Does CA125 (Cancer Antigen 125) serve as a marker for endometrial cancer?

CA125 as a Marker for Endometrial Cancer

CA125 is not recommended as a routine diagnostic marker for endometrial cancer, but it may have value in specific clinical scenarios such as monitoring advanced disease, serous histology, or when elevated before treatment. 1

Diagnostic Value of CA125 in Endometrial Cancer

• CA125 has poor diagnostic value for endometrial cancer detection 1
• In asymptomatic patients with endometrial cancer, CA125 levels account for only 15% of recurrence detections 1
• The sensitivity/detection rate of CA125 for endometrial cancer recurrence is significantly lower (15%) compared to its use in ovarian cancer (62-74%) 1

When CA125 May Be Useful

CA125 testing may be appropriate in select patients with:

1. Advanced stage disease (stage III/IV)
2. Serous histologic subtype
3. Patients who had elevated CA125 levels before initial treatment 1
4. Predicting extra-uterine extension at levels >35 U/ml 1

CA125 in Relation to Disease Characteristics

• CA125 correlates with prognosis, but its clinical benefit to patient outcomes remains uncertain 1
• Recent research shows CA125 >35 kU/L is associated with:
  • Higher disease stage
  • Lymph node metastases
  • Worse overall survival, disease-specific survival, and progression-free survival 2
  • Relative risk of 2.50 for stage III/IV disease 2

Molecular Classification Context

• CA125 levels vary by molecular subtype of endometrial cancer:
  • POLEmut tumors have the lowest median CA125 levels
  • p53abn tumors have the highest proportion of abnormal CA125 levels 2
• When combined with molecular classification, CA125 provides additional prognostic information that can guide management 2

Comparison with Other Markers

• HE4 (Human Epididymal Secretory Protein E4) demonstrates higher sensitivity (58%), positive predictive value (60%), and negative predictive value (67%) than CA125 alone for endometrial cancer detection 3
• The combination of HE4, CA125, CA724, and CA19-9 has shown improved diagnostic value compared to any single marker 3
• Recent research has explored urine CA125 as a potential non-invasive diagnostic tool, showing promising results when combined with transvaginal ultrasound measurements 4

Clinical Pitfalls

• Elevated CA125 levels can occur due to other conditions or previous radiotherapy, leading to false positives 1
• Normal CA125 levels may provide false reassurance in postmenopausal women with intermediate or high-risk lesions 1
• Despite positive tissue staining for CA125 in most endometrial cancer specimens (89.3%), only 21.4% of patients show elevated serum levels, suggesting mechanisms that prevent CA125 from entering circulation 5

Conclusion

For endometrial cancer management, clinicians should rely primarily on established diagnostic methods like hysteroscopy, transvaginal ultrasonography, and biopsy for diagnosis 1. CA125 should be reserved for specific clinical scenarios rather than routine screening or diagnosis.