A trial of ovarian cancer screening has shown that it did not succeed in reducing ovarian cancer deaths, despite one of the methods detecting cancer at an earlier stage.
The large-scale, randomised UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) looking at annual screening for ovarian cancer, led by researchers at University College London (UCL), has shown that various screening methods did not lead to a reduction in deaths from ovarian cancer.
In the UK, 4,000 women die from ovarian cancer each year, and the disease is not usually diagnosed until it is at a late stage and hard to treat. The trial was designed to test the hypothesis that a reliable screening method that picks up ovarian cancer earlier, when treatments are more likely to be effective, could save lives. The results have been published in The Lancet.
Screening is not reducing deaths
The analysis looked at data from more than 200,000 women aged 50 to 74 at recruitment who were followed up for an average of 16 years. They were randomly allocated to one of three groups: no screening, annual screening using an ultrasound scan, and annual multimodal screening involving a blood test followed by an ultrasound scan as a second line test.
The team found that using multimodal testing succeeded in picking up cancers at an early stage, however, neither screening method led to a reduction in deaths. The researchers say this highlights the importance of requiring evidence that any potential screening test for ovarian cancer actually reduced deaths, as well as detecting cancers earlier.
Professor Usha Menon (MRC Clinical Trials Unit at UCL), lead investigator of UKTOCS, said: “UKCTOCS is the first trial to show that screening can definitely detect ovarian cancer earlier. However, this very large, rigorous trial shows clearly that screening using either of the approaches we tested did not save lives. We therefore cannot recommend ovarian cancer screening for the general population using these methods.
“We are disappointed as this is not the outcome we and everyone involved in the trial had hoped and worked for over so many years. To save lives, we will require a better screening test that detects ovarian cancer earlier and in more women than the multimodal screening strategy we used.”
Screening methods
Women aged between 50 and 74 were enrolled in the trial between 2001 and 2005 and screening lasted until 2011 – which was either an annual blood test, monitoring changes in the level of the protein CA125, or a yearly vaginal ultrasound scan. About 100,000 women were assigned to the no screening group, and more than 50,000 women to each of the screening groups.
The analysis found that blood test screening picked up 39% more cancers at an early stage (Stage I/II), while detecting 10% fewer late-stage cancers (Stage III/IV) compared to the no screening group. There was no difference in the stage of cancers detected in the ultrasound group compared to the no screening group.
Professor Mahesh Parmar, Director of the MRC Clinical Trials Unit at UCL and a senior author on the paper, said: “There have been significant improvements in the treatment of advanced disease in the last 10 years, since screening in our trial ended. Our trial showed that screening was not effective in women who do not have any symptoms of ovarian cancer; in women who do have symptoms early diagnosis, combined with this better treatment, can still make a difference to quality of life and, potentially, improve outcomes. On top of this, getting a diagnosis quickly, whatever the stage of the cancer, is profoundly important to women and their families.”
Professor Ian Jacobs, from the University of New South Wales (UNSW Sydney), a co-investigator who has led the ovarian cancer screening research programme since 1985 and lead investigator of UKCTOCS from 2001-2014, said: “My thanks to the thousands of women, healthcare professionals and researchers who made this trial possible. The multimodal screening strategy did succeed in detection of ovarian cancer at an earlier stage, but sadly that did not save lives. This is deeply disappointing and frustrating given the hope of all involved that we would save the lives of thousands of women who are affected by ovarian cancer each year.
“Population screening for ovarian cancer can only be supported if a test is shown to reduce deaths in a future randomised controlled trial. I remain hopeful that a new effective screening test will be found eventually, but it will take many years to conduct a large trial of the test. Realistically, this means we have to reluctantly accept that population screening for ovarian cancer is more than a decade away.”
A huge wealth of samples and data from the trial has been donated by the participants for future research, which is being used by researchers worldwide to improve understanding of ovarian cancer as well as other cancers and other diseases such as cardiovascular disease.
The study has also generated insights into how best to design, conduct, and analyse a large-scale randomised clinical trial particularly in individuals who have no signs of disease and has also contributed to advances in risk assessment, prevention, and diagnosis of ovarian cancer.
The UKCTOCS trial was funded by the NIHR Health Technology Assessment (HTA) Programme and the charities Cancer Research UK and The Eve Appeal.
