The results of a huge British trial involving more than 200,000 women who were followed for an average of 16 years have been negative. The researchers found that annual monitoring of ovarian cancer with multimodal screening (MMS) or transvaginal ultrasound screening (USS) did not reduce the number of deaths from this aggressive cancer, although MMS chose the disease in its early stages.
“We are disappointed as this is not the result that each and every person involved in the trial had expected and worked on for so many years,” commented Usha Menon, MD, MRC Clinical Trials Unit (MCT), Institute of clinical trials and methodology, London, UK, and principal investigator of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
“UKCTOCS is the first trial that shows that screening can detect ovarian cancer definitely before. However, this very large and rigorous trial clearly shows that screening with any of the methods we tested did not save lives,” he said. say in a statement.
“Therefore, we cannot recommend the detection of ovarian cancer for the general population using these methods,” he added.
Echoing these sentiments, coin researcher Jacobs, MD, of the University of New South Wales, Sydney, Australia, who led the UKCTOCS from 2001 to 2014, acknowledged that while the ‘MMS was able to detect ovarian cancer at an earlier stage of the disease this 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 affected by ovarian cancer each year,” she added in a statement.
The study was published online May 12 The Lancet.
At a UK press conference, Menon stressed that ovarian cancer is an aggressive disease, with a 10% to 10% survival. It is difficult to diagnose and more than half of the cases are diagnosed when the disease is in its final stages.
Because screening cannot be recommended at this time, he urged women and doctors to be alert and not ignore symptoms that may suggest ovarian cancer.
NHS Trust Recruitment
The trial included a total of 202,562 assessable postmenopausal women aged 50 to 74 who were recruited through the National Health Service (NHS) Trust in England, Wales and Northern Ireland.
Women were randomly assigned to receive no screening, annual screening with ultrasound, or annual MMS involving a CA125 blood test followed by an ultrasound. The main result was death from ovarian or fallopian tube cancer.
At a mean follow-up of 16.3 years, the incidence and mortality from ovarian and fallopian tube cancer were identical in the three groups, with 1.0% for the incidence of ovarian and fallopian tube cancer. 0.6% risk of death.
The end results were perhaps even more disappointing, as there was evidence from the trial that the MMS detected a disease at an earlier stage, for which survival rates are better.
At 9.5 years after the end of screening, there was a 47.2% higher incidence of stage I disease in the MMS group compared to the non-screening group, as well as a 24.5% lower incidence. of disease in stage IV.
Overall, there was a 39.2% higher incidence of stage I or II cancer and a 10.2% lower incidence of stage III or IV cancer in the MMS group compared with group without screening. There were few changes in the incidence of stage III disease.
There were also no differences in the stage of cancers detected in the USS group compared to the non-screening group.
Speculating why the finding of the disease in earlier stages did not translate into a reduction in overall deaths in this trial, Menon emphasized that it is an aggressive disease and that perhaps the treatments available then (10 years ago) they were unable to stop their progression.
Since the end of this trial 10 years ago, there have been significant improvements in the treatment of advanced ovarian cancer, noted Mahesh Parmar, PhD, MRC Clinical Trials Unit of the Institute of Clinical Trials and Methodology, UK, and lead author of the article.
“Our trial showed that screening was not effective in women who did not show any symptoms of ovarian cancer,” Parmar said.
However, he added that in “women with symptoms, early diagnosis, combined with this better treatment, can still make a difference in quality of life and potentially improve outcomes,” Parmar said in a statement. .
The researchers noted that this screening trial involved healthy women with no symptoms and no family history of ovarian cancer. They noted that among women at high risk for ovarian cancer, MMS performed every 3 to 4 months, along with risk-reducing surgery, has resulted in a significant reduction in the number of women diagnosed with advanced disease. .
It is not the first test of disappointment
UKCTOCS is not the first major screening trial to show that annual screening for ovarian cancer does not reduce mortality over a long-term follow-up period, said Lauren Hurwitz, PhD, National Cancer Institute, Rockville, Maryland, and colleagues of a accompanying editorial.
The first randomized controlled trial of ovarian cancer screening that was driven to assess cancer-specific mortality was the Prostate, Lung, Colorectal, and Ovarian Cancer (PLCO) Screening Assay. In this trial, more than 68,000 women were randomly assigned to undergo annual CA125 testing combined with transvaginal ultrasound or to receive routine care.
“After an average follow-up of 12.4 years, no detection was found to reduce ovarian cancer mortality,” observe Hurwitz and colleagues. In addition, almost 10% of the women in the intervention group received a false positive diagnosis. Subsequently, a considerable proportion of these patients were operated on.
Editorialists point out that in the current UK trial, the incidence of stage IV ovarian cancer may have been lower among women in the MMS group compared to women in the non-screening group.
However, somewhat paradoxically, “this difference was accompanied by a higher mortality rate for stage I cancers (14.8% in the MMS group vs. 9.4% in the non-screening group),” the editorialists note. .
One of the limitations of the study is that the researchers did not analyze mortality based on ovarian cancer histotypes, such as high-grade serous ovarian cancer, the most common and lethal histotype, they observe. the editorialists.
Editorialists agree with the study’s authors that alternative approaches to screening targeted at higher-risk women rather than women in the general population may be more effective in reducing ovarian cancer deaths and decreasing the likelihood of harm. by false positive screens.
“Detecting ovarian cancer remains difficult to prevent, but it is not a lost cause; there is simply more work to be done,” conclude Hurwitz and colleagues.
Researcher Jacobs hopes that a more effective screening test will eventually be found, although at the time a new screening test is evaluated in a large clinical trial, “we must reluctantly accept that the screening of the ovarian cancer population is more than a decade. “
The study was funded by the National Institute for Health Research, Cancer Research UK and Eve Appeal. Menon has shares awarded by University College London in Abcodia, has received grants from the Medical Research Council, (MRC) Cancer Research UK, the National Institute for Health Research (NIHR) and Eve Appeal. It also has patent for Lung cancer diagnosis. Parmar has received grants from MRC, Cancer Research UK, NIHR and Eve Appeal.