CA125 may be elevated in many physiological and pathological conditions, with gynaecological and non-gynaecological causes.  These conditions are summarised in the table below.

Primary Care

NICE recommends CA125 testing in primary care in women presenting with  1 of these following symptoms on a persistent or frequent basis, particularly if ≥ 12 x per month.

• Persistent abdominal distension (‘bloating’)
• Early satiety +/- loss of appetite
• Pelvic or abdominal pain
• Increased urinary urgency +/- frequency
• Unexplained weight loss
• Unexplained fatigue
• Unexplained change of bowel habit
• New onset of symptoms suggestive of IBS if 50 years

If CA125 is elevated >35 IU/ml, arrange an Ultrasound of the Pelvis – ideally Transvaginal Scan within 2 weeks.

Additionally if physical examination in primary care suggests ascites and or a pelvic or abdominal mass (which is not obviously uterine fibroids) they should be referred urgently for review in gynaecology and referral should not be delayed whilst waiting for CA125 result. 

Secondary Care

Abnormal Ultrasound Scan or imaging findings – premenopausal women

The Royal College of Obstetricians and Gynaecologists (RCOG) advises that a CA125 level is not routinely needed for the diagnosis of a simple cysts in premenopausal women. 

If germ cell origin tumours are suspected following imaging (e.g. women < 40yrs), αFP, βHCG and LDH are recommended in addition to CA125.

Please see GGC guidelines for further details.

Abnormal Ultrasound Scan or imaging findings – postmenopausal women

A CA125 level should be measured in all postmenopausal women with a cystic lesion of 1cm or more.  This should be used in conjunction with the USS findings to calculate the Risk of Malignancy Index Score (RMI).  Please see GGC guidelines for further details.

Normal pelvic ultrasound scan or imaging & Raised CA125

If a CA125 has been measured prior to imaging, a normal ultrasound can exclude ovarian cancer with a high degree of confidence. 

Postmenopausal ovaries will appear smaller and more homogenous compared to those found in pre-menopausal women. It is therefore common not to visualize the ovaries on ultrasound in a postmenopausal woman.  For completeness an abdominal examination and bimanual examination may be undertaken to assess for potential non pelvic masses.

In the presence of a normal pelvic ultrasound scan or imaging, there is no clear evidence to repeat a CA125 measurement.  However, extrapolating from ovarian cyst data, a rapidly rising CA125 is more likely to be associated with malignancy, therefore consider a repeat CA125 after 8 weeks to assess trend.  If significantly rising, further imaging by urgent CT scan of abdomen and pelvis should be arranged. 

If no gynaecological cause identified, patient should be referred back to GP to assess for other clinical causes of symptoms and investigate or refer as appropriate.