NG12: the biggest ovarian cancer referral change in 15 years, and what it means for primary care

The April 2026 update changes the universal CA125 threshold of 35 IU/ml that has guided primary care for over ten years. Now, there are age-adjusted thresholds for women aged 40 and over. It also removes CA125 testing from the diagnostic process for women under 40.¹ For GPs, prescribing nurses and clinical pharmacists managing direct access investigations, this alters their daily test-ordering decision.

What’s actually changed

The previous NG12 recommendation told clinicians to measure CA125 in woman over 18 with persistent or frequent symptoms that might suggest ovarian cancer, with a positive result defined as 35 IU/ml or above. It applied that single threshold regardless of age. The committee reviewed recent evidence and found that CA125 performs poorly as an isolated test in younger women, where physiological elevations are common and specificity is low. In this group, normal variations are common, making it less specific. In older women, the test performs well but the threshold for action could be more nuanced. The updated guidance, set out in recommendations 1.5.6 to 1.5.11, takes two distinct positions. For women, trans men and non-binary people aged 40 and over, age-adjusted CA125 thresholds now apply. The specific values are in Table 1 of NG12. For people aged 39 and under, CA125 should not be used in isolation. Instead, consider urgent ultrasound of the abdomen and pelvis. NICE has also merged the ovarian cancer detection content from CG122 into NG12. Primary care should now refer only to NG12 for decisions on ovarian cancer recognition and referral. CG122 retains content on initial management after diagnosis only.

Why this matters for daily practice

The practical impact lands in three places. The first is the test-ordering decision itself. EMIS, SystmOne and Vision templates that automatically include CA125 with a 35 IU/ml flag will need updates to reflect the age-adjusted thresholds, and to remove CA125 as a default test for women under 40. Practices using pre-set symptom-driven investigation panels should audit these in the coming weeks. The second is direct access ultrasound capacity. The under-40 cohort now triages straight to ultrasound rather than to a blood test. Local imaging services will see changes in referral patterns. So, ICBs may need to review their pathway capacity. Expect some early delays while services adjust, and consider how this affects the suspected cancer two-week wait pathway in your area. The third is patient communication. Women who have previously been told their CA125 was normal at 35 IU/ml will now get results based on an age-adjusted figure. For older women, a CA125 result that once seemed safe may now warrant further investigation. The shift from one threshold to age-based interpretation means clinicians must explain the test's role differently. Also, patient information leaflets will take time to catch up with this change.

The wider package

The April 2026 update includes two further changes worth noting. New recommendations for endometrial cancer about unscheduled bleeding during systemic HRT are now included in sections 1.5.12, 1.5.14, and 1.5.15. These updates align NG12 with the menopause guideline NG23. Clinicians should consider referring women on HRT for endometrial cancer if they have unscheduled bleeding. NG12 outlines the specific clinical criteria for this referral. A new non-site-specific recommendation on weight loss as a presenting symptom has also been included at recommendation 1.13.2.

What to do this week

The audit list is short but worth completing before the next quiet morning. Update practice clinical templates to reflect the age-adjusted CA125 thresholds and to remove the test as a default for women under 40. Update the reception and triage staff on the change, particularly where direct access ultrasound is now the first investigation. Review local two-week wait and direct access ultrasound pathways with the ICB to anticipate referral pattern shifts. And consider how the practice will communicate the change to women who have previously had CA125 testing under the old threshold.

For background on primary care diagnostic challenges, check our recent coverage on interim diagnoses and missed cancer diagnoses from the BJGP qualitative study published in April.

References

1. National Institute for Health and Care Excellence. Suspected cancer: recognition and referral [NG12]. Updated 15 April 2026. Available at: https://www.nice.org.uk/guidance/ng12

Medicine Central is a clinical evidence review for UK primary care clinicians. Content reflects evidence current at time of publication and should be read alongside local formulary and clinical guidance. Guest contributors retain responsibility for the accuracy and originality of their work. Views expressed are the author's own and do not necessarily reflect those of Medicine Central. For healthcare professionals only.