NICE proposes age-based CA125 test thresholds to improve ovarian cancer referrals

The National Institute for Health and Care Excellence (NICE) has published draft guidance proposing new age-specific thresholds for interpreting the CA125 blood test — a first step towards more personalised and accurate detection of ovarian cancer in primary care. The move is aimed at helping GPs identify women at higher risk of ovarian cancer earlier, while reducing unnecessary investigations in those at lower risk.

Ovarian cancer affects around 1 in 50 women in their lifetime, with roughly 7,000 new cases diagnosed annually in the UK. It is often detected at an advanced stage because its symptoms — such as bloating, abdominal discomfort and feeling full quickly — are non-specific and easily mistaken for less serious conditions.

Replacing the one-size-fits-all threshold

Under current guidance, a CA125 level of 35 IU/ml or higher triggers further investigation or referral for any woman with symptoms suggestive of ovarian cancer. However, NICE’s draft update recommends different CA125 cut-offs based on age, recognising that both ovarian cancer risk and the typical CA125 level change as women get older.

According to the draft recommendations:

• Women and people with female reproductive organs aged 40–49 would continue to have 35 IU/ml as the referral threshold.

• Those aged 50–59 would have a lower threshold of approximately 31 IU/ml.

• Women in their 60s and 70s would have thresholds of around 24–25 IU/ml.

• People aged 80 and over would again have a threshold near 31 IU/ml.These stratified thresholds aim to reflect evidence that older women can have ovarian cancer even with lower CA125 levels, while younger women with higher values are less likely to have malignancy.
  

The new approach also clarifies that for people under 40, CA125 alone is not sufficiently accurate; ultrasound scanning should be considered directly for those with persistent symptoms.

Supporting evidence and expert commentary

The updated thresholds are informed by research showing that CA125’s predictive value varies with age, and that age-based models may better discriminate between cancer and benign conditions in primary care settings. Large population studies have validated models incorporating age alongside CA125 to improve referral decisions compared with the single-threshold approach.

Professor Azeem Majeed, a GP and head of the Department of Primary Care and Public Health at Imperial College London, described the proposed updates as giving GPs “more precise, evidence-based tools to assess the risk of ovarian cancer”, noting that replacing one threshold with age-based criteria could help identify older women at higher risk more reliably while reducing unnecessary investigations in younger women.

Additional measures and consultation

Alongside age-based CA125 cut-offs, the draft guidance proposes that people aged 60 and over with unexplained weight loss (defined as more than 5 per cent of body weight over six months) should be considered for urgent investigation or referral via the suspected cancer pathway.

The guidance also highlights a need for research into when unexpected bleeding while on hormone replacement therapy (HRT) warrants investigation for endometrial cancer, reflecting rising HRT use in England.

The public consultation on the draft recommendations is open until 2 February 2026, during which clinicians, patients and other stakeholders can submit comments via the NICE website.

What it could mean for patients

If adopted, age-based CA125 thresholds could help reduce delays in ovarian cancer diagnosis, particularly in older women who may currently have values below the fixed 35 IU/ml cut-off but nonetheless harbour cancer. The personalised thresholds also aim to reduce unnecessary ultrasounds and referrals for younger patients with benign conditions — potentially freeing up NHS diagnostic capacity.

Early diagnosis of ovarian cancer can significantly improve outcomes, underlining the importance of refining referral criteria in primary care. NICE’s proposals represent a data-driven effort to target investigative resources where they are most needed while supporting GPs with clearer, age-alternated guidance.