 50.

• Ashkenazi Jewish heritage and a first- or second-degree relative diagnosed with breast cancer prior to age 50 or with ovarian cancer at any age.

* These estimates are obtained from studies in which genetic testing information was not available. For individuals who meet the family history criteria but have tested negative for a genetic mutation known to increase susceptibility to the disease, the risk of developing ovarian cancer may be substantially lower. These women should consult a medical professional for screening recommendations.

Women with inherited risk due to known genetic mutations (relative risk greater than six times that of the general population)

This category includes woman with any of the following:

• Presence of a BRCA1 or BRCA2 mutation. BRCA1 and BRCA2 are genes involved in cell growth, division, and repair of damage to DNA that occurs naturally during one’s lifetime. An altered, or mutated, BRCA1 or BRCA2 gene increases the likelihood that cancer will develop. The most common types of cancers associated with BRCA alterations are breast and ovarian cancer.

• Presence of a mismatch repair gene mutation associated with a hereditary cancer syndrome known as Hereditary Non-Polyposis Colon Cancer (HNPCC)/Lynch syndrome.

Mutations in the genes known to increase susceptibility to ovarian cancer likely account for a large proportion of the incremental risk among women with a family history of ovarian or breast cancer diagnosed before the age of 50. Preliminary evidence has suggested that women with a strong family history of breast cancer but no demonstrable mutation in BRCA1 or BRCA2 may not be at significantly increased risk of ovarian cancer. For this reason and due to the limitations of currently available ovarian cancer screening tests, which are described below, women in the increased risk category should consider genetic counseling and testing prior to initiating ovarian cancer screening or other ovarian cancer risk-reduction strategies.

Ovarian Cancer Screening Tests

A number of tests have been evaluated as potential methods of screening for ovarian cancer. Screening tests with the greatest amount of clinical test data supporting their use include transvaginal ultrasound and the blood test for the serum marker CA-125. (Serum markers are substances in the blood that can be detected in blood tests.) Less information is available regarding a number of other serum markers, used alone or in combination. A newer test based on proteomics, a method which involves the evaluation of patterns of dozens to hundreds of low molecular weight proteins simultaneously, has also been recently proposed.

CA-125

CA-125 is a protein produced by more than 90 percent of advanced epithelial ovarian cancers. (Epithelial ovarian cancer is the most common form of the disease.) As a result, the CA-125 protein has become the most evaluated serum marker for ovarian cancer screening. In the largest study to date, 22,000 post-menopausal women at average risk of ovarian cancer were randomly chosen to receive either annual CA-125 tests or their usual gynecologic care. In this study, women with ovarian cancer detected by the CA-125 tests had improved survival compared to women diagnosed with ovarian cancer who were assigned to their usual care. While these results were promising, there was no difference between the two groups in the number of deaths due to ovarian cancer. Additionally, although 8,732 women were screened, only six ovarian cancers were detected, with three of these being at an advanced stage.

Other studies have suggested that CA-125 also appears to be elevated in two to three percent of normal post-menopausal women. Given this fact and the relatively low annual incidence of ovarian cancer, screening using the CA-125 test has not been effective enough to warrant its widespread use. For ovarian cancer to be detected in one additional woman using CA-125 as the primary screening method, another 100 to 150 women would have to receive evaluation and approximately 30 diagnostic operations be performed.

To improve the utility of CA-125 measurements for ovarian cancer screening, a method has been proposed that focuses on the change in CA-125 concentration in the bloodstream over time, as opposed to relying on the absolute value. This approach is being used in an ongoing study in Great Britain, in which 200,000 women will be randomly assigned to receive screening with CA-125, screening with transvaginal ultrasound, or their usual care. Results from this study are expected in 2012.

Transvaginal Ultrasound

A number of imaging methods have been evaluated for possible use in ovarian cancer screening. Transvaginal ultrasound has consistently proven to be the most promising imaging method for routine screening of ovarian cancer.

In the largest study to date evaluating ultrasound as a screening method for ovarian cancer, 14,469 women, most of whom were at average risk for ovarian cancer, were monitored using annual transvaginal ultrasounds. Promisingly, 11 of 17 cancers detected by transvaginal ultrasound screening were diagnosed at the earliest stage of the disease, known as stage I. Critics, however, have pointed out than only two of the 11 stage I cancers detected by transvaginal ultrasound were high grade (meaning that the cancer cells have an aggressive growth rate), compared to all six of the advanced stage cancers.

