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Ovarian cancer screening trial did not save lives

by Katie Roberts | Analysis

12 May 2021

15 comments 15 comments

Ovarian cancer micrograph

“The effort from the start was to save lives of women with ovarian cancer. To build evidence for a screening programme that the NHS could introduce. To have an impact on the lives of thousands of women who are affected by ovarian cancer each year.”

Professor Usha Menon, a gynaecologist at University College London, has been working to improve ovarian cancer diagnosis since the mid-90s. Specifically, she’s worked to pick up ovarian cancers earlier, when treatment is more likely to be successful.

The benefits of earlier diagnosis are clear – around 90 in 100 women diagnosed with early-stage ovarian cancer survive for 5 years or more, compared with just 3 in 100 women with late-stage disease.

But spotting ovarian cancer early enough to make a difference is difficult. Symptoms can be vague and are usually shared with other, more common, and often less serious, conditions.

To try and make the shift needed, Menon and others looked to screening.

In 1999, Menon joined Professor Ian Jacobs’ team and together they set up the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).

20 years later, the results are in.

Putting ovarian screening to the test

In the 80s and 90s, researchers were hunting for tests that could pick up ovarian cancer earlier.

Two strategies seemed to hold promise – one based on ultrasound and the other looking at changes in the levels of a protein called CA125 in the blood. Jacobs and Menon selected these to put to the test in a large, randomised control trial.

Alongside other organisations, our forerunners funded UKCTOCS. The goal – to prove if either approach could save lives from ovarian cancer.

The trial involved 202,000 women aged 50 to 74 across the country:

  • Half the women formed the ‘control’ group and weren’t given any screening.
  • A second group were given a yearly ultrasound scan to look for abnormalities in the ovaries that could be a sign of cancer.
  • A third group were given an annual blood test to measure their CA125 levels.

CA125 levels are often raised in women with ovarian cancer. But as levels can vary between women, the team developed a more sophisticated approach, measuring how each woman’s CA125 levels change over time. They called the approach the ‘Risk of Ovarian Cancer Algorithm’ (or ROCA, for short).

After each blood test, ROCA generated a risk-related score that would affect what happened next:

  • Women with ‘normal’ ROCA scores continued with annual screening.
  • Those at ‘intermediate risk’ had another blood test 3 months later.
  • Those at ‘elevated risk’ had another blood test and an ultrasound within 6 weeks.

The ROCA test is now available privately. Several of those running the trial – along with Cancer Research UK (via our technology transfer company, Cancer Research Technology) – receive a proportion of proceeds from its sale.

The trial recruited women from 2001 to 2005, with yearly screening continuing until 2011. Then it was a waiting game.

It takes a long time to determine whether screening affects deaths from the disease, so the researchers had to follow the participants up until 2020 to be sure if there was the impact or not.

Graphic showing the different arms of the UKCTOCS trial.

Copy this link and share our graphic. Credit: Cancer Research UK

What did UKCTOCS find?

The ultrasound screening strategy wasn’t able to detect ovarian cancers earlier or save lives.

However, data from the blood test group was more interesting.

“What we found is with the strategy that used the blood test, we did pick up women with ovarian cancer earlier than in the control group where women had no screening. But in both screening groups we were not able to save lives.”

In the blood test group, the incidence of early stage (1 or 2) ovarian cancer was 39% higher than in the no screening group which is a promising indicator. But this isn’t enough to show the benefit of screening – the balance of a range of benefits and harms must be taken into account.

The most important target for a screening strategy is reducing deaths from the disease. And unfortunately, this goal was not met.

For Menon and the team, the results were deeply disappointing. Menon thinks there are a few reasons that despite promising signs, the CA125 blood test strategy didn’t ultimately save lives. “We didn’t pick up enough women early and we didn’t pick up cancers early enough.”

The team also noticed that women who were picked up earlier didn’t seem to respond to the standard treatment as expected. They’re looking at this data in more detail now.

