Improving ovarian cancer detection: new age-specific CA125 thresholds proposed

Every year there are around 7,600 new cases of ovarian cancer diagnosed in the UK (CRUK). It is notoriously challenging to diagnose early, often presenting insidiously with non-specific symptoms. With the latest data from the National Ovarian Cancer Audit showing that over 30% of patients in England had stage 4 disease at diagnosis, the impetus to explore new ways of improving diagnosis is clear. CA125 testing offers the benefit of being readily accessible from primary care, however significant false positives and negatives have led to controversy over its use. 

Enter welcome draft updates to NG12 from NICE, promising ‘more personalised, targeted testing, so women at greatest risk of ovarian cancer are identified and referred sooner’ Eric Power, deputy director, Centre for Guidelines (NICE 2026).   

First, a quick reminder of the current guidelines:

Currently NG12 advises first measuring CA125 if patients present with symptoms suggestive of ovarian cancer (i.e. persistent abdominal distension/bloating, early satiety, loss of appetite, pelvic/ abdominal pain, increased urinary urgency and/or frequency, unexplained weight loss, fatigue or change in bowel habit).  They stress that testing is particularly relevant for those aged 50 and over but include no other age stratification. Ultrasound scan of the abdomen and pelvis is advised for all with a CA125  ³35IU/ml.

What are the proposed changes?

The draft NICE guidance advocates an age-stratified approach to CA125 testing. Signalling a key change in practice, it advises ‘do not use serum CA125 measurement in isolation for decision making for patients aged 39 and under’. Whilst the risk of ovarian cancer is lower in younger patients this does not equate to NICE advising against investigation! Rather, it reflects the fact that the low prevalence in this age group affects the performance of the test and increases the risk of false reassurance from CA125 testing, which may lead to late diagnosis. Instead, they advise to consider an ultrasound scan for those 39 and under, if they have persistent symptoms of ovarian cancer. This is more in line with the Scottish guidelines, which advocate pelvic ultrasound for all patients over the age of 18yr, with symptoms suggestive of ovarian cancer, alongside CA125. 

NICE continues to advise measuring CA125 first line for those 40 and over with symptoms suggestive of ovarian cancer. However, rather than a universal cut off of 35 IU/ml, the threshold for ultrasound scan would depend on age bracket, generally decreasing with age, with the much lower threshold of 24 IU/ml for scan referral for those in the 60-69 yr age group. The aim is to reduce the threshold for imaging for cohorts most at risk of ovarian cancer, without increasing unnecessary imaging and worry for other groups.

This age tailored approach is in keeping with findings from a UK primary care based cohort study previously discussed on Hot Topics; which included data from over 50 000 women via the UK CPRD and demonstrated variable performance of the CA125 test by age. Cancer was more common in women with raised CA125 levels if patients were over 50yrs, and the 3% probability threshold for urgent cancer investigation was met at progressively lower levels of CA125 for older women up to 70yrs.

Importantly, the study also found that just over 20% of women aged ≥50 years with a raised CA125 ≥35 U/ml who did not have ovarian cancer went on to be diagnosed with a non-ovarian cancer, highlighting the need to consider broader investigation in the advent of a normal scan in this cohort. 

What now?

It is important to stress that as these are draft guidelines details may change, with the finalised update due in March 2026. However, this is a welcome indication of direction of travel towards more targeted, age specific CA125 thresholds for imaging. 

In the interim, we should be aware of the limitations of CA125 particularly for those under 40, considering pelvic ultrasound for those with persistent symptoms. The proposed stratification of investigation serves as a reminder that the risk of ovarian cancer increases sharply with age over 50, peaking in the 60’s and 70’s. This is the patient cohort of where we must have the highest index of suspicion. 

What about those with negative tests? As above, we should be alert to the risk of non-ovarian cancers  associated with raised CA125. Both draft and current NICE guidelines emphasise the need to safety net, advising patients to seek review if symptoms persist or worsen despite reassuring CA125 or scan results. If your clinical ‘Spidey sense’ tells you something is wrong, then listen!