What are the recommended tumor markers for ovarian cancer screening in women of different age groups, including younger age, middle age, and older age?

From the Guidelines

Currently, there is no recommended routine screening for ovarian cancer using tumor markers in asymptomatic women at any age. The most studied marker is CA-125, but it lacks sufficient sensitivity and specificity for general population screening 1. For high-risk women (those with BRCA1/2 mutations or strong family history), some clinicians may use CA-125 along with transvaginal ultrasound starting around age 30-35, but this approach is not proven to reduce mortality 1. For women at average risk, no tumor marker screening is recommended at any age. Other markers like HE4, OVA1, and ROMA have been studied but are primarily used for evaluating suspicious pelvic masses rather than screening 1. The lack of effective screening methods explains why ovarian cancer is often diagnosed at advanced stages. Instead of tumor marker screening, women should be aware of persistent symptoms like bloating, pelvic pain, difficulty eating, and frequent urination, and those with high genetic risk should discuss risk-reduction strategies with their healthcare providers. Some key points to consider include:

• The UK Collaborative Trial of Ovarian Cancer Screening showed that multimodality screening is more effective at detecting early-stage cancer, but a significant mortality reduction was not observed 1.
• The Risk of Ovarian Cancer Algorithm (ROCA) has been studied as a potential screening tool, but its effectiveness in reducing mortality is unknown 1.
• The US Preventive Services Task Force recommends against routine screening for ovarian cancer in asymptomatic women at any age 1. In summary, the use of tumor markers for ovarian cancer screening is not recommended for asymptomatic women at any age, and women should be aware of persistent symptoms and discuss risk-reduction strategies with their healthcare providers if they have a high genetic risk.

From the Research

Tumor Markers for Ovarian Cancer Screening

The following tumor markers are recommended for ovarian cancer screening in women of different age groups:

• CA125: a widely used marker, but its effectiveness remains debated due to low positive predictive values and high false positive rates 2, 3
• HE4: a more specific marker for ovarian cancer, particularly when combined with CA125 and menopausal status in the Risk of Ovarian Malignancy Algorithm (ROMA) 4, 5
• ROMA: a algorithm that combines CA125, HE4, and menopausal status to predict the risk of malignancy, showing good diagnostic performance in postmenopausal women 5

Age-Specific Recommendations

• Younger age: no specific recommendations are available, but HE4 and ROMA may be useful in combination with other markers 4, 5
• Middle age: CA125 and HE4 may be used in combination, with ROMA showing good diagnostic performance in premenopausal women 5
• Older age: ROMA is recommended, as it shows the best diagnostic performance in postmenopausal women 5

Screening Strategies

• Multimodal screening: earlier detection and significant downstaging of ovarian cancer have been demonstrated with multimodal screening, but no mortality benefit has been shown 6
• Risk-stratified CA125 screening: incorporating CA125 trajectories, trajectory-specific progression, and transvaginal ultrasound may improve the effectiveness of ovarian cancer screening 3
• Population testing: an emerging novel strategy to identify women at high risk who can benefit from ovarian cancer prevention 6