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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

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Comments

zoe derby May 27, 2015

Well i think it is very good and the research is great work put in by a number of
More women need to read and learn,including try to benefit from the research information being conducted
The website is easy to use and follow up with outcomes

zoe derby May 27, 2015

Well i think it is very good and the research is great work put in by a number of professionals .
More women need to read and learn,including try to benefit from the research information being conducted
The website is easy to use and follow up with outcomes

Nick Peel May 11, 2015

Dear Layla,
Thanks for your comment, and we’re sorry to hear about your mother.
If you have questions about your situation you can call one of the Cancer Research UK nurses free on 0808 800 4040 9am-5am Monday to Friday. Or you can email them via this online form.
Best wishes,
Nick, Cancer Research UK

Ann Everett May 10, 2015

I know I’m not referring to ovarian cancer which I know is very hard to detect but what about the admittedly small minority of us with clear cell cancer? I had always had smear tests but after very slight post menopausal bleeding & a “precautionary” hysterectomy I was diagnosed with a tumour only seen in 40 people worldwide! I feel that there must be a link to ovarian cancer! Your comments would be appreciated but to be honest I have had no interest because my tumour is so rare & therefore no connection or funding available.. Your comments would be appreciated. Thanks

Layla kolb May 9, 2015

My concerns are that I’m 42 and dealing with my 62 year old mother who was misdiagnosed with stage 3 and now had secondarys ,they won’t check me as we have no other family to contact to find out if I have the gene ..
I willing to have a hysterectomy to prevent any risks but they have refused to test me ,I’m so worried not sure waiting until 50 is good enough surely preventing this is better than cure and I’m the long term better for the NHS .

Irene Matley May 7, 2015

I can confirm that the blood test CAN find cancer. I was on the Ovarian Cancer UKCTOCS trial in Manchester and, on my very last blood test, my CA125 levels had risen. As they had a base line due to the number of tests I had had previously, they called me back for further blood tests. I had three in total, and then they sent me for a blood test and an internal scan. This revealed nothing , so they sent me for an CT scan, which revealed I had lung cancer! Had I not been on the trial, I would probably not be here today. These trials really work

Magda McHugh May 7, 2015

I realise you are managing expectations here but please try to be more enthusiastic about this news. It’s amazing progress. Something that doubles the figures for early detection of ovarian cancer offers hope to twice the number of women diagnosed. It’s a reason for cautious celebration. Let’s continue fundraising to support this project to make it life saving as well as life changing.

Elizabeth (Aust) May 7, 2015

I’ll be taking a CLOSE look at the evidence if they start promoting this test. CA125 blood testing led to false positive findings and women went on to have unnecessary testing and even excess surgery. (it did not save lives)
Sadly, vested interests make a fortune from cancer screening, especially women’s cancer screening. There is no doubt in my mind that women’s cancer screening is more about massive profits for vested interests. The pap test, a screening test for an always-rare cancer, (in the developed world) has led to widespread harm, huge numbers have been over-treated and many left worse off. There are no randomized controlled trials for pap testing, none.
The shocking thing is women have been ordered, and even coerced, into screening (including inappropriate and over-screening) – the law and proper ethical standards says informed consent is a MUST for all cancer screening, in cervical screening there is often no consent at all. I’d say informed consent is also, missing from breast screening. UK women are receiving more real information, but here Breast Screen are still using celebrity endorsement to convince women to screen.
Heads should roll over the treatment of women by these programs.

I’ve always declined pap testing, content with my near zero risk of cc, rather than accept the high risk of over-treatment, now I understand that HPV- women cannot benefit, about 95% of women aged 30 to 60 are HPV- not at risk of cervix cancer and are having unnecessary pap testing. (this is great for profits though, huge numbers end up being over-treated) We should not do pap or HPV testing on those under 30, it doesn’t help, but leads to high numbers of false positives and over-treatment.
I don’t have breast screening either, the risks exceed any benefit. The Nordic Cochrane Institute has an excellent summary of the evidence on their website, REAL information, not scary stories, a sales pitch, not patronizing lectures or any of the usual approaches.

I will never understand how these programs have managed to get away with ignoring both informed consent (and often consent itself in cervical screening) and have been permitted to mislead, scare and pressure women into screening….we are not mere bodies to be counted off like ignorant sheep. Our medical leaders and associations should be ashamed of their conduct, they have protected these programs, not women.

If this test does not satisfy MY risk v benefit assessment, I won’t hesitate to reject it. I would never accept a word coming from the medical profession and others with a vested interest in screening. Ovarian cancer is also, fairly rare, I’m not prepared to accept much risk at all to screen for a rare event. Of course, annual blood tests will cost a lot of money, someone will do well out of a new screening program, let’s make sure this time that benefit is not confined to vested interests, while huge numbers of women are harmed.

Katie H May 6, 2015

“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.” I think you mean 30 out of 100, right?