‘Disappointing’ Mortality Outcomes Shown For Ovarian Cancer Screening Trial

Author: By Lynda Williams, Senior medwireNews Reporter 

medwireNews: A multimodal screening strategy improved detection of ovarian and tubal cancer at an early stage of disease but this has not translated to a significant decrease in mortality rates over 16 years of follow-up, say the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) investigators. 

“While disappointing, the trial has provided a clear answer that our screening strategies coupled with treatment protocols available in 2001–11 (the active screening phase) did not save lives”, write Usha Menon, from University College London in the UK, and co-authors in The Lancet. 

“Currently, general population screening for ovarian and tubal cancer cannot be recommended”, they state. 

Overall, 50,625 women aged 50–74 years in England, Wales and Northern Ireland were randomly assigned to receive a multimodal risk-stratified screening protocol, consisting of the Risk of Ovarian Cancer Algorithm and annual CA125 testing with second-line repeat CA125 testing and transvaginal ultrasound screening (USS). 

An additional 50,623 women received an annual USS only and 101,314 women received no screening, the researchers explain. 

The women in the screening cohorts underwent a median of eight annual screens and follow-up to censorship or death was conducted for 95.0% of the participants, resulting in 3.16 million woman–years of follow-up. 

After a median 16.3 years, tubal or ovarian cancer was detected in 1.0% of all three cohorts – indicating that screening is not associated with a risk of overdiagnosis – and 0.6% of each group died from the disease. 

Nor was there a difference in the mortality rates between the cohorts when looking only at the outcomes of women diagnosed with invasive epithelial ovarian and tubal cancers, with a 0.6% death rate in all three cohorts. 

The investigators note that, 9.5 years after screening ended, women who received multimodal screening had a 47.2% increase in the incidence of stage I disease diagnosis and a 24.5% reduction in the incidence of stage IV disease diagnosis compared with non-screened women. 

And there was a 39.2% increase in stage I–II disease and a 10.2% decrease in the incidence of stage III–IV disease with the multimodal protocol versus no screening.  

Usha Menon et al believe that the lack of mortality benefit despite these changes in stage distribution emphasizes “the importance of having disease-specific mortality as the primary outcome in ovarian cancer screening trials.”  

Of concern, women in the multimodal screening group had a higher rate of ovarian and tubal mortality from stage I disease than the no-screening counterparts (14.8 vs 9.4%) accompanied by a lower rate of stage IV disease mortality (79.5 vs 83.7%), promoting the investigators to write it “seems probable that the cancers shifted to an earlier stage had an intrinsic poor prognosis, which was not altered by earlier detection and the available treatments for early stage disease.” 

Noting that “there have been substantial advances in the treatment of advanced disease in the past 10 years since the end of screening in Dec 31, 2011”, the team says that planned data analyses may help to determine whether “advances in treatment, in combination with earlier diagnosis could contribute to better quality of life and improved outcomes.” 

Discussing the future of ovarian cancer screening, the authors of a linked comment acknowledge that there have also been improvements in imaging since the UKCTOCS study began and identification of “promising biomarkers” that could be tested as screening tools, such as circulating tumour DNA, DNA methylation or autoantibodies. 

But they postulate that “alternative approaches to screening that target women at higher risk as opposed to the general population might prove more effective at reducing ovarian cancer deaths and could lessen the harm from false positive screens, as has been exemplified by lung cancer screening.” 

Regardless, Lauren Hurwitz, from the National Cancer Institute in Rockville, Maryland, USA, and co-commentators conclude that “screening for ovarian cancer remains elusive but is not a lost cause; there is simply much more work to be done.” 

References  

Menon U, Gentry-Maharaj A, Burnell M, et al. Ovarian cancer population screening and mortality after long-term follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet; Advance online publication 12 May 2021. DOI: 10.1016/ S0140-6736(21)00731-5 

Hurwitz LM, Pinsky PF, Trabert B. General population screening for ovarian cancer. Lancet; Advance online publication 12 May 2021. DOI:10.1016/ S0140-6736(21)01061-8