Ovarian Cancer Screening
Close surveillance or screening for cancer uses tests on a routine basis to identify cancer early on, at its most treatable stage. Surveillance doesn’t prevent cancer; however, catching cancer early improves a person’s odds of survival.
Ovarian cancer is particularly difficult to detect. Hidden deep in the abdominal cavity, ovaries are difficult to view or feel; abnormalities are not always found early. Even with the most rigorous surveillance, ovarian cancer is often detected only in its advanced stage. Even when detected early, the disease often requires aggressive treatment such as chemotherapy.
Surveillance recommendations for screening high-risk women for ovarian cancer differ from recommendations for the general population. In women with BRCA mutations or other hereditary risk factors, ovarian cancer tends to occur at a younger age and the lifetime risk is higher than in the general population. Therefore, screening tests that might not be appropriate for women of average risk for cancer may be recommended for those in the high-risk category. As further research is completed on surveillance for ovarian cancer in high-risk women, screening recommendations will probably change. For these reasons, it is important to consult with health care experts who are familiar with the standards of care and risk management in high-risk women.
The National Comprehensive Cancer Network (NCCN) is a consortium of cancer centers with experts in management of hereditary cancer. Each year, the NCCN updates their risk management guidelines for people with hereditary risk for cancer, based on the latest research. Current NCCN guidelines, which dictate the standard of care for cancer surveillance in high-risk patients, include:
- Concurrent transvaginal ultrasound with color doppler
- pelvic exam
every 6 months starting at age 30-35 or 5-10 yrs earlier than the earliest age of first diagnosis in the family, and preferably day 1-10 of the menstrual cycle for premenopausal women.
Scientists use the following criteria when considering the utility of a screening test:
- Sensitivity (true positives):
the probability of a positive test among those who have the disease.
If two women in a group of 100 have cancer, for example, a highly sensitive test would find positive results in both women.
- Specificity (true negatives):
the probability of a negative test among those who do not have the disease .
If only two women in the group of 100 have cancer, but 10 falsely test positive, the test is not very specific.
The ideal test is both sensitive and specific. If someone tests positive, they likely have the disease. If they test negative they likely don’t. It is difficult to develop a test that is highly sensitive and highly specific. Usually one quality is compromised at the expense of another.
CA125 is a protein in the blood that is sometimes elevated in women with ovarian cancer. The CA125 blood test is used to follow up women who have already been diagnosed with ovarian cancer, in order to monitor response to treatment and to look for recurrence of the cancer. Some researchers have looked at CA125 to detect ovarian cancer in women with ovarian abnormalities or in women who are at high risk for ovarian cancer. The test is considered neither sensitive nor specific for finding ovarian cancers in high-risk women. However, some studies found the test, particularly in combination with transvaginal ultrasound, might detect some ovarian cancers before symptoms appear. In a recent small study which looked at surveillance in high-risk women, CA125 and transvaginal ultrasound identified six cases of advanced ovarian cancer. The authors concluded that ovarian cancer surveillance was ineffective in this population. Research from a large study on ovarian screening known as GOG 199 found that premenopausal women have higher normal CA125 than postmenopausal women. Based on this, the reference ranges for normal CA125 in premenopausal women may change, making the test less likely to produce false positives.
Another study which reviewed published research on ovarian cancer detected through screening concluded that high grade serous ovarian cancer (the type of cancer that usually develops in mutation carriers) is more likely to be diagnosed at advanced rather than early stage, even if found during screening. Current NCCN guidelines recommend CA125 be performed every 6 months. Ongoing studies are looking at whether measuring CA125 every 3 months in high-risk women improves the sensitivity and specificity of the test.
Ultrasound uses special sound wave equipment to examine internal structures such as the ovaries. Transvaginal ultrasound uses a small probe inserted into the vagina to look for abnormalities of the ovaries, tubes and uterus.
One large study reviewed transvaginal ultrasound as a screening for ovarian cancer in women over age 50 or high-risk women over age 30. In this study 90 women underwent exploratory laparotomy (exploratory surgery of the abdominal organs) based on findings on the ultrasound. Of those 90 women, six had ovarian cancer: five were found at stage 1, the most treatable stage. In this study, none of the women with ovarian cancer had an elevated CA 125 test, a blood test sometimes elevated with ovarian cancer. A larger and more recent study examined ultrasound screening for early detection of ovarian cancer in high-risk women. In this study most ovarian cancers found were diagnosed at stage III, a more advanced stage. Further, all these women had normal scans in the previous year. The authors of the second study concluded that ultrasound was of limited value for finding ovarian cancer at an early stage. A study which reviewed published research on ovarian cancer detected through screening concluded that high grade serous ovarian cancer (the type of cancer that usually develops in mutation carriers) is more likely to be diagnosed at advanced rather than early stage, even if found during screening. Although transvaginal ultrasound doesn’t have a high sensitivity or specificity, it is still recommended by many experts for screening those women who are not prepared to undergo prophylactic oophorectomy (removal of healthy ovaries to reduce the risk of developing ovarian cancer).
A pelvic exam is an internal vaginal exam by a health care provider to look and feel for abnormalities of the reproductive system. The pelvic exam should include a rectovaginal exam—the health care provider feels the ovaries by inserting a gloved and lubricated finger in the rectum and another finger of the same hand into the vagina at the same time, while pressing on the abdomen. As uncomfortable as it may sound, the rectovaginal exam should not be painful; it provides the best possible way for a health care provider to actually feel the position, size and shape of the ovaries. Although a pelvic exam might pick up an abnormality that could indicate cancer, it is not considered a sensitive or a specific test for ovarian cancer. Nevertheless, the pelvic exam should be part of a thorough exam for all adult women, and is recommended by NCCN and other experts for surveillance in high-risk women.
Biomarkers are substances such as proteins or other molecules which might indicate the presence or progression of a disease such as ovarian cancer. CA125 is an example of a biomarker for ovarian cancer. Scientists are looking for other biomarkers that might lead to more sensitive and specific tests for ovarian cancer. Several possible substances have been identified. Lysophosphatidic acid (LPA) is a substance identified in a recent study as a possible biomarker for ovarian cancer.
The science of proteomics identifies the thousands of proteins produced by the body, and how they function in health and illnesses such as cancer. Advances in proteomics are improving our capability of identifying smaller proteins and identifying a large number of proteins at one time in a mass analysis. Some researchers are searching for “protein patterns” that might indicate specific cancers more accurately. One small study looking at a proteomic test showed high sensitivity and specificity for detecting ovarian cancer. A more recent study found blood tests which tested for three proteins in addition to CA125 improved the sensitivity of the CA125 for screening for ovarian cancer. Research is continues to determine whether proteomic testing can lead to an accurate test to detect early-stage ovarian cancer.
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