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Long-term follow-up of a huge randomized trial found that ovarian cancer screening with transvaginal ultrasound alone or in combination with CA125 blood testing did not reduce mortality from the disease compared with no screening, though use of CA125 detected cancers at an earlier stage.

At a median follow-up of 16.3 years, incidence of ovarian or tubal cancer was the same in each of the three groups (1.0%), as was the incidence of ovarian and tubal cancer deaths (0.6%), according to researchers led by Usha Menon, MD, of University College London.

"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," Menon said in a .

Despite these identical outcomes, a multimodal screening (MMS) approach -- CA125 blood test plus transvaginal ultrasound screening (USS) -- was able to detect earlier-stage disease, with a 47.2% increase in the incidence of women detected with stage I disease and a 24.5% decrease in stage IV disease compared with the no-screening group, they reported in .

"UKCTOCS [] is the first trial to show that screening can definitely detect ovarian cancer earlier. However, this very large, rigorous trial clearly shows 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," she said.

In the U.K. study, 202,638 postmenopausal women ages 50 to 74 were enrolled from 2001 to 2005. Participants were randomized to undergo annual MMS, USS alone, or no screening, in a 1:1:2 ratio, with screening ending in 2011. The primary outcome was death due to ovarian or tubal cancer.

Menon and colleagues noted that the reductions in earlier-stage disease incidence were countered by a higher case fatality rate for stage I cancers among the MMS group compared with the no-screening group (14.8% vs 9.4%). Overall, the incidence of stage I/II disease was 39.2% higher in the MMS group than the no-screening group, but only a 10.2% decrease in overall incidence of stage III/IV disease was observed.

The trial's , published in 2015 with a median follow-up of 11.1 years, showed no significant mortality reduction in either screening group, but did find that the difference in mortality appeared to widen over time. The researchers said they therefore hoped that a delayed mortality benefit would appear with additional follow-up.

They explained that previous studies have shown that a large reduction in late-stage incidence is a prerequisite for reducing cancer mortality, and suggested that in the case of ovarian and tubal cancer, the high mortality associated with stage III and IV disease, combined with the large number of women clinically detected with stage III disease, "requires a substantial reduction in the incidence of both stages before a mortality reduction is possible."

"We need a screening strategy than can detect ovarian and tubal cancer in symptomatic women even earlier in its course and in a larger proportion of women than the tests used in the trial," Menon and co-authors said. "Meanwhile, our results emphasize the importance of having ovarian and tubal cancer mortality as the primary outcome in screening trials."

In a , Lauren M. Hurwitz, MHS, PhD, of the National Cancer Institute in Rockville, Maryland, and colleagues said it is "probable" the results will mean the end of general population ovarian cancer screening with CA125 or USS either alone or in combination.

Hurwitz and co-authors said there is still a potential for additional protein biomarkers to be used alone or in combination with CA125, "but these markers as screening tools will need to be further developed, validated, and ultimately tested in randomized controlled trials."

Advances in imaging, as well as targeting women at higher risk of ovarian cancer, could be more effective in reducing ovarian cancer deaths, the editorialists noted. "Consequently, screening for ovarian cancer remains elusive but is not a lost cause; there is simply much more work to be done."

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