As we reported on our news feed this morning (and was widely covered elsewhere – with some predictably OTT headlines), UK researchers have developed a new, improved method of detecting ovarian cancer.

It looks at changes in the levels of a protein – called CA125 – in a woman’s blood over time, and calculates whether she needs further tests (such as ultrasound).

It’s certainly promising. In their study, published in the Journal of Clinical Oncology, the new method detected eight out of 10 women who have the disease: a big improvement on previous methods.

But, as is so often the case when the news says there’s ‘a simple blood test’ for cancer, it’s never quite that simple.

That’s because we’re still missing concrete proof that using the test actually saves lives.

Thankfully, the team behind today’s findings has also spent the last 14 years running a trial to answer exactly that question. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is jointly supported by Cancer Research UK, the Medical Research Council, the Department of Health, and the Eve Appeal. And its results are expected later this year.

So how does this fit into the bigger picture? And what does the future hold for possible routine NHS screening for ovarian cancer?

Ovarian cancer screening – the story so far

Ovarian cancer affects about 7,100 women each year, and is notoriously difficult to diagnose early. Its symptoms can be vague, and difficult to tell apart from other more common, less serious problems.

But spotting it early makes a big difference. When diagnosed in its earliest stages, 90 out of 100 women survive at least five years. That plummets to fewer than 3 out of 100 women if diagnosed after it’s spread.

Could routine screening make a difference? Two large trials have set out to test this idea – the UKCTOCS trial, and a large US trial called PLCO. Both trials studied a combination of two medical tests: the CA125 blood test, and ultrasound scans.

Disappointingly, in 2011 the PLCO trial found that:

Among women in the general US population, simultaneous screening with CA-125 and transvaginal ultrasound compared with usual care did not reduce ovarian cancer mortality.

In other words, although the tests spotted women with the disease earlier, it didn’t spot them early enough to reduce the number of deaths. And, in addition, the women who had false positive results had additional complications.

According to the PLCO trial, the harms of ovarian screening seemed to outweigh the benefits.

So focus switched to the UK trial. Would it confirm these results?

UKCTOCS: the biggest… and best?

In 2001, a group of researchers led by a team at University College London, began inviting women between 50 and 74 to take part in an ovarian cancer screening trial.

By 2005, they’d recruited more than 200,000 women to the largest ovarian screening trial ever conducted.

They were randomly assigned to one of three groups:

  • A quarter of them – about 50,000 – were offered a combination of regular CA125 blood tests, followed up with ultrasound if their CA125 levels looked suspicious.
  • Another 50,000 were offered regular ultrasound tests.
  • As a comparison (‘control’) group, the remainder – about 100,000 were not offered any screening.

These women have been followed up regularly ever since. And the researchers are now reaching the point where they have enough evidence of what’s been happening to make valid, statistically accurate conclusions about whether screening’s been effective.

We’re expecting their final results later this year.

So why is this different from the US trial?

Changes over time

Ultrasound

Ultrasound is also used to detect ovarian cancer

Both UKCTOCS and the US trial looked at CA125 and ultrasound. But there’s an important difference: in the US, women were flagged as being likely to have ovarian cancer if the levels of CA125 in their blood were above a certain specified level.

The UK trial, on the other hand, did something more sophisticated. Realising that no two women are the same (and so might have different ‘background’ CA125 levels), the team looked at how CA125 levels changed over time. They could then see if a woman was more likely to have cancer if their CA125 levels changed compared to a previous measurement, rather than if they tipped a pre-specified cut-off.

This, they surmised, would account for differences among different women, and potentially be far more sensitive.

Which brings us to today’s headlines.

The research team has published what is effectively a comparison between the ‘cut-off’ method used by the US team, and the ‘changes over time’ method used in the UK trial (known technically as the ‘Risk of Ovarian Cancer Algorithm’, or ROCA).

The cut-off method generally identifies four out of 10 women who subsequently turn out to have ovarian cancer.

According to today’s results, the ROCA algorithm can identify more than eight out of 10 women – a big improvement.

But today’s results say nothing about whether detecting these women’s cancers made a difference to whether they survived.

Nevertheless, it suggests that the UKCTOCS trial might show a different balance of benefits and harms to its US counterpart.

So what happens next?

We still need to wait for the UKCTOCS final results later this year before we’ll know if this method can actually save lives, and whether its benefits outweigh the possible harms.

And even if it does, there are still several possible hurdles ahead.

Firstly, will the UK results be strong enough to outweigh the fact that the US trial was negative? When researchers tried to look back at whether using the ROCA method on data from the US trial would have made a difference, they found it wouldn’t have shifted the balance towards a positive trial result.

Secondly, the data will need to be scrutinised by Government bodies like Public Health England’s National Screening Committee, which will ultimately decide whether women in the UK should be routinely invited for ovarian screening. We’re expecting them to review all the data on ovarian screening in late 2015, after the UKCTOCS results are in.

And finally, if the Committee does give ovarian screening the green light, the appropriate infrastructure will need to be put in place, and piloted, to reliably run any possible programme. And this would all take time.

And what if UKCTOCS is negative? Will that be the end of the road for ovarian screening? Maybe not. It’s likely that researchers will then pore over the data, looking at whether any sub-groups of women benefitted more than others. Does, for example, their genetic background or family history make a difference? Or are there particular benefits for a narrower age range?

Even if not, are there better tests than CA125 or ultrasound? Or can other markers of the disease be used to spot it early?

The fundamental challenge of detecting ovarian cancers earlier is something that we will continue to try to tackle. It’s a disease that claims more than 4000 women’s lives every year – we owe it to their families not to give up. And we’ll be crossing our fingers for the UKCTOCS team, as they analyse the data from their trial. Watch this space.

Henry

Read more: ovarian cancer symptoms

Reference

  • Menon, U. et al. (2015). Risk Algorithm Using Serial Biomarker Measurements Doubles the Number of Screen-Detected Cancers Compared With a Single-Threshold Rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening Journal of Clinical Oncology, 33 (18), 2062-2071 DOI: 10.1200/JCO.2014.59.4945

Images