Ovarian Cancer Screening: CA-125 and Beyond

Ovarian cancer remains one of the most difficult cancers to detect early. Only 20% of cases are discovered at early stages, as the disease frequently goes undetected until it has spread beyond the ovaries. This diagnostic challenge contributes to ovarian cancer being the fifth leading cause of cancer deaths among women and the deadliest of all gynecologic cancers.

CA-125, a protein that can be elevated in ovarian cancer, has been the most widely studied screening biomarker, but it does not yet achieve the accuracy needed for reliable population-wide 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 critical for informed decision-making, particularly for women with elevated risk factors.

The exact cause of ovarian cancer is not fully understood, but several risk factors have been identified. Age is a significant factor, with the condition most common in women between 50 and 60 years old and the average age at diagnosis being 63.

Inherited gene mutations contribute to a small percentage of cases. The BRCA1 and BRCA2 genes, also associated with elevated breast cancer risk, are the most well-known genetic risk factors. Mutations associated with Lynch syndrome may also increase ovarian cancer risk. Family history is another important consideration, with risk elevated for those who have a mother, aunt, grandmother, or sister with ovarian cancer. Additional factors that may influence risk include nulliparity (never having been pregnant), never having used oral contraceptives, and estrogen hormone replacement therapy, particularly with long-term use at higher doses.

Healthcare providers use CA-125 testing primarily for individuals at high risk for ovarian cancer, which may include those with immediate family members affected by the disease or those carrying genetic mutations that increase susceptibility. CA-125 testing is not considered useful for individuals without symptoms or risk factors.

When symptoms are caused by ovarian cancer, they tend to be persistent, represent a change from normal, and occur frequently. If symptoms such as bloating, pelvic pain, difficulty eating, or urinary urgency occur more than 12 times per month or daily for more than a few weeks, medical evaluation is advisable. Testing may also be appropriate for women with increased risk factors, particularly those with known genetic mutations or a strong family history of the disease.

The reference range for CA-125 is 0 to 35 U/mL, with levels above 35 U/mL potentially indicating cancer or other conditions. However, interpretation requires careful clinical judgment. CA-125 can be normal even when cancer is present (false negative) or elevated in the absence of cancer (false positive).

In approximately 20% of advanced-stage ovarian cancers and 50% of early-stage cases, CA-125 is not elevated despite the presence of disease. False positives can occur with benign conditions including fibroids, endometriosis, pelvic inflammatory disease, and pregnancy. The test is most reliable in postmenopausal women who have a pelvic mass. A CBC alone cannot determine ovarian cancer status; additional evaluation including imaging and sometimes specialized blood tests is needed for confirmation. All abnormal results should be interpreted by a healthcare provider in the context of symptoms, medical history, and other diagnostic findings.

While no guaranteed prevention method exists for ovarian cancer, certain factors may help reduce risk. Oral contraceptive use has been shown to reduce ovarian cancer risk, including in women with BRCA1 and BRCA2 mutations. Women who have carried a pregnancy to term before age 26 face lower risk than those who have not, with risk decreasing further with each additional full-term pregnancy. Conversely, first pregnancy after age 35 or never having carried a pregnancy to term is associated with higher risk.

For women at high risk due to genetic factors, healthcare providers may discuss risk-reducing surgery (removal of the ovaries and fallopian tubes) before cancer develops. Genetic testing can help clarify mutation status for those who are uncertain. Regular, open communication with healthcare providers about family history, genetic risk factors, and any persistent symptoms is essential for making well-informed screening and prevention decisions.