What conditions are associated with elevated Cancer Antigen 125 (CA125) levels?

Conditions Associated with Elevated CA-125 Levels

CA-125 is elevated in multiple conditions including ovarian cancer, endometriosis, pelvic inflammatory disease, benign ovarian cysts, cirrhosis, peritonitis, and conditions causing pleural effusion or ascites. 1, 2

Malignant Conditions

• Ovarian Cancer:

  • Most common malignant cause of CA-125 elevation
  • Elevated in approximately 85% of advanced ovarian cancer cases
  • Only elevated in about 50% of early-stage (FIGO stage I) ovarian cancer 1, 2
  • Can reach extremely high levels (up to 10,000 units/mL) in some cases 3

• Other Gynecological Cancers:

  • Endometrial cancer (detection rate of 15%) 2

• Non-Gynecological Malignancies:

  • Breast cancer
  • Lung cancer
  • Colon cancer
  • Pancreatic cancer 2

Benign Gynecological Conditions

• Endometriosis:

  • 54% of patients with advanced endometriosis (stage III or IV) have CA-125 levels >35 U/mL 4
  • Can cause extremely high elevations (case report of 1243 units/mL) 5

• Other Benign Gynecological Conditions:

  • Benign ovarian cysts
  • Tubo-ovarian abscess
  • Leiomyomata uteri (fibroids) - elevated in 14% of cases 4
  • Pelvic inflammatory disease - elevated in 5% of cases 4
  • Ovarian hyperstimulation syndrome 6, 3

Physiological Conditions

• Normal Female Reproductive Events:
  • Menstruation
  • Pregnancy 6, 3

Non-Gynecological Conditions

• Abdominal/Peritoneal Conditions:

  • Peritonitis
  • Cirrhosis
  • Ascites
  • Inflammatory bowel disease (including Crohn's disease) 5

• Thoracic Conditions:

  • Conditions causing pleural effusion 3

• Other Conditions:

  • Renal failure
  • Heart failure
  • Hepatitis 1

Clinical Significance and Interpretation

• CA-125 is not specific for any single condition and should be interpreted in the context of the complete clinical picture 2

• The pattern of elevation is important:

  • Progressive elevation over time is more concerning for malignancy
  • Single elevated values may be due to benign conditions 2

• CA-125 has higher specificity in postmenopausal women compared to premenopausal women 2

• No professional organization recommends CA-125 alone for screening average-risk women for ovarian cancer due to limited sensitivity and specificity 2

• Referral to a gynecologic oncologist is recommended for CA-125 levels greater than 200 units/mL 2

Diagnostic Approach

• For suspected ovarian cancer, CA-125 should be combined with imaging (transvaginal ultrasound) 1, 2

• For mucinous ovarian tumors, measuring serum CEA and CA 19-9 in addition to CA-125 helps distinguish primary ovarian tumors from gastrointestinal metastases 1

• The combination of CA-125 with other biomarkers like Human Epididymis Protein 4 (HE4) improves diagnostic accuracy 2