The long term follow-up, funded by National Institute for Health Research (NIHR) together with CR UK and The Eve Appeal has now completed. The final results were published in The Lancet on 12th May 2021. (Click here for the link to the full text article)
Screening for ovarian cancer does not lead to a reduction in deaths, a Lancet study has found, ending hopes of saving more lives through a national programme.
Around 4,000 women die from ovarian cancer every year in the UK, with the disease more often diagnosed at a late stage meaning it is harder to treat.
The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), which began screening women in 2001, tested the theory that reliable screening that picks up ovarian cancer early could save lives.
But data gathered from more than 200,000 women over an average of 16 years suggested screening the general population “cannot be recommended”, the experts said.
The women were randomly allocated to three groups; no screening, annual screening using an ultrasound scan, and annual multimodal screening involving a blood test.
Blood test screening - which monitored changes in the level of the protein CA125 - picked up almost two fifths of early stage cancers, but detected 10 per cent fewer late-stage cancers compared with the no-screening group.
No difference in the stage of cancers was detected between the ultrasound group and the no-screening group.
Despite finding more early stage cancers in the multimodal group there was "no evidence of a difference over a reduction in ovarian cancer deaths in the multimodal or ultrasound groups compared to the no-screening group", Prof Mahesh Parmar, director of the MRC Clinical Trials Unit at UCL and a senior author on the paper, said.
"We cannot recommend general population screening for ovarian cancer for routine practice," he added.
Prof Usha Menon, lead investigator at the UKCTOCS, said: “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.”
Currently, there is no national screening programme for ovarian cancer on the NHS and the results of the trial were expected to inform any decision to create one.
Asked why screening did not lead to a reduction in deaths, Prof Parmar told reporters that more women needed to be identified at an early stage.
He added: “This disease is such that even if you did that... it's going to be aggressive whatever you do.
"Even if you find it at an early stage, there is an indication that (death) might be the case for some women and if that is the case that would be very depressing indeed".
Participants in the trial, who were aged between 50 and 74, were enrolled between 2001 and 2005, and screened until 2011.
The initial analysis of deaths in the trial occurred in 2015, but there was not enough data at that time to conclude whether screening reduced deaths so it was decided to do five more years of follow-up data.
Prof Menon said since 2011 there had been “significant advances” in treatments for ovarian cancer. But Prof Parmar added those advances had been for late-stage cancers with “relatively little change” for early-stage cancers.
Ovarian cancer screening for women over 50 could save lives
The results of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), a 14-year trial coordinated from UCL and the largest ever trial of ovarian cancer screening are published in the Lancet today. The results suggest that annual screening for ovarian cancer using a specialised algorithm may save lives.
At present a quarter of a million women worldwide develop ovarian cancer each year and more than half (140,000) die from the disease, despite extensive surgery and chemotherapy. The initial estimates of the relative reduction in deaths achievable through screening in UKCTOCS, range from 15% to 28%. This suggests between 75 and 150 deaths could be prevented each year for every million women aged 50-74 invited for screening. For each woman found to have ovarian cancer, 2-3 additional women would need to undergo surgery as a result of an abnormal screen and found to have non-cancerous ovarian lesions.
"I am excited that UKCTOCS provides the first evidence ever produced to suggest that early detection by screening may save lives" said Ian Jacobs, Honorary Professor UCL and President/Vice Chancellor of UNSW Australia. "This brings hope to a disease for which the outlook is poor and has not improved much during the last three decades".
Usha Menon, UCL Professor who leads the Gynaecology Cancer Research Unit said: "UKCTOCS has been an immense research effort spanning 15 years, involving 202,000 women and 700,000 annual screens. Finally we have data which suggests that screening may prevent ovarian cancer deaths. This is welcome news and provides fresh impetus for renewed efforts in this area.’’
UKCTOCS was funded jointly by the Medical Research Council, Cancer Research UK, National Institute of Health Research and The Eve Appeal. The trial involved 202,638 post-menopausal women aged 50 or over who were randomly assigned to either annual multimodal screening using the Risk of Ovarian Cancer Algorithm (ROCA), annual transvaginal ultrasound, or no test. ROCA uses a statistical calculation to interpret changing levels in women’s blood of a protein called CA125, which is linked to ovarian cancer.
1,282 women were diagnosed with ovarian cancer since the start of the study in 2001, of whom 649 had died of the disease by December 2014. The impact of screening on reducing ovarian cancer deaths was assessed in several ways. The pre-planned and most cautious analysis estimated a 15% relative reduction in deaths which did not reach conventional levels of statistical significance. However, further analysis showed that this effect appeared to increase over time, rising from an 8% relative reduction in the number of deaths in the first seven years to a 23% relative reduction in the following seven years. The most encouraging pre-planned analysis, which excluded patients with evidence of ovarian cancer before screening commenced, estimated that screening would reduce deaths by 28%. Overall, the long-term effect of a multimodal screening programme may be of the order of 20%. Further follow-up in UKCTOCS during the next 3 years is needed to clarify the extent of the reduction in deaths achieved by screening.
The estimate of ovarian cancer mortality reduction in UKCTOCS is similar to that observed in randomised breast cancer screening trials where estimates vary from 15% to 25%. For 1000 women invited to biennial mammography screening for 20 years from age 50, it is estimated that 2-3 deaths from breast cancer are prevented. Preliminary estimates for UKCTOCS suggest that for 1000 women screened annually using the multimodal strategy for 14 years in the trial, 1-2 ovarian cancer deaths are prevented.
Ovarian cancer: Setback as major screening trial fails to save lives (BBC News web pages; Wed 12 May 2021)
Annual screening for ovarian cancer does not save lives, study finds (The Guardian; Wed 12 May 2021)
Screening for ovarian cancer is ruled out after trial found it did not reduce deaths (BMJ; Wed 12 May 2021)
A trial looking at screening the general population for ovarian cancer (UKCTOCS) (CRUK website; May 2021)