“What we need to do now is to analyse very carefully what treatment people on the trial received. And there are a lot of insights that I think the trial can provide.”

An enduring legacy

All women who took part donated their data and blood samples for researchers to use in secondary studies. And in the group 50,000 women who had yearly blood tests, this has created an extremely rich resource. “What we have is a very unique set of annual samples spanning 7 to 11 plus years,” says Menon.

The team look forward to “using and sharing the data and the samples with researchers the world over. So that we don’t leave any stone unturned and we learn everything we can.”

For the women who were diagnosed with ovarian cancer during the study, these blood tests offer a snapshot into what was happening in the years leading up to diagnosis.

Menon says these samples are already being used to evaluate promising new tests coming through. “We have the ability to use this bank and the earlier samples to see if new tests could have performed better than CA125 and ROCA.” This data will be invaluable in guiding future trials.

The data also provide a unique opportunity to study how ovarian cancer develops, something Menon is keen to explore further. “We’re hoping that people who do natural history modelling will use this data to try and understand more about ovarian cancer.”

This knowledge could lay the groundwork for new approaches. Because as Menon points out “all our attempts for early detection are based on understanding the disease better”.

And it doesn’t stop with ovarian cancer.

Beyond ovarian cancer

“There were also women who took part who were diagnosed with other cancers – breast cancer, bowel cancer – as well as other diseases. And because they were willing to share their data and samples with researchers, we also have lots of groups who are working on early detection of other cancers using the UKCTOCS samples.”

These samples are a crucial part of the legacy of UKCTOCS, which will help guide future studies. “It’s a very rich resource for which we are hugely grateful to the women for sharing with the wider world.”

Menon says another legacy of the trial is to reaffirm how important it is to look at lives saved in big screening programmes.

“If we had just focused on early detection and what percentage of women are diagnosed at stage 1 or 2, we might have got the wrong answer. That’s why we followed everybody for so long – we needed to find out if diagnosing women earlier will translate into lives saved, but it didn’t.”

The road ahead

While the trial involved many from what Menon calls the ovarian cancer community, it’s not been the only focus for the community.

“There’s a lot of efforts focused on symptomatic women – trying to decrease diagnosis at advanced stage and the number of women diagnosed through A&E.”

There have also been many improvements in ovarian cancer treatment in the last decade.

Spotting ovarian cancer

Symptoms of ovarian cancer can be quite vague and similar to symptoms caused by less serious conditions, which can make spotting the disease tricky. If you notice unusual or persistent changes, talk to your doctor.

Whether it’s needing to go to the toilet more often, pain, bloating, or something else, raise it with your GP – in most cases it won’t be cancer but it’s best to get it checked out.

Researchers are also looking into better risk management strategies for high-risk women.

“In UKCTOCS, we tested screening in the general population. But there’s a small group who are at an increased risk of ovarian cancer because they have a genetic mutation.” For these women, studies are exploring how to refine risk reducing surgery, as well as more frequent screening.

It’s been a long road for Menon and the UKCTOCS team and they’re not done yet. Looking back on the last two decades, Menon says the team are indebted to the women who took part and to everyone who supported the trial.

“I think we can be proud of the effort – it was a huge trial spanning 20 years. Everyone came together and supported it. It’s a testament to the research that can be done in the NHS.”

