Cancer Antigen 125 CA 125
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Treatment of almost all medical conditions has been affected by the COVID-19 pandemic. NICE has issued rapid update guidelines in relation to many of these. This guidance is changing frequently. Please visit https://www.nice.org.uk/covid-19 to see if there is temporary guidance issued by NICE in relation to the management of this condition, which may vary from the information given below.
What is cancer antigen 125 (CA 125)?
Cancer antigen 125 (CA 125) 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.
Conditions which may cause elevated CA 125
- Ovarian cancer.
- Endometrial cancer.
- Fallopian tube cancer.
- Other intra-abdominal cancers (pancreatic cancer, stomach cancer, colorectal cancer) and metastases from other sites (eg, breast, lung).
- Benign ovarian tumours (eg, Meigs' syndrome).
- Pelvic inflammatory disease/salpingitis.
- Pregnancy and menstruation. (CA 125 can increase two- to three-fold during menstruation.)
- Leiomyoma, including fibroids.
- Ascites with non-malignant causes - eg, liver disease (cirrhosis).
- Pleural and pericardial disease.
- Heart failure .
Uses of CA 125
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.
Investigation of female patients with symptoms suggestive of ovarian cancer
CA 125 can be used in the assessment of patients presenting with a pelvic mass. It is, however, a nonspecific test, ie raised in other conditions, many of which are benign (see above).
The National Institute for Health and Care Excellence (NICE) recommends sequential testing of serum CA 125 followed by abdominopelvic ultrasonography if the serum CA 125 level is 35 IU/L or more. Women with clinical findings of ascites and a pelvic or abdominal mass should be referred urgently .
However CA 125 is nonspecific and raised in other conditions, and the level of CA 125 is only increased in 50% of stage 1 cancers .
There is also no universally agreed scoring system to triage women with suspected benign or malignant adnexal masses detected by ultrasonography at primary care level. Ovarian masses that are multilocular, bilateral, solid, or associated with ascites and metastasis are extremely suspicious and should prompt rapid referral.
Since NICE guidelines were published in 2011 advocating symptom-triggered testing of CA 125 leading to ultrasound scan where raised, studies have shown that cancers are not detected at an earlier stage but that it may increase the chance of complete tumour removal at surgery[3, 6, 7] .
See the separate Ovarian Cancer article for more details on symptoms, signs and early detection of this condition.
Monitoring known patients with ovarian cancer for relapse
A number of reviews have failed to identify survival advantage for the process of monitoring CA 125 in asymptomatic women after treatment[8, 9] . It has often traditionally been used to try to pick up relapse early but is currently not recommended .
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 . This is because an elevated CA 125 level is also found in so many other conditions. 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.
Large studies have evaluated CA 125 as a screening tool in combination with ultrasound scanning to detect ovarian cancer early but results so far have failed to demonstrate benefit . Therefore, it is not recommended outside research settings .
However, CA 125 is still being evaluated as a screening tool for patients at high risk of ovarian cancer, in combination with other tests. The UK Familial Ovarian Cancer Screening Study (UKFOCSS) recruited women over a number of years who had 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 regularly and continue to follow this up . A second study, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) study reports encouraging early results but further follow-up is awaited before conclusions can be reached .
Further reading and references
Moss EL, Moran A, Reynolds TM, et al; Views of general practitioners on the role of CA125 in primary care to diagnose ovarian cancer. BMC Womens Health. 2013 Feb 1913:8. doi: 10.1186/1472-6874-13-8.
Menon U, Griffin M, Gentry-Maharaj A; Ovarian cancer screening--current status, future directions. Gynecol Oncol. 2014 Feb132(2):490-5. doi: 10.1016/j.ygyno.2013.11.030. Epub 2013 Dec 3.
CA 125 (serum); Association for Clinical Biochemistry (ACB), 2012
Vizzardi E, D'Aloia A, Pezzali N, et al; Long-term prognostic value of CA 125 serum levels in mild to moderate heart failure patients. Heart J Card Fail. 2012 Jan18(1):68-73. Epub 2011 Nov 9.
Sundar S, Neal RD, Kehoe S; Diagnosis of ovarian cancer. BMJ. 2015 Sep 1351:h4443. doi: 10.1136/bmj.h4443.
Ovarian cancer - the recognition and initial management of ovarian cancer; NICE Clinical Guideline (April 2011)
Management of epithelial ovarian cancer; Scottish Intercollegiate Guidelines Network - SIGN (Nov 2013 - revised 2018)
Gilbert L, Basso O, Sampalis J, et al; Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project. Lancet Oncol. 2012 Mar13(3):285-91. doi: 10.1016/S1470-2045(11)70333-3. Epub 2012 Jan 17.
Andersen MR, Lowe KA, Goff BA; Value of symptom-triggered diagnostic evaluation for ovarian cancer. Obstet Gynecol. 2014 Jan123(1):73-9. doi: 10.1097/AOG.0000000000000051.
Clarke T, Galaal K, Bryant A, et al; Evaluation of follow-up strategies for patients with epithelial ovarian cancer following completion of primary treatment. Cochrane Database Syst Rev. 2014 Sep 89:CD006119. doi: 10.1002/14651858.CD006119.pub3.
Rustin GJ, van der Burg ME, Griffin CL, et al; Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet. 2010 Oct 2376(9747):1155-63. doi: 10.1016/S0140-6736(10)61268-8.
Management of Suspected Ovarian Masses in Premenopausal Women; Royal College of Obstetricians and Gynaecologists (December 2011)
Buys SS, Partridge E, Black A, et al; Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Randomized Controlled Trial. JAMA. 2011 Jun 8305(22):2295-303. doi: 10.1001/jama.2011.766.
Rosenthal AN, Fraser L, Manchanda R, et al; Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol. 2013 Jan 131(1):49-57. doi: 10.1200/JCO.2011.39.7638. Epub 2012 Dec 3.
Jacobs IJ, Menon U, Ryan A, et al; Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2015 Dec 16. pii: S0140-6736(15)01224-6. doi: 10.1016/S0140-6736(15)01224-6.