Is CA125 (Cancer Antigen 125) used to measure endometrial cancer?

CA125 Is Not Recommended for Diagnosis of Endometrial Cancer

CA125 has no diagnostic value for endometrial cancer and should not be used for this purpose. 1

Diagnostic Approach for Endometrial Cancer

The British Journal of Cancer guidelines clearly establish that CA125 should not be used as a diagnostic tool for endometrial cancer. Instead, the following diagnostic algorithm should be followed:

1. First-line diagnostic tests:

   • Hysteroscopy
   • Transvaginal ultrasonography

2. Confirmatory testing:

   • Endometrial biopsy (Pipelle sampling)
   • Fractional curettage (95% diagnostic accuracy)

Limitations of CA125 in Endometrial Cancer

CA125 has significant limitations when used for endometrial cancer:

• It has poor sensitivity (only 57% for advanced disease at presentation) 2
• It produces false-positive elevations even in patients without disease 2
• It fails to predict recurrence in the absence of other clinical findings 2

Role of CA125 in Endometrial Cancer Management

While CA125 is not useful for diagnosis, it may have limited roles in other aspects of endometrial cancer management:

Potential prognostic value:

• Preoperative CA125 levels may correlate with:
  • Disease stage
  • Depth of myometrial invasion
  • Histologic grade
  • Cervical invasion
  • Peritoneal cytology
  • Lymph node status 3

Potential for disease monitoring:

• CA125 may predict extra-uterine extension at levels >35 U/ml 1
• However, it has limited utility in monitoring effects of adjuvant therapy 2

Emerging Alternatives to CA125

Recent research suggests better alternatives for endometrial cancer detection:

• HE4 (Human Epididymal Secretory Protein E4):

  • Superior to CA125 in detecting recurrent disease (75% vs 54% detection rate) 4
  • Can detect recurrence approximately 126 days earlier than clinical confirmation 4
  • Particularly useful in high-risk endometrial cancer patients 4

• Combination approaches:

  • HE4 combined with CA125 shows improved diagnostic performance compared to either marker alone 5
  • Urine CA125 combined with transvaginal ultrasound-measured endometrial thickness shows promise as a non-invasive triage tool 6

Clinical Pitfalls to Avoid

1. Do not rely on CA125 alone for diagnosis - it has poor sensitivity and specificity for endometrial cancer
2. Avoid using CA125 as a screening tool - it will lead to false positives and unnecessary procedures
3. Do not delay definitive diagnostic procedures (hysteroscopy, biopsy) while waiting for CA125 results
4. Be aware that CA125 may be normal even in advanced disease - one study reported a patient who died of disseminated disease despite never having elevated CA125 2

In conclusion, while CA125 may have some utility in prognosis and monitoring, it should not be used as a primary diagnostic tool for endometrial cancer. Clinicians should rely on established diagnostic methods like hysteroscopy, transvaginal ultrasound, and histological examination through biopsy.