Thursday, October 20, 2016

Is CA 125 a non-invasive, accurate rule in test for endometriosis: a systematic review and meta-analysis.

Clinical pearls:

  • CA 125 serves as a good rule in diagnostic marker for endometriosis at levels ≥ 30 units/ml in women presenting with symptoms and negative sonography. 
It is estimated that 10% of women have endometriosis during the reproductive years with a total of more than 10 million women in US suffering with it currently. It is the number one cause of infertility with high prevalence of 25-30% among infertile women.

Physicians often suspect endometriosis on the basis of history, symptoms, direct visualization, sonography or physical findings.[1]

It is challenging to make a confirm diagnosis unless a sample is obtained by laparoscopic surgery and histology is done. The test in invasive, expensive, and involves surgery that has its own complications. Hence it is often underdiagnosed or the diagnosis is delayed. According to Ballweg ML, an analysis of 7000 confirmed cases showed that the average time to diagnose is >9 years. [2] 

The delay results in symptom deterioration and diseases progression.

The investigators wanted to find out whether a simple, non-invasive blood test can rule out endometriosis. This will save time, money and also better unable the physician to formulate a management plan in such patients.

Research into mechanism of endometriosis have led to the discovery of potential serum markers used for diagnosing the disease.

CA-125 serum concentration has been associated with many gynecological diseases.  CA-125 antigen is expressed in many tissues derived from coelomic epithelia like ovary, fallopian tube, ovary, peritoneum and endometrium.[3] It is the most investigated and studied noninvasive marker for diagnosis of endometriosis. But, studies have come up with varied results that are not consistent and cannot be applied for ruling out endometriosis.

A systemic review and meta-analysis published in the British Journal of Obstetricsand Gynecology evaluates the diagnostic accuracy of CA 125 for endometriosis.[4]

This meta-analysis includes 22 studies with a total of 3626 subjects with surgically diagnosed endometriosis. The patients were classified into mild (stage I-II) and severe (stage III-IV) according to classification by American fertility society.

In the final analysis 14 studies with 2920 subjects (1584 with endometriosis, 1336 controls) were analyzed to assess the presence of endometriosis at CA 125 cut-off value of ≥ 30 units/ml.

The review found that CA125 showed increasing sensitivity as the disease stage 24.8% at stage I–II versus 63.1% at stage III–IV with an average sensitivity of 52.4%.

The authors concluded that at value of ≥ 30 units/ml Ca 125 serves as good rule in test in patients with symptoms but unfortunately CA 125 < 30 units/ml, does not rule out endometriosis with 49% of those with a negative test may still have endometriosis.

Other markers that are currently investigated are human epididymis protein 4 and miRNA which hold vast potential to be an accurate bio-marker in future.

In the absence of other noninvasive test at present, the investigators advocate that CA 125 ≥ 30 units/ml is highly specific for endometriosis in symptomatic women with a negative USG. These patients should be provided with early treatment plans with medical and surgical options.

In patients with CA 125 levels < 30 units/ml, further investigations are required.


[1] http://www.endtoendo.com/Endometriosis_Prevalence_End_to_Endometriosis.html
[2] https://www.ncbi.nlm.nih.gov/pubmed/15157638
[3] Jacobs I. Screening for ovarian cancer by CA-125 measurement. Lancet 1988;1:889
[4] http://onlinelibrary.wiley.com/doi/10.1111/1471-0528.14055/full

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