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New test could improve diagnosis of ovarian cancer

Tuesday 5 May 2015

"New ovarian cancer test twice as effective as existing methods," The Guardian reports, after new research proved relatively successful in diagnosing ovarian cancer.

This study hasn't identified a new blood test for cancer as such – instead, it is a refinement of existing diagnostic methods. The blood test looks at levels of the protein CA125, long recognised as a marker for ovarian cancer.

But this marker is not very reliable – some women with ovarian cancer don't have raised levels, and levels can also be raised in non-cancerous conditions.

This study has developed a new algorithm called the risk of ovarian cancer algorithm (ROCA), which categorises cancer risk according to CA125 levels measured every year.

Around 50,000 women aged 50 or over were screened using ROCA:

  • women at normal risk carried on with annual screening
  • women at intermediate risk had CA125 repeated at 12 weeks
  • women at elevated risk had CA125 repeated at six weeks and a transvaginal ultrasound scan

High-risk women would then be referred for further assessment and surgery as needed. The algorithm accurately detected 86% of women with ovarian cancer, and ruled out almost 100% of women who were cancer-free.

The study suggests the new algorithm could be a valuable way of assessing risk of ovarian cancer, a cancer with notoriously non-specific symptoms. A reliable method of early diagnosis could save some women's lives.

But this is the key thing the research team still has yet to examine – whether screening using this method actually does save lives. Results for this are expected in the autumn.

Screening isn't a "magic bullet", and there has to be careful assessment of the risks of misdiagnosis and any cost implications. 

Where did the story come from?

The study was carried out by researchers from University College London, among various other hospitals and academic institutions in the UK.

It was funded by the Medical Research Council, Cancer Research UK, the Department of Health and the Eve Appeal.

Two study authors are co-inventors of the risk of ovarian cancer algorithm (ROCA), which is patented and licensed to Abcodia Ltd. Two other study authors also declare financial interests through Abcodia Ltd.

One of the authors declared a consultancy arrangement with Becton Dickinson in the field of tumour markers. The remaining authors declare no conflicts of interest.

The study has not yet been published online.

The media generally reported the findings accurately, though some reports give the impression a new test has been developed. This isn't technically a new test – it's a new way of interpreting the results.

The media also failed to mention that it isn't clear yet whether this could be introduced as a screening test, as there are many issues to consider.

Professor Usha Menon of University College London told the BBC News website that, "It's good, but the truth lies in whether we've picked up the cancer early enough to save lives", adding that they don't know this yet. 

What kind of research was this?

This was a randomised controlled trial (RCT) looking at whether annual blood tests for a biomarker of ovarian cancer might be a useful cancer screening tool. The biomarker being examined is called CA125. It has long been recognised that levels of this marker can be raised in ovarian cancer.

However, it's not a specific marker for ovarian cancer as it can also be raised by other conditions, such as infection or inflammation. Also, some women with ovarian cancer don't have raised CA125, so it isn't very good at picking up ovarian cancer on its own.

The research team devised a new way of looking at changes in levels of CA125 over time using an algorithm. 

This publication reports on women in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) who were allocated to the multimodal screening arm of the trial. These women had their CA125 levels measured every year and interpreted using the risk of ovarian cancer algorithm (ROCA).

Other arms of the trial not reported here included a group who received screening by ultrasound scan (around 50,000 women) and a control group who received no screening (around 100,000 women).  

What did the research involve?

A total of 46,237 women aged 50 years or older were involved in the multimodal screening arm of the trial. Each year, their CA125 levels were measured. Based on these levels, their risk of ovarian cancer (ROC) was interpreted on the algorithm as:

  • normal – return to annual screening
  • intermediate – repeat CA125 in 12 weeks (repeat level I screen)
  • elevated – repeat CA125 and transvaginal ultrasound in six weeks (level II screen) with earlier screens arranged where clinically suspicious

A transvaginal ultrasound scan (TVS) uses high-frequency sound waves to create an image of the ovaries. This image can show the size and texture of the ovaries, plus any cysts or other swellings present.

The way the ROC risk categories were set meant about 15% of all screened women would be in the intermediate ROC category and 2% would be in the elevated ROC category.

For the minority of women in the elevated category, follow-up actions after the level II screen six weeks later would be as follows:

  • TVS normal and normal/intermediate ROC – return to annual screening
  • TVS normal and elevated ROC – repeat level II screen six weeks
  • TVS unsatisfactory, regardless of ROC – repeat level II screen six weeks
  • TVS abnormal – clinical referral

Women with a high ROC risk were recommended to be referred for further investigation and surgery as required.

Participants were followed up using national cancer and death registries. 

What were the basic results?

Overall, there were 296,911 annual screens carried out over an average of three years of follow-up. In this study arm, 640 women underwent surgery, 133 of whom were found to have ovarian cancer.

The researchers calculated that multimodal screening had a 85.8% sensitivity for ovarian cancer. This is the proportion of women with ovarian cancer who were correctly identified as being at risk by the ROCA algorithm.

The specificity was even better at 99.8%, the proportion of women without ovarian cancer who would be correctly identified as not being at risk by the algorithm. For each single case of ovarian cancer identified, 4.8 operations were performed.

However, the researchers also found that basing risk on a fixed CA125 cut-off level was much less accurate, and only would have identified about half of the women with ovarian cancer. 

How did the researchers interpret the results?

The researchers concluded that, "Screening using ROCA doubled the number of screen-detected ovarian cancers compared to a fixed [CA125] cut-off."

They also said that, "In the context of cancer screening, reliance on predefined single threshold rules may result in biomarkers of value being discarded." This implies that CA125 is a valuable biomarker when used in the right way. 


This is a valuable study that has reported the results for around 50,000 women aged 50 or over who were allocated to one arm of a larger trial. They had their ovarian cancer risk assessed annually using the risk of ovarian cancer algorithm (ROCA).

When CA125 levels were used to categorise cancer risk alongside this algorithm, the algorithm was able to accurately identify 86% of women with ovarian cancer. Encouragingly, it ruled out almost 100% of women who were cancer-free. This means these women would not undergo unnecessary further investigation and surgery.

The study suggests the new algorithm could be a valuable way of assessing ovarian cancer risk. This cancer has notoriously non-specific symptoms often only first detected when it is at an advanced stage.

But before any new screening test is introduced there has to be careful assessment of its risks and benefits. These include comparing it with other methods of detecting ovarian cancer based on an assessment of symptoms, clinical examination and investigation findings.

This study did not compare outcomes with the large number of women in the other two screening arms of the trial – those in the control group and those being screened by transvaginal ultrasound. Other issues also need to be considered, including resource implications.

This research doesn't yet say whether the screening saved any lives by detecting the cancer earlier so it could be treated more effectively.

On this point, Professor Usha Menon from University College London told the BBC News website: "There is no screening at the moment, so we are awaiting the results [on whether lives have been saved] before the NHS can decide. Many people would have to be screened, so it really needs to translate to lives saved."

BBC News reports the results of screening this are expected in the autumn. We will provide an update once these become available.

Analysis by Bazian
Edited by NHS Website