Ovarian Cancer Screening — CA-125 and Beyond

CA-125 is a biomarker that can be elevated in ovarian cancer, yet ovarian cancer remains one of the most challenging cancers to detect early. Only 20% of all ovarian cancer cases are discovered in early stages, as the disease often goes undetected until it has spread within the pelvis and abdomen. This difficulty in early detection contributes to ovarian cancer being the fifth leading cause of cancer deaths among women and causing more deaths than any other gynecologic cancer.

CA-125 has been the most promising biomarker for screening ovarian cancer; however, it still does not have an acceptable accuracy in population-based screening. While screening tools exist, including the CA-125 blood test, comprehensive health panels, and complete blood counts, understanding their limitations and appropriate use is crucial for making informed decisions about ovarian cancer screening, particularly for women with elevated risk factors.

The exact cause of ovarian cancer is not fully understood, but several risk factors may increase the likelihood of developing this condition. Age is a significant factor, with ovarian cancer being most common in women ages 50 to 60 years, and the average age of an ovarian cancer diagnosis is 63.

Inherited gene mutations play a role in a small percentage of cases, with genes known to increase risk including breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2), which also increase breast cancer risk. Other gene mutations associated with Lynch syndrome may also contribute to ovarian cancer risk. Family history is another important factor, with those having ovarian cancer in a mother, aunt, grandmother, or sister being at higher risk. Additional factors that may influence risk include never having children and never taking birth control, as well as estrogen hormone replacement therapy, especially with long-term use and in large doses.

Healthcare providers use CA-125 testing for early detection of ovarian cancer in people who are at high risk, which could include factors such as immediate family members having ovarian cancer or genetic mutations that increase cancer risk. A CA-125 test isn't useful for people with no symptoms or risk factors.

When symptoms are caused by ovarian cancer, they tend to be persistent and a change from normal, occurring more often or being more severe. If symptoms occur more than 12 times a month, it's important to see a healthcare provider. If you experience symptoms on a daily basis for more than a few weeks, it's advisable to see a healthcare provider. Testing may also be appropriate for those with increased risk factors for ovarian cancer, particularly those with genetic mutations or strong family history of the disease.

The reference range for CA-125 is 0-35 units/mL (0-35 kU/L), with levels over 35 U/mL potentially indicating the presence of cancer or other conditions. However, interpreting CA-125 results requires careful consideration of multiple factors. CA-125 levels can be normal even with cancer present (false negative), or elevated without cancer (false positive).

In about 20 percent of advanced stage disease cases and 50 percent of early-stage disease cases, CA-125 is not elevated even when ovarian cancer is present. False positives can occur due to benign conditions like fibroids, endometriosis, or even pregnancy. The CA-125 test is most reliable in postmenopausal women who have a mass. A CBC alone cannot determine if someone has ovarian cancer, as additional tests like imaging studies and specialized blood tests are needed for confirmation. Any abnormal results should always be interpreted by a healthcare provider in the context of symptoms, medical history, and other diagnostic tests.

While there's no guaranteed way to prevent ovarian cancer, certain lifestyle factors may help reduce risk. Using oral contraceptives is one way that many women can reduce their risk of developing ovarian cancer, and oral contraceptives also seem to reduce this risk for women with BRCA1 and BRCA2 mutations. Women who have been pregnant and carried to term before age 26 have a lower risk than those who have not, with risk decreasing with each full-term pregnancy, while women who have their first pregnancy after age 35 or never carried a pregnancy to term have higher risk.

For women at high risk due to genetic factors, healthcare providers may recommend risk-reducing surgery to remove ovaries and tubes before they become cancerous. Genetic testing may be recommended for those unsure about their mutation status. Regular communication with healthcare providers about family history and personal risk factors is essential for making informed decisions about screening and prevention strategies.