Diagnostic performance of CA125 in the detection of ovarian cancer

Diagnostic performance of CA125 in the detection of ovarian cancer

Cancer Antigen 125 (CA125), also referred to as Carbohydrate Antigen 125

• CA125 is a high molecular weight mucinous glycoprotein found on the surface of ovarian cancer cells. This antigen is then shed and quantified in serum samples of ovarian cancer patients (1,2,3)
  • upper limit is 35 U/mL
  • serum CA125 levels are elevated in 50% of early-stage tumours, which are mostly type I ovarian cancers and 92% of advanced-stage tumours, which are mostly type II ovarian cancers
    • measurement is not very sensitive in the early phases of ovarian cancer (only reported to be elevated in 23 to 50% of stage I cases) (2)
    • elevated serum CA125 levels may be observed in other physiological or pathological conditions (menstruation, pregnancy, endometriosis, inflammatory diseases of the peritoneum) (2)
    • due to the low incidence of ovarian cancer, screening average-risk women with CA125 results in a considerable number of false positives
    • sensitivity of multimodal screening with serial CA125 measurements and transvaginal ultrasound based on risk was 85.8% at a specificity of 99.8%
• cohort study of over 50,000 women who underwent CA125 testing in English general practice (3)
  • 10.1% of those with a CA125 at or above the conventional cutoff (35 U/ml) were diagnosed with ovarian cancer
    
    
  • 12.3% with a CA125 >= 25 U/ml were diagnosed with a different cancer
    
    
  • almost a third of women aged >= 50 years with a CA125 >=35 U/ml were diagnosed with some form of cancer
    
    
  • a CA125 level of 53 U/ml equated to an overall ovarian cancer probability of 3%
    • marked variation was noted between women of different ages, with the 3% probability reached at lower CA125 levels in 70-year-old women than younger or older women
    • ovarian cancer probability of 3% equated to a value of 104 U/ml in 40-year-old women and 32 U/ml in 70-year-old women

Ovarian cancer can be classified into:

• Type I ovarian tumours (1):
  • Endometrioid, clear cell, low-grade serous carcinomas (LGSC), mucinous carcinomas, seromucous carcinomas, malignant Brenner tumours
  • Type I tumours develop in a stepwise manner from borderline tumours and are usually diagnosed in earlier stages (I, II)
• Type II ovarian tumours (1):
  • high-grade serous carcinoma (HGSC), carcinosarcoma, undifferentiated carcinoma
  • majority of type II tumours are known to develop de novo from the fallopian tubes in the form of microscopic serous tubal intraepithelial carcinomas (STIC). Such tumours are usually diagnosed in advanced stages (III, IV) and have distinct morphologic and molecular genetic features compared to type I tumours
• a review suggests that type II ovarian cancers are usually diagnosed in advanced stages and have significantly higher CA125 levels than type I tumours (1)

Reference:

• Charkhchi P, Cybulski C, Gronwald J, Wong FO, Narod SA, Akbari MR. CA125 and Ovarian Cancer: A Comprehensive Review. Cancers (Basel). 2020 Dec 11;12(12):3730. doi:10.3390/cancers12123730.
• Dochez V et al. Biomarkers and algorithms for diagnosis of ovarian cancer: CA125, HE4, RMI and ROMA, a review. J Ovarian Res 12, 28 (2019). https://doi.org/10.1186/s1304-019-0503-7
• Funston G, Hamilton W, Abel G, Crosbie EJ, Rous B, Walter FM. The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study. PLoS Med. 2020 Oct 28;17(10):e1003295.