'25 at 25': Ovarian cancer screening: The UKCTOCS trial

05 Feb 2024

To celebrate the 25^th anniversary of the MRC Clinical Trials Unit and World Cancer Day, we highlight our work throughout the past two decades to help detect ovarian cancer earlier. This article is part of a series highlighting 25 major achievements from the 25 years since the MRC CTU at UCL was formed. It focuses on UKCTOCS, the largest screening trial ever in ovarian cancer.

Around 4,000 women die from ovarian cancer in the UK each year. Usually, this type of cancer is not diagnosed until it is at a late stage and hard to treat. To improve screening approaches and pick up ovarian cancer earlier, we ran the UK Collaborative Trial of Ovarian Cancer Screening or UKCTOCS trial.

Between 2001 and 2020, more than 200,000 women from England, Wales and Northern Ireland took part in UKCTOCS. Researchers tested two screening approaches to see if they could detect ovarian cancer earlier, when symptoms are yet to appear and treatments are more likely to be effective and save lives. Researchers screened participants using either an ultrasound scan, or multimodal screening involving monitoring changes in blood levels of a cancer marker followed by an ultrasound scan. They compared these groups to a no-screening group.

After following up these women for an average of 16 years, the UKCTOCS researchers found that, while the multimodal screening could pick up cancers earlier, neither of the two screening approaches were able to reduce deaths compared with no screening. These were disappointing results for everyone. However, the robustness of the trial and the quality of the data clearly demonstrated that ovarian cancer screening for the general population cannot be recommended using these two screening approaches.

Exploratory analyses undertaken after the trial have shown that the multimodal approach detected the most lethal type of ovarian cancer – high-grade serous cancer – earlier, leading to women in this group living longer. This suggests that new tests in the pipeline that can pick up more women with this type of cancer earlier could save lives in the future. The data from women who had their cancer detected earlier is being used to identify early symptoms that could indicate the possibility of ovarian cancer.

As part of the trial, a huge wealth of samples and data was donated by the participants for future research. This resource is referred to as the UKCTOCS Longitudinal Women’s Cohort (UKLWC). The UKLWC is already being used by researchers worldwide to improve our understanding of ovarian cancer and to evaluate new tests for early detection of ovarian as well as other cancers and conditions such as cardiovascular disease.

Designing and running such a large and lengthy trial came with its own challenges. These included recruiting all the participants on time, keeping them engaged during the years they were part of the trial, providing over half a million annual ultrasound scans and blood tests, and collecting and analysing the data accurately. To share the lessons learned, the team has published multiple papers and an extensive report describing the key challenges that UKCTOCS faced in its design, conduct and analysis. We have also produced a podcast episode where we talk to Usha Menon to discuss the key learnings captured in the report.

UKCTOCS was funded by the MRC, NIHR HTA Programme, the EME Programme (an MRC and NIHR partnership), and Cancer Research UK and The Eve Appeal.

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