Ovarian cancer screening disappoints, but lessons remain
A trial found that ovarian cancer screening doesn’t save lives, but the research still taught experts much about the disease
Ovarian cancer is often described as a “silent killer”. The symptoms, such as bloating, are vague and easily confused with those of non-life-threatening conditions like irritable bowel syndrome.
About 4,000 women in the UK die from ovarian cancer every year, according to Cancer Research UK. There is currently no national screening programme for detecting the disease, which mainly affects post-menopausal individuals.
Researchers hoped they could change that, saving thousands of lives. In 2001, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) began following more than 200,000 women aged between 50 and 74 from the general population. Participants were screened annually with either an ultrasound of their ovaries or a blood test, alongside a control group that did not undergo any screening.
The results were heavily anticipated. However, in May the large-scale trial found that screening failed to reduce deaths from ovarian cancer.
“With this disease, there is so much need,” says lead investigator Professor Usha Menon from the MRC Clinical Trials Unit at UCL, who has been working to improve ovarian cancer detection since the mid-1990s. “We thought this might be the solution that would change things. But we were disappointed.”
That means there won’t be a recommendation for routine screening. Still, experts say there are plenty of lessons to take from the study.
To screen or not to screen
Around 90% of women diagnosed with ovarian cancer at the earliest stage survive for five years or longer. But if the disease is detected at the latest stage, this figure plummets to just 13%. Almost six in 10 cases are diagnosed at a late stage.
Screening is designed to spot cancers as early as possible, when treatment is most likely to be successful. But a screening programme will only be approved for use in the NHS if it’s known to save lives. The test also needs to reliably detect cancer or abnormal changes that could lead to the illness, as well as being cost-effective and acceptable so people will actually take it.
There is good evidence that all of this is true for the UK’s existing early detection programmes for bowel, cervical and breast cancers. For ovarian cancer, however, the goal has yet to be achieved.
“For all the lives a future screening programme might save, there are going to be quite a few women who have surgery for what turns out not to have been cancer,” explains consultant gynaecologist Dr Adam Rosenthal from UCLH. “You can’t introduce general population screening with all the downsides until you’re really certain it is saving a substantial number of lives.”
Although UKCTOCS didn’t show a survival benefit, there were some hopeful findings. While annual ultrasounds couldn’t detect cancer earlier or save lives, researchers were able to find some ovarian cancers earlier than normal in women who underwent regular blood tests.
The test, which tracked levels of a chemical called CA125 that is released from ovarian tumours, picked up 39% more cancers at an early stage compared to the no screening group. As CA125 levels can vary between women, the researchers developed an algorithm that measured how someone’s levels changed over time. If their levels of CA125 rose during the trial, they were referred for an ultrasound scan.
Even a slightly earlier diagnosis can make a big difference to ovarian cancer patients in terms of treatment options and quality of life, says Tracie Miles, gynaecological cancer information nurse at The Eve Appeal. Detecting the disease at an early stage could mean less intense treatment with fewer hospital trips – and more time with loved ones.
Next steps for ovarian cancer research
So why didn’t early diagnosis save lives? It’s still a mystery to the researchers. Menon says it could be that screening did not pick up enough of these early cancers, or that they need to be detected even earlier to affect survival rates.
However, it’s possible that the blood test used in the UKCTOCS trial might help women who are at high risk of developing the disease. Some women have a gene that makes them significantly more prone to ovarian cancer. Rosenthal found that by screening these women every few months, it might be possible to diagnose the disease before it reaches an advanced stage.
Regular surveillance could give them a damage-limitation option until they’re ready to have a preventative operation to remove their tubes and ovaries. However, Rosenthal stresses the blood test is not an alternative to surgery, which is the only way of preventing ovarian cancer.
While the UKCTOCS results are disappointing, some experts laud the study as an extraordinary piece of research that will help scientists design future clinical trials. “Trials don’t always find the results that we hope for,” says Sophia Lowes, health information manager at Cancer Research UK. “But the results of UKCTOCS also clearly demonstrate how crucial it is to do long-term studies like this, because it’s the only way to know whether screening can save lives.”
And the research could live on. Women who took part in the study gave their permission for other researchers to use their data and blood samples, creating a rich database that might help scientists determine whether new tests for early diagnosis perform better than those used in the study.
Researchers could also look for different chemicals in the blood that could suggest ovarian cancer. And the information might even help further our understanding of how ovarian cancer develops in the first place.
What’s more, as the women in UKCTOCS were followed for so long, some were diagnosed with other cancers. Their data and samples will also help researchers who are working on early detection of other forms of the disease, such as lung, breast and bowel cancer.
It’s certainly not the end of the road for early detection in cancer care, says Lowes. The NHS is currently trialling another blood test, or “liquid biopsy”, developed by biotech company Grail to see if it can detect difficult-to-diagnose cancers (such as ovarian and pancreatic) in patients without symptoms. The health service hopes the test could increase the proportion of cancers that are caught early, one of the major goals of the NHS’s long-term strategy.
But until such methods show promise, most women with ovarian cancer will continue to be diagnosed after they go to their GP with symptoms. “It is really important that the results of UKCTOCS do not discourage the testing of women with relevant symptoms,” says Dr Garth Funston from the University of Cambridge, who studies the role that primary care plays in the early detection of cancers.
“It is key that as well as working towards developing an effective screening programme, we work to develop new approaches to ensure that women with symptoms are diagnosed and can receive treatment in a timely way.”
It’s still important to raise awareness of possible symptoms, which will play a crucial role in reducing deaths from ovarian cancer. Miles urges women – especially those aged over 50 – who are experiencing persistent bloating, unexplained bowel changes or abdominal pain or swelling to get it checked out. She also advises anyone with a family history of ovarian cancer to speak to a doctor, who might then arrange a genetic test.
“I don’t think ovarian cancer is the silent killer,” she says. “I think it whispers. We’ve just got to work out how to listen to it.”