Published: 13 May 2021
A large-scale randomised trial of annual screening for ovarian cancer, funded by the NIHR, did not succeed in reducing deaths from the disease, despite one of the screening methods tested detecting cancers earlier.
Results from the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) have been published in a report in the medical journal The Lancet.
In the UK, 4,000 women die from ovarian cancer each year. It is not usually diagnosed until it is at a late stage and hard to treat. UKCTOCS 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 latest analysis looked at data from more than 200,000 women aged 50-74 at recruitment who were followed up for an average of 16 years. The women 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 researchers found that, while the approach using multimodal testing succeeded in picking up cancers at an early stage, neither screening method led to a reduction in deaths.
Earlier detection in UKCTOCS did not translate into saving lives. Researchers said this highlighted 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.”
Women aged between 50 and 74 were enrolled in the trial between 2001 and 2005. Screening lasted until 2011 and 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.
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.
The initial analysis of deaths in the trial occurred in 2015, but there was not enough data at that time to conclude whether or not screening reduced deaths. By looking at five more years of follow up data from the women involved, researchers are now able to conclude that the screening did not save lives.
A huge wealth of samples and data from the trial has been donated by the participants for future research. This resource, referred to as the UKCTOCS Longitudinal Women’s Cohort (UKLWC), is now being used by researchers worldwide, helping to improve understanding of ovarian cancer as well as other cancers and other diseases such as cardiovascular disease.
Researchers say that 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. These insights will be helpful to future trials in all areas of health. It 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.
Professor Nick Lemoine, Medical Director, NIHR Clinical Research Network, said: “These important findings from a large-scale trial, involving 200,000 participants, show that annual screening did not succeed in reducing deaths from ovarian cancer.
“However, it’s important to note that negative results can be as important as positive. The study has provided important new evidence and insights into how to conduct and analyse future large-scale randomised clinical trials into ovarian cancer, in the hope that this will prevent and diagnose this disease more effectively in the future.
"We thank every single person who took part.”
The project was funded by the NIHR Health Technology Assessment (HTA) Programme. For more details, please see the project page.