What are the common markers for ovarian cancer?

Markers of Ovarian Cancer

Primary Tumor Marker: CA-125

CA-125 is the most important and widely used tumor marker for ovarian cancer, and should be measured before surgery and before starting chemotherapy in all patients with suspected ovarian cancer. 1, 2

Clinical Performance of CA-125

• CA-125 has a specificity of 98.5% in women over 50 years old when using a threshold of 35 U/mL, making it highly reliable for this population 1, 2
• CA-125 is elevated in approximately 80-90% of serous carcinomas (both low and high grade), which represent the majority of ovarian cancers 1
• Critical limitation: CA-125 detects only 50% of stage I ovarian cancers, so a normal level does not exclude early-stage disease 1, 2
• The true-positive rate increases to approximately 80% with stage II or greater disease 2

Monitoring and Follow-Up Uses

• CA-125 should be measured before each of the six cycles of chemotherapy and one month after the last cycle to monitor treatment response 1
• Serial CA-125 monitoring during follow-up visits is recommended for patients with initially elevated levels 2
• A progressively elevated CA-125 level over time, even within the normal range, should prompt further evaluation as it may indicate malignancy 1

Alternative Markers When CA-125 is Not Elevated

When CA-125 is not elevated, other markers should be measured, especially in mucinous or endometrioid tumors. 1

CA 19-9

• CA 19-9 should be measured when CA-125 is normal, particularly in clear cell tumors, teratomas, and mucinous tumors 1

Germ Cell Tumor Markers

In young women (particularly those under 35 years), additional markers must be measured to exclude germ cell tumors: 3, 1

• Alpha-fetoprotein (AFP) 3, 1
• Beta-human chorionic gonadotropin (beta-hCG) 3, 1

Markers NOT Recommended for Early Detection

HE4 and other emerging markers (mesothelin, B7-H4, DcR3, spondin-2) do not increase early enough to be useful in detecting early-stage ovarian cancer. 3, 1

Multi-Marker Panels Not Recommended for Screening

• The OVA1 test (using 5 markers: transthyretin, apolipoprotein A1, transferrin, beta-2 microglobulin, and CA-125) should NOT be used as a screening tool according to the Society of Gynecologic Oncologists and FDA 3, 1
• The OvaSure test (using 6 biomarkers: leptin, prolactin, osteopontin, insulin-like growth factor II, macrophage inhibitory factor, and CA-125) requires additional validation before use outside clinical trials 3

Critical Interpretation Caveats

CA-125 results must be interpreted in conjunction with clinical, imaging, and histological findings, as false positives occur in multiple benign conditions: 1

• Endometriosis 1
• Adenomyosis 1
• Pelvic inflammatory disease 1
• Benign ovarian cysts 1

Diagnostic Utility by Clinical Context

• CA-125 has little value for detecting early ovarian cancer due to lack of sensitivity for stage I disease and lack of specificity 4
• Preoperative CA-125 levels in postmenopausal women may aid differentiation of benign and malignant pelvic masses 4
• A high CA-125/CEA ratio can help differentiate ovarian from gastrointestinal primary tumors 2

No Effective Screening Test Available

Currently, no effective and sensitive screening test for ovarian cancer is available, and none is recommended by NCCN or any major organization. 3

• The PLCO trial found that screening with transvaginal ultrasonography and CA-125 did not decrease mortality from ovarian cancer 3
• False-positive screening results led to serious complications in some women 3