Katie 


    Comments

  • Yvonne
    21 October 2021

    I was in the UKCTOCS screeing having my bloods taken & received a thank you card at the end. ln 2014 I had a pain which I thought maybe gallstones. I went to the GP eventually had an appointment in July for an ulntrasound scan. At the scan I asked could she scan further as I was bloated. I had hodgekin’s diesease in 1983. With no MRI’s I had to have my spleen out as a test. My ovaries were put behind my uterus ‘to protect them’ as I was young. I thought I might have very large cysts on my ovaries or cancer! She was interested, so said she will have a look. She saw nothing [probably because just a scan and ovearies behind uterus]. She said I will be called in about 6 months for another scan to see if gall stones changed [I am still waiting]. With the bloating I went back to the GP. He did blood tests and phoned me the next evening. he said all okay. I said what about the bloating. He said lay off cakes & biscuits! . Never going to a GP unles I can’t cure myself I could not get an appointment. I had to tell a lie and say I was in pain to be seen at a walk in surgery there. I was told I was heavily constipated to the large bowel?? I go to the toilet every day and do not have overflow or any problems. With 10 days of powders i was frightened to leave the loo. Still looking now 10 months pregnant I tried to get an appointment. “It will be 5 weeks time, as we do our diary tomorrow, but you can have a phone appointment”.. That was with a lady GP who comes in once a week. She phoned right on time and I relayed quickly what I thought. She said you are really worried, I said no, I think I am seriously ill. She booked me in for bloods monday plus a celiac blood test and an appointment with her the next Thursday. When I arrived Thursday she said you knew, didn’t you. My C125 level was just under 2,000. Yes two thousand.

  • Jan
    19 September 2021

    I’ve just completed a year’s worth of ultrasounds due to the discovery of a growing ovarian cyst. As I understand it the problem is that ovarian cancer is often discovered too late. However, as I have no adverse symptoms the scans have stopped and nobody is doing anything. So what next, a burst cyst, cancer?

  • Sandra MacIver
    18 September 2021

    Sorry to read the negative stories below. I was diagnosed in January 2021, in the middle of all the Covid stuff. I have had a hysterectomy and have 1 round of chemo left. I am hopeful I can use the word free by the end of October. I know I have been lucky to have a good GP team and then so much support from the Spey Unit at Dr Grays Hospital in Elgin.

  • Gail Maden
    18 September 2021

    I had ovarian cancer when i was 38, i am now 69, i thought i was putting on weight, but grew from a flat tummy to the size of a full term pregnancy in 6 days. I had a 5lb tumour removed the size of a rugby ball. I was so lucky to have a brilliant surgeon. 10 years later i had the other overy removed because of a cist on it.

  • Elizabeth Ogden
    18 September 2021

    I think the last sentence says it all. Without our NHS this kind of research will not take place.

  • Maureen Renshaw
    17 September 2021

    My daughter died of this 9 years ago she was 34 a test is needed to catch it early

  • Alison Spencer
    17 September 2021

    I’m sure the research is well justified. Sadly it isn’t yet enough. One of my friends was picked up early in this trial. She sadly died. But all research helps and one day there will be a breakthrough.

  • Sheena Macleod
    16 September 2021

    Felt quite tearful.reading this ,it is my biggest fear as I watched my mother have to try and live with this at the same time as I was diagnosed with Breast cancer …….
    My oncologist is convinced there is a genetic factor within my mothers family for predisposing of cancer (a high incidence of Cancer and some other ovarian cancer ladies ) however genetics have done all they can but cannot find it yet …
    So although I want an oopherectomy no professional will make the decision ….
    I hope the research keeps moving forward and more understanding of detection early and treatment

  • Helen Taylor
    16 September 2021

    Thankyou for all the scientists. Glad they are researching, sad no clear benefits. My mum visited GP for years with bloating, pain etc etc. Told it was stress , IBS. She read a leaflet in surgery in 2009 about ovarian cancer and asked for investigation .GP agreed and thought it highly unlikely. She was right, stage 4.She died 2010 .
    Glad education is improving, slowly.

  • Bridie Reidy
    15 September 2021

    I think this is the first stage of research and that the data you hold and share with colleagues worldwide will be helpful in getting on top of this sooner because of your efforts. Well done.

  • Margaret Evans
    13 September 2021

    I was diagnosed with ovarian cancer in December 2019. I had been attending my Gp for 12 months with pain, they said it was IBS!!! The advanced nurse practitioner sent me for a CA 125 blood test and it was all go from there. Two major surgeries and 8 rounds of Chemotherapy I’m taking Parp inhibitors and thanks to the nurse I’m still here. I also found out I have the faulty Gene.

