What tumor marker should I order for an ovarian mass?

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Tumor Marker for Ovarian Mass

Order CA-125 as the primary tumor marker for evaluating an ovarian mass, as it is the most widely used and clinically validated marker for epithelial ovarian cancer. 1

Primary Recommendation: CA-125

  • CA-125 should be measured before surgery in all patients with suspected ovarian cancer, with a specificity of 98.5% in women over 50 years old when using a threshold of 35 U/mL 1

  • CA-125 is elevated in approximately 80-90% of serous carcinomas (the most common type of epithelial ovarian cancer) 1

  • The combination of CA-125 with ultrasound imaging provides better diagnostic accuracy than either test alone for differentiating benign from malignant ovarian masses 2

Critical Limitations of CA-125

  • CA-125 only detects 50% of stage I ovarian cancers, so a normal level does not exclude early malignancy 1

  • False-positive elevations occur commonly with benign conditions including endometriosis, adenomyosis, pelvic inflammatory disease, benign ovarian cysts, and cirrhosis 1, 3

  • CA-125 performed worse than ultrasound alone in distinguishing benign from malignant lesions and only improved specificity for lesions already suspected to be malignant on imaging 2

Additional Markers When CA-125 is Not Elevated

  • Measure CA 19-9 when CA-125 is normal, particularly if imaging suggests clear cell, mucinous, or endometrioid tumors 1

  • These tumor subtypes may not produce elevated CA-125 levels, making alternative markers essential for proper evaluation 1

Special Populations Requiring Additional Markers

  • In young women (particularly under age 35), also measure alpha-fetoprotein (AFP) and beta-hCG to exclude germ cell tumors 1

  • Germ cell tumors represent a distinct category of ovarian malignancy that requires different tumor markers for detection 1

Markers NOT Recommended

  • Do not order OVA1 or multimarker panels as screening tools, as they are not recommended by the Society of Gynecologic Oncologists or FDA for this purpose 1

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

Clinical Integration

  • Always interpret CA-125 results in conjunction with imaging findings (transvaginal ultrasound with color Doppler is the primary imaging modality) 2

  • A progressively elevated CA-125 level over time, even within the normal range, should prompt further evaluation as it may indicate malignancy 1

  • When CA-125 is elevated with imaging showing an indeterminate mass, MRI with IV contrast is the next best step for further characterization 2

Common Pitfalls to Avoid

  • Do not rely on CA-125 alone to make surgical decisions, as it lacks sufficient sensitivity for early disease 4

  • Do not test CA-125 in patients with ascites from any cause (especially cirrhosis), as it is universally elevated and nonspecific in this setting 5, 3

  • Do not assume a normal CA-125 excludes ovarian cancer, particularly in premenopausal women or early-stage disease 1, 4

References

Guideline

Tumor Markers for Ovarian Cancer

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

CA125 in ovarian cancer: European Group on Tumor Markers guidelines for clinical use.

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society, 2005

Guideline

Cancers Associated with Elevated CA-125 Levels

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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