Cancer Antigen 125 (CA-125)

oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

This is a surface antigen on a high molecular weight glycoprotein recognised by a monoclonal antibody (produced using an ovarian cancer cell line). It is most useful as a marker for non-mucinous ovarian epithelial cancer, and indeed is present in up to 80% of cases of advanced ovarian cancer - but is often negative earlier in the disease.

 

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Malignant disease

  • Ovarian cancer
  • Uterine cancer
  • Other intra-abdominal cancers (pancreas, stomach, colon, rectum)[1] and metastases from other sites (eg breast).

Non-malignant conditions

  • Benign ovarian tumour (eg Meigs' syndrome).[2]
  • Endometriosis.
  • Pelvic inflammatory disease/salpingitis.
  • Pregnancy and menstruation.
  • Leiomyoma.
  • Ascites - eg liver disease (cirrhosis) and renal failure.
  • Diverticulosis.
  • Pleural and pericardial disease.
  • Pancreatitis.
  • Heart failure.[3]

Elevated CA-125 is associated with many conditions - listed above. However, currently it is mainly used when ovarian cancer is suspected and for monitoring after treatment.

Monitoring known patients with ovarian cancer for relapse

Three studies have looked at the correlation of CA-125 in patients treated for ovarian cancer, who subsequently underwent a second staging operation to look for any persisting disease. Combining the results, the CA-125 has a sensitivity of 55% and a specificity of 96%, giving a positive predictive value of around 96% and a negative predictive value of 53%.[4] Thus, in patients with known ovarian cancer, a rising CA-125 is a good indicator of residual disease but a normal result will be a false negative about half the time in this group (not a good indicator of small volume disease).

Investigation of female patients with a pelvic mass

CA-125 can be used in the assessment of patients presenting with a pelvic mass. An elevated result has a sensitivity of 72% and specificity of 78% for ovarian cancer (positive predictive value of 72% and a negative predictive value of 78%). If ultrasound results are combined with menopausal status, a risk of malignancy index (RMI) can be calculated. Using a cut-off level of 200 to indicate malignancy, the RMI gave a sensitivity of 90%, specificity of 89%, positive predictive value of 96%, and negative predictive value of 78% in this group.[5]

If a serum CA-125 level is raised in a premenopausal patient, but less than 200 units/mL, further investigation may be required to exclude or treat differential diagnoses.[6] A level of more than 200 units/mL should prompt referral to a gynaecologist.

CA-125 level is not necessary when a simple ovarian cyst has been diagnosed by ultrasound.

Screening for ovarian cancer

The relatively low prevalence of ovarian cancer means that the positive predictive value of CA-125 as a screening test is extremely low. CA-125 is unreliable in differentiating benign from malignant ovarian masses in premenopausal women because of the increased rate of false positives and reduced specificity.[6] This is because an elevated CA-125 level is also found in fibroids, endometriosis, adenomyosis and pelvic infection. When levels are elevated, serial monitoring can be helpful, as rapidly rising levels are more likely to be associated with malignancy than high levels which are static.

CA-125 is being evaluated as a screening tool for patients at high risk of ovarian cancer, in combination with other tests.[7] The UK Familial Ovarian Cancer Screening Study (UKFOCSS) is recruiting women with strong family histories or mutations in BRCA1 or BRCA2, to be screened with transvaginal ultrasound scan of the ovaries combined with a CA-125 level, three times a year.[8] A second study, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) study has finished recruiting, and compares annual CA-125 screening with transvaginal ultrasound against no screening or just annual vaginal ultrasound.[9]

Further reading & references

  1. Epithelial ovarian cancer, Scottish Intercollegiate Guidelines Network - SIGN (2003)
  2. Lacey JV Jr, Greene MH, Buys SS, et al; Ovarian cancer screening in women with a family history of breast or ovarian cancer. Obstet Gynecol. 2006 Nov;108(5):1176-84.
  3. Vizzardi E, D'Aloia A, Pezzali N, et al; Long-Term Prognostic Value of CA 125 Serum Levels in Mild to Moderate Heart J Card Fail. 2012 Jan;18(1):68-73. Epub 2011 Nov 9.
  4. William M Rich, MD, CA-125, Gynecologic Oncology Associates
  5. Obeidat BR, Amarin ZO, Latimer JA, et al; Risk of malignancy index in the preoperative evaluation of pelvic masses. Int J Gynaecol Obstet. 2004 Jun;85(3):255-8.
  6. Management of Suspected Ovarian Masses in Premenopausal Women, Royal College of Obstetricians and Gynaecologists (December 2011)
  7. Jelovac D, Armstrong DK; Recent progress in the diagnosis and treatment of ovarian cancer. CA Cancer J Clin. 2011 May-Jun;61(3):183-203. Epub 2011 Apr 26.
  8. UK Familial Ovarian Cancer Screening Study
  9. Menon U, Gentry-Maharaj A, Hallett R, et al; Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS). Lancet Oncol. 2009 Mar 10.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Huw Thomas
Current Version:
Peer Reviewer:
Dr Hannah Gronow
Last Checked:
20/02/2012
Document ID:
3179 (v24)
© EMIS