Serum CA-125 in Combination with Transvaginal Ultrasound

Several studies have evaluated the combined use of transvaginal ultrasound and CA-125. These studies have suggested that the combination of these tests result in a higher sensitivity for ovarian cancer detection, but at the cost of an increased rate of false positive results. In an ongoing prostate, lung, colorectal, and ovarian cancer screening trial, 28,816 women were randomly chosen to receive annual transvaginal ultrasound and CA-125 testing. An additional 39,000 women were randomly assigned to a control group in which they received only their usual gynecologic care. The positive predictive values for an abnormal test were one percent for transvaginal ultrasound and 3.7 percent for CA-125. When both were abnormal, this value increased to 23.5 percent. Final results, including impact of screening on ovarian cancer mortality, are expected in 2015.

Our Ovarian Cancer Screening Guidelines

Women with a risk near that of the general population (relative risk less than three times greater than that of the general public)

• Ovarian cancer screening is not recommended. An annual gynecologic examination with pelvic examination is recommended for preventive healthcare.

Women with increased risk (relative risk of three to six times greater than that of the general public)

• There is no clear evidence to suggest that ovarian cancer screening with currently available methods will result in a decrease in the number of deaths from ovarian cancer. If, after careful consideration of risks and benefits, ovarian cancer screening with serum markers such as CA-125 and/or transvaginal ultrasound is to be pursued, it is recommended that such screening be done within the framework of research studies to evaluate the efficacy of this approach.

Genetic counseling may also be helpful for women in this group to better clarify the risk of ovarian and related cancers.

Women with inherited risk (relative risk more than six times greater than that of the general public)

• While it is not clear that ovarian cancer screening will result in a decrease in the number of deaths in women at inherited risk, those who have mutations in ovarian cancer susceptibility genes should undergo ovarian cancer screening using a combination of transvaginal ultrasound and CA-125 testing. For women with mutations in BRCA1 or the mismatch repair genes, MLH1, MSH2, and MSH6, this screening should generally begin between ages 30 and 35. For women with mutations in BRCA2, ovarian cancer screening should be initiated between ages 35 and 40.

Given the limitations of ovarian cancer screening, including the substantial risks of both false positive and false negative results, risk-reducing salpingo-oophorectomy (a surgical procedure that removes a woman’s ovaries and fallopian tubes) should be considered upon conclusion of childbearing by women with documented inherited predispositions.

What are the symptoms of ovarian cancer?

Ovarian cancer rarely has noticeable symptoms when it is in its earliest stages. As the cancer progresses, subtle signs begin to appear, but you might not notice them right away, or they may be blamed on other common conditions.

The symptoms of ovarian cancer include:

• abdominal bloating or swelling

• pain in the abdomen or pelvis

• difficulty eating, or feeling full quickly

• lack of appetite

• feeling an urgent need to urinate

• needing to urinate frequently

• change in bowel habits (constipation or diarrhea)

• change in menstrual periods

• vaginal bleeding between periods

• back pain

• weight gain or loss

Although the symptoms of ovarian cancer may be vague, particularly in the early stages, they are usually fairly constant and represent a change from how you normally feel. Symptoms also worsen as the cancer progresses. If you experience any of these symptoms every day, or almost every day, for more than two to three weeks, speak with your doctor and specifically ask if you could have ovarian cancer. If it is ovarian cancer, the earlier we can diagnose it, the better the chances for an effective treatment.

How do you test for ovarian cancer?

For most women, there is no effective way to screen for cancer in the ovaries, peritoneum, or fallopian tubes. Current tests are not reliable or accurate enough, especially for early-stage disease — and our experts have concluded that the risks generally outweigh potential benefits. This is one reason why it’s important for all women to be aware of the risk factors for this illness, and to stay sensitive to changes that might be symptoms of it.

How is ovarian cancer diagnosed?

To check for ovarian cancer, your doctor will likely perform a pelvic exam to feel for lumps or changes in and around the ovaries, and order additional tests if you’ve been experiencing persistent abdominal bloating, discomfort, or other symptoms, or if you have risk factors for this cancer. If you do have ovarian cancer, surgery can give us crucial information about your diagnosis, from the type of tumor you have to its stage (if it has spread and if so, how far). This information helps your team of specialists decide which treatments are best for you.

What are the treatments for ovarian cancer?

Surgery is the main treatment for ovarian cancer, regardless of whether the disease is early or advanced. The type of surgery you receive depends on several factors, including the type and stage of your cancer, your general health, and whether you plan on having children in the future. Our experts recommend that most women undergo chemotherapy as a preventative measure after surgery.