  • Peter McLoughlin
    30 May 2021

    Probably because you caught cases early with stage 1 & 2 you didn’t follow an aggressive treatment. Especially with stage 1 if you went for an aggressive hysterectomy you might get a far better result

  • B. Dutton
    26 May 2021

    I took part in the screening tests and it was a disappointing result, but hopefully, a cure will be found in the not too distant future..

  • Melanie R. Palomares, M.D., M.S.
    19 May 2021

    I’d love to see QOL and health economics data. As cancer therapeutics continue to improve, I would expect it to only become more difficult to demonstrate a survival benefit over time.

  • Dr Madhuri Gawande
    14 May 2021

    I still think that there has to be a good screening test for ovarian cancer. If by screening the women are picked up in early stage and five year survival is good then isn’t it sufficient to implement screening for ovarian cancer regularly??

  • reply
    Katie Roberts
    20 May 2021

    Dear Madhuri,

    Thanks for your question.

    In order to implement a screening programme, there needs to be evidence that the screening test saves lives.

    Even though the UKCTOCS trial detected some ovarian cancers earlier, it didn’t have an impact on how many women died from ovarian cancer – there was no survival difference between the screening group and control at any point in the trial (5,10, 15 or 18 years). It did not save lives and so doesn’t meet the main criteria for introducing a screening programme.

    This means that screening women for ovarian cancer using this test would expose individuals to the potential harms of screening without any benefit.

    However, this doesn’t mean that a good screening test for ovarian cancer won’t exist in the future and research will continue to look for new tests and treatment.

    Best wishes,

    Katie, Cancer Research UK

    Comments

  • Yvonne
    21 October 2021

    I was in the UKCTOCS screeing having my bloods taken & received a thank you card at the end. ln 2014 I had a pain which I thought maybe gallstones. I went to the GP eventually had an appointment in July for an ulntrasound scan. At the scan I asked could she scan further as I was bloated. I had hodgekin’s diesease in 1983. With no MRI’s I had to have my spleen out as a test. My ovaries were put behind my uterus ‘to protect them’ as I was young. I thought I might have very large cysts on my ovaries or cancer! She was interested, so said she will have a look. She saw nothing [probably because just a scan and ovearies behind uterus]. She said I will be called in about 6 months for another scan to see if gall stones changed [I am still waiting]. With the bloating I went back to the GP. He did blood tests and phoned me the next evening. he said all okay. I said what about the bloating. He said lay off cakes & biscuits! . Never going to a GP unles I can’t cure myself I could not get an appointment. I had to tell a lie and say I was in pain to be seen at a walk in surgery there. I was told I was heavily constipated to the large bowel?? I go to the toilet every day and do not have overflow or any problems. With 10 days of powders i was frightened to leave the loo. Still looking now 10 months pregnant I tried to get an appointment. “It will be 5 weeks time, as we do our diary tomorrow, but you can have a phone appointment”.. That was with a lady GP who comes in once a week. She phoned right on time and I relayed quickly what I thought. She said you are really worried, I said no, I think I am seriously ill. She booked me in for bloods monday plus a celiac blood test and an appointment with her the next Thursday. When I arrived Thursday she said you knew, didn’t you. My C125 level was just under 2,000. Yes two thousand.

  • Jan
    19 September 2021

    I’ve just completed a year’s worth of ultrasounds due to the discovery of a growing ovarian cyst. As I understand it the problem is that ovarian cancer is often discovered too late. However, as I have no adverse symptoms the scans have stopped and nobody is doing anything. So what next, a burst cyst, cancer?

  • Sandra MacIver
    18 September 2021

    Sorry to read the negative stories below. I was diagnosed in January 2021, in the middle of all the Covid stuff. I have had a hysterectomy and have 1 round of chemo left. I am hopeful I can use the word free by the end of October. I know I have been lucky to have a good GP team and then so much support from the Spey Unit at Dr Grays Hospital in Elgin.

