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A simple blood test may be much better at identifying ovarian cancer in primary care than was previously thought. New research found that the test, for women with abdominal symptoms such as pain or bloating, was most accurate in the over 50s. The test measures levels of a protein called cancer antigen 125 (CA125) in the blood. As well as identifying ovarian cancer, it also picked up other cancers including those of the pancreas and lung.

Women with symptoms that suggest ovarian cancer often take this blood test to measure levels of CA125.  It is available at GP practices in England, but no large studies have evaluated its effectiveness at detecting the disease in this setting. 

In a new study, researchers analysed data from 50,000 women who had taken the test at their GP surgery. Ovarian cancer is more common in the over 50s, so they analysed the risk at various ages and CA125 levels. They then developed a model to estimate the probability of ovarian cancer based on age and blood test result. The model will be evaluated further but it could allow GPs to give women with symptoms an individual assessment of their risk of ovarian cancer.

Women at risk of other cancers were also identified. The study found that, especially when ovarian cancer has been ruled out, a high level of CA125 in a woman over 50 could suggest another type of cancer. The researchers hope this information will guide GPs' decisions on the need for further investigation or urgent referral to specialists. 

What’s the issue?

Ovarian cancer is the sixth most common cancer among women in the UK, with 7000 women diagnosed every year. It mainly affects women who have been through the menopause (usually over the age of 50). Most ovarian cancers are not diagnosed until the disease is fairly advanced and harder to treat. Fewer than half of women with ovarian cancer survive for more than five years after receiving a diagnosis. 

Early detection of ovarian cancer gives the best chance of survival. However, diagnosing the disease early is challenging because the symptoms of ovarian cancer (such as persistent bloating and abdominal pain) are not specific and could be attributed to other health problems. There are no screening tests for women without symptoms.

In 2011, the National Institute for Health and Care Excellent (NICE) – which provides guidelines for healthcare professionals – recommended that GPs measure CA125 levels in women with symptoms that could be ovarian cancer. Women with an abnormal result (CA125 of 35 U/ml or above) are referred for further investigation. But the cut-off level for referral is the same for all women, regardless of their age.

The test is available at GP surgeries, but it has only been evaluated in specialist hospital settings and in screening studies involving women with no symptoms. Researchers wanted to see how well it can detect cancer in GP practices, where women with ovarian cancer symptoms usually first seek help. 

What’s new?

Researchers used anonymised patient data from more than 50,000 women who had a CA125 blood test at their GP surgery between 2011 and 2014. The women often had symptoms such as abdominal pain or bloating, or a change of bowel habit. 

The team used a national cancer registry to identify which women were later diagnosed with cancer. Overall, 456 (0.9%) of the women had ovarian cancer and 1,321 (2.6%) had other cancers.

The main findings

    • The blood test detected more than three in four (77%) of all ovarian cancers and more (85%) of invasive ovarian cancers which are most likely to be fatal
    • More than one in three (38%) of the ovarian cancers were picked up early (stage I or II) when treatment is most likely to be successful
    • The risk of ovarian cancer varied substantially according to age. Women with a CA125 above the NICE cut-off (35U/ml) were much more likely to have ovarian cancer if they were over-50 (15% chance) than if they were under-50 (3%)
    • Older women (70 years +) with CA125 below the NICE cut off (32 U/ml) had the same risk of ovarian cancer as 40 year olds with a much higher level (104 U/ml)
    • Almost one in three women over 50 with CA125 above the NICE cut-off were diagnosed with some form of cancer: 10% with ovarian cancer, and a further 12% with another type such as lung, pancreatic or gastrointestinal cancer.

Why is this important?

The results suggest that a CA125 blood test is a useful tool for GPs to detect ovarian cancer in women over 50. It might be a more reliable indicator of the disease than has been thought. The study found the proportion of women with elevated CA125 levels who had ovarian cancer was 12 times higher than the estimate used to inform the NICE guidelines, suggesting the advice should be updated. 

However, they say that CA125 tests in younger women should be interpreted with caution as their risk of ovarian cancer is much lower. NICE currently recommends that women with a CA125 level of 35 (U/ml) or above should have an ultrasound scan. The advice is the same for all levels of CA125 above this cut-off, and for women of all ages. 

The model developed by the researchers will be evaulated further. But this study suggests it gives a more accurate and personalised assessment of women’s risk, taking both CA125 level and age into account. It would trigger investigation for some older women who are currently considered to have ‘normal’ CA125 levels.   

The research also found that a CA125 blood test could be useful for detecting other types of cancer in the over 50s. The researchers say that GPs should be aware of this possibility for a woman with an abnormal CA125 test result, in whom ovarian cancer has been excluded. These women may need further investigation for other cancers.

The study is the first to estimate cancer risk in primary care based on CA125 levels and age. 

What’s next?

The CA125 blood test is already used in the UK and other countries for detecting ovarian cancer in primary care. However, the researchers want GPs to know that it could also be a useful indicator of the presence of other cancers, which could lead to an earlier diagnosis and therefore better outcomes for patients. 

The researchers plan to further evaluate their risk-calculator models in another group of women. If the models show good performance, they could be integrated within GPs’ clinical computer systems so doctors can make more informed decisions about a patient’s cancer risk. 

The models require only the woman’s age and CA125 level and risk could be reported to women in a straightforward way, for example: “One in 30 women of your age who have the same CA125 level in general practice will have ovarian cancer”. 

You may be interested to read

The full paper: Funston G, and others. The diagnostic performance of CA125 for the detection of ovarian and non-ovarian cancer in primary care: A population-based cohort study. PLoS Medicine 2020;17:10 

A post on Cancer News from Cancer Research UK about the study: An existing blood test for ovarian cancer has been re-evaluated. The results are in.  

A post on CanTest from the study researchers: Blood test predicts ovarian cancer better than previously thought.  

Funding: The NIHR School of Primary Care Research. This research arises from the CanTest Collaborative, which is funded by Cancer Research UK. 

Conflicts of Interest: None declared.

Disclaimer: NIHR Alerts are not a substitute for professional medical advice. They provide information about research which is funded or supported by the NIHR. Please note that views expressed in NIHR Alerts are those of the author(s) and reviewer(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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