What cancers are associated with elevated Cancer Antigen 125 (CA 125) levels?

Cancers Associated with Elevated CA-125 Levels

Elevated CA-125 levels are primarily associated with epithelial ovarian cancer (present in ~85% of advanced cases), but can also be found in multiple non-gynecological malignancies and benign conditions. 1

Primary Gynecological Cancers with Elevated CA-125

• Epithelial Ovarian Cancer (EOC): The most common cancer associated with CA-125 elevation
  • Present in approximately 85% of patients with advanced disease 1
  • Only elevated in about 50% of early-stage (FIGO stage I) cases 1
  • All histological subtypes can be antigen positive 2
  • Subtypes include:
    • High-grade serous carcinoma (70% of cases) 1
    • Endometrioid carcinoma (10%) 1
    • Clear cell carcinoma (6-10%) 1
    • Low-grade serous carcinoma (5%) 1
    • Mucinous carcinoma (3-4%) 1

Non-Gynecological Cancers with Elevated CA-125

• Gastrointestinal Malignancies:

  • Pancreatic cancer (elevated in approximately 45% of cases) 3
  • Colorectal cancer 1, 4
  • Gastric cancer 4

• Other Non-Gynecological Cancers:

  • Breast cancer 1, 4
  • Lung cancer 1, 4
  • Non-ovarian adenocarcinomas (elevated in approximately 41% of cases) 2

Clinical Significance and Limitations

• Diagnostic Value:

  • CA-125 is not specific for ovarian cancer and has limited value as a screening test 5, 4
  • The marker aids diagnosis but should be interpreted alongside imaging and clinical findings 1
  • Elevated CA-125 levels correlate with tumor burden in ovarian cancer 2

• Monitoring Value:

  • Useful for monitoring treatment response in established ovarian cancer 5, 4
  • Changes in CA-125 levels reflect disease progression or regression in approximately 91% of cases 2
  • Rising levels can precede clinical detection of relapse by a median of 3.5 months 6

• Differential Diagnosis:

  • For mucinous ovarian tumors, measuring CEA and CA 19-9 in addition to CA-125 helps distinguish primary ovarian tumors from gastrointestinal metastases 1
  • A CA-125/CEA ratio of >25 favors ovarian origin over gastrointestinal origin 1

Benign Conditions with Elevated CA-125

• Gynecological Conditions:

  • Endometriosis 1, 5
  • Pelvic inflammatory disease 1, 5
  • Ovarian cysts 1
  • Menstruation 5
  • Pregnancy 5

• Non-Gynecological Conditions:

  • Peritonitis 5
  • Pancreatitis 3
  • Cirrhosis 1
  • Benign hepatocellular diseases 3
  • Any condition causing pleural effusion or ascites 5

Pitfalls and Caveats

• CA-125 levels can be markedly elevated (>1000 U/mL) even in benign conditions, limiting its value in differentiating benign from malignant disease 5
• Normal CA-125 levels do not exclude the presence of ovarian cancer, particularly in early-stage disease 4, 6
• CA-125 cannot reliably detect small tumor nodules (<2 cm) 6
• The marker's lack of specificity makes it unsuitable for population-based screening 5, 4