  • Gail Maden
    18 September 2021

    I had ovarian cancer when i was 38, i am now 69, i thought i was putting on weight, but grew from a flat tummy to the size of a full term pregnancy in 6 days. I had a 5lb tumour removed the size of a rugby ball. I was so lucky to have a brilliant surgeon. 10 years later i had the other overy removed because of a cist on it.

  • Elizabeth Ogden
    18 September 2021

    I think the last sentence says it all. Without our NHS this kind of research will not take place.

  • Maureen Renshaw
    17 September 2021

    My daughter died of this 9 years ago she was 34 a test is needed to catch it early

  • Alison Spencer
    17 September 2021

    I’m sure the research is well justified. Sadly it isn’t yet enough. One of my friends was picked up early in this trial. She sadly died. But all research helps and one day there will be a breakthrough.

  • Sheena Macleod
    16 September 2021

    Felt quite tearful.reading this ,it is my biggest fear as I watched my mother have to try and live with this at the same time as I was diagnosed with Breast cancer …….
    My oncologist is convinced there is a genetic factor within my mothers family for predisposing of cancer (a high incidence of Cancer and some other ovarian cancer ladies ) however genetics have done all they can but cannot find it yet …
    So although I want an oopherectomy no professional will make the decision ….
    I hope the research keeps moving forward and more understanding of detection early and treatment

  • Helen Taylor
    16 September 2021

    Thankyou for all the scientists. Glad they are researching, sad no clear benefits. My mum visited GP for years with bloating, pain etc etc. Told it was stress , IBS. She read a leaflet in surgery in 2009 about ovarian cancer and asked for investigation .GP agreed and thought it highly unlikely. She was right, stage 4.She died 2010 .
    Glad education is improving, slowly.

  • Bridie Reidy
    15 September 2021

    I think this is the first stage of research and that the data you hold and share with colleagues worldwide will be helpful in getting on top of this sooner because of your efforts. Well done.

  • Margaret Evans
    13 September 2021

    I was diagnosed with ovarian cancer in December 2019. I had been attending my Gp for 12 months with pain, they said it was IBS!!! The advanced nurse practitioner sent me for a CA 125 blood test and it was all go from there. Two major surgeries and 8 rounds of Chemotherapy I’m taking Parp inhibitors and thanks to the nurse I’m still here. I also found out I have the faulty Gene.

  • Peter McLoughlin
    30 May 2021

    Probably because you caught cases early with stage 1 & 2 you didn’t follow an aggressive treatment. Especially with stage 1 if you went for an aggressive hysterectomy you might get a far better result

  • B. Dutton
    26 May 2021

    I took part in the screening tests and it was a disappointing result, but hopefully, a cure will be found in the not too distant future..

  • Melanie R. Palomares, M.D., M.S.
    19 May 2021

    I’d love to see QOL and health economics data. As cancer therapeutics continue to improve, I would expect it to only become more difficult to demonstrate a survival benefit over time.

  • Dr Madhuri Gawande
    14 May 2021

    I still think that there has to be a good screening test for ovarian cancer. If by screening the women are picked up in early stage and five year survival is good then isn’t it sufficient to implement screening for ovarian cancer regularly??

  • reply
    Katie Roberts
    20 May 2021

    Dear Madhuri,

    Thanks for your question.

    In order to implement a screening programme, there needs to be evidence that the screening test saves lives.

    Even though the UKCTOCS trial detected some ovarian cancers earlier, it didn’t have an impact on how many women died from ovarian cancer – there was no survival difference between the screening group and control at any point in the trial (5,10, 15 or 18 years). It did not save lives and so doesn’t meet the main criteria for introducing a screening programme.

    This means that screening women for ovarian cancer using this test would expose individuals to the potential harms of screening without any benefit.

    However, this doesn’t mean that a good screening test for ovarian cancer won’t exist in the future and research will continue to look for new tests and treatment.

    Best wishes,

    Katie, Cancer Research UK