Early results from ovarian cancer screening trial look promising

Ovarian cancer treatment is more likely to be successful if the disease is detected early

As we’ve said before, ovarian cancer is difficult to spot.

Although it’s sometimes dubbed ‘the silent killer’, it does have a distinct set of symptoms, but they’re quite similar to those of many other diseases. As a result, many women aren’t diagnosed with the disease until it’s reached a late stage, when treatment is less likely to be successful.

But if ovarian cancer is detected early, then the chances of successful treatment are much higher.

So, to work out how to spot the disease early, Cancer Research UK, in collaboration with the Medical Research Council and the National Institute for Health Research, is funding a huge trial designed to see whether a national screening programme for ovarian cancer could be used to detect cancers earlier, and help to reduce the number of women dying from the disease.

And this week, the researchers running this trial published some of their early results in a paper in the journal Lancet Oncology. Let’s take a look at what they’ve found.

What’s the trial all about?

The trial, called the UK Collaborative Trial of Ovarian Cancer Screening (or UKCTOCS for short), has recruited more than 200,000 women aged between 50 and 74. The researchers are comparing two different methods of screening to see whether either of them could spot ovarian cancer early, and whether this could save lives.

Back in 2005, the researchers randomly divided the 200,000 women into three groups. The first group, of 50,000 women, are being screened every year with a blood test that measures the levels of a protein called CA125. This protein is often found at high levels in women who have ovarian cancer.

If the blood test shows that the woman has a high risk of ovarian cancer, an ultrasound examination is done. And if this test shows abnormalities, the woman will be referred to the hospital.

The second group of women, another 50,000, are being screened every year by having an ultrasound scan. This scan looks for visible abnormalities in the ovaries. If the test shows something unusual, the woman will have another, more detailed scan and then might be referred to the hospital.

The remaining 100,000 women formed the third group. This group is a ‘control‘  group, so they aren’t having screening. We’ll be able to see whether screening is effective by comparing these women to the screened women in the other groups in the trial.

The trial is set to continue until 2014, when the women in the three groups will all be compared to see how many of them have developed ovarian cancer, and how many have died of the disease. This will tell us whether screening can help to prevent deaths, and if so, whether one type of screening is better than the other.

Sensitivity and specificity

When designing a test for any disease, two things are really important. The first, obvious, one is how good the test is at picking up people that have the disease. This is called ‘sensitivity’. The second important factor is how good the test is at not picking up people that don’t have the disease, which is called ‘specificity’.

It’s important to get a good balance between sensitivity and specificity. A quick thought experiment will reveal why. Imagine a test where every single person that has the disease tests positive. This sounds great, but what if the reason this happens is because everybody who takes the test at all, regardless of whether or not they have the disease, tests positive? Clearly this would be a useless test in practice. Its highly sensitive but not in the least bit specific.

When a test comes out positive for someone who doesn’t actually have the disease, it’s called a ‘false positive’. Similarly if a person with the disease tests negative, it’s called a ‘false negative’.

(There’s an excellent discussion of sensitivity, specificity, and false positive rates – in the context of ‘screening for’ terrorists – on the Bad Science blog)

What have the researchers found?

The UKCTOCS team have calculated the initial sensitivity and specificity of the two screening methods being used in the trial.

The sensitivity was not significantly different between the two strategies, but the ‘blood test plus ultrasound’ screening had a better specificity than the ‘ultrasound only’ screening – i.e. ‘blood test plus ultrasound’ is much less likely to produce false positives than ultrasound alone. So a lot more women tested with only ultrasound would have to go through medical procedures they didn’t actually need.

The researchers suggested this is because ultrasound scanning is more likely to pick up harmless cysts in the ovaries, which are much more common among older women.

Some of the people with these cysts will have to undergo surgery to rule out ovarian cancer. The blood test seemed to be better at separating out women with non-cancerous cysts from women with ovarian cancer.

Early detection

Out of all 87 cancers that have been detected in the trial so far, nearly half were early-stage (stage I or II), which is a very encouraging result. When ovarian cancer is detected at an early stage, it is much easier to treat and survival rates are much higher.

So what does this all mean?

The results of the trial so far look promising and at this, admittedly early, stage, it looks like both types of screening test could be used to detect ovarian cancer earlier. But just detecting the disease earlier isn’t enough.

We’ll have to wait until 2015, when the trial has finished, before we know whether screening can actually help reduce the death toll of ovarian cancer – which currently claims over 4,000 lives each year.

Lead investigator Professor Ian Jacobs stressed:

There is a long way to go before we have firm evidence as to whether or not screening is able to detect cancer early enough to save lives. It will also be essential to balance any benefits offered by screening with the downside, as it is recognised that screening can cause anxiety and lead to some unnecessary operations.

I believe the UKCTOCS trial is an example of UK healthcare at its best. It is a combination of a huge research effort, involving charity, research council and Government funders, hospital staff, university researchers and GPs around the UK and crucially more than 200,000 women.

The first results are an important step forward and the trial itself is a powerful demonstration of how our best scientists, clinical researchers and healthcare workers in the UK collaborate in research and involve volunteers nationwide to improve health.

In the meantime, if you are worried about your risk of ovarian cancer, your GP will be able to help you. You can find out more information about the signs of ovarian cancer on CancerHelp UK, our patient information website.

There’s also a more detailed analysis of the UKCTOCS trial at NHS Choices

Jess Harris

Jess is a Health Information Officer at Cancer Research UK

Reference:

Menon, U., Gentry-Maharaj, A., Hallett, R., Ryan, A., Burnell, M., Sharma, A., Lewis, S., Davies, S., Philpott, S., & Lopes, A. (2009). Sensitivity and specificity of multimodal and ultrasound screening for ovarian cancer, and stage distribution of detected cancers: results of the prevalence screen of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) The Lancet Oncology DOI: 10.1016/S1470-2045(09)70026-9