Long-Term Data Show No Survival Benefit Associated With Annual Screening in Women at Low Risk For Ovarian Cancer

Neither yearly transvaginal ultrasound nor multimodal screenings were associated with a significant reduction of deaths from tubal and ovarian cancer in women who were considered low risk for the disease, according to recently published data from a long-term study.

The results — which were published in The Lancet — demonstrate that screening the general population for tubal and ovarian cancer each year is not needed, according to the study authors.

“The case fatality for ovarian cancer is high meaning that a high proportion of patients diagnosed with it end up dying from the disease — mostly from advanced-stage disease,” Dr. Kristine Zanotti, program director of gynecologic oncology at University Hospitals Cleveland Medical Center, said in an interview with CURE®. “We have been looking for an effective screening method for a very long time.”

Because most women are diagnosed with late-stage disease and tend to have a poor prognosis, the study authors aimed to assess if yearly population screening could reduce disease-related deaths.

More than 200,000 postmenopausal women aged 50 years to 74 years were recruited from more than a dozen National Health Service trusts in the United Kingdom to participate in the trial. The women were then randomized to receive annual multimodal screening (50,625 individuals), annual transvaginal ultrasound screening (60,623 individuals) or no screening (101,314 individuals).

Zanotti, who was not an author on the study, noted that the participants were from the general population and considered low risk for developing the disease.

Measuring death due to tubal or ovarian cancer by June 2020 was the main goal of the study.

At a median follow-up of 16.3 years, 2,055 women were diagnosed with tubal or ovarian cancer. Of note, 522 women in the annual multimodal screening and 517 women in the annual transvaginal ultrasound screening were diagnosed with the disease.

Compared with the group who did not receive annual screening, there was a 47.2% increase in the incidence of stage 1 disease and 24.5% decrease in incidence of stage 4 disease among participants in the annual multimodal screening group. Moreover, the incidence of stage 1 or 2 disease was 39.2% higher in the multimodal group compared to the no screening group. Multimodal screening was also associated with a 10.2% lower incidence of stage 3 and 4 disease compared with the no screening group.

“I think that the screening programs can detect cancers at a higher rate; they just don't impact cancer mortality,” Zanotti said. “I think it's an important study in so far as at least it informs what's not effective, because I think many women request ultrasounds.”

Reducing the Risk

The lifetime risk of developing ovarian cancer in women who are not genetically susceptible to the disease, according to Zanotti, is approximately 2%. And although the data don’t show a clear benefit to annual screening in that population, Zanotti explained there are other ways women can lower their risk.

“When we understand risk factors, we can work towards modifying them,” she said.

One of the more effective methods for prevention is through preventive surgery, according to Zanotti. If a woman is no longer interested in having children or is older than 35, they can undergo a procedure to remove their tubes and ovaries to help prevent ovarian cancer. However, as Zanotti mentioned, this approach is not recommended for women who have no increased genetic risk of being diagnosed with the disease. The reason, she explained, is that there are trade-offs.

“You increase cardiovascular mortality risk by removing ovaries prematurely,” she said.

That is why Zanotti highlighted how that approach is usually only recommended in high-risk women. There are some ways to help women who are considered low risk prevent the incidence of ovarian cancer.

One way is to manipulate the number of lifetime ovulatory cycles a woman experiences, she explained. Essentially, consider an ovulation cycle a traumatic event. Each of those traumatic events can increase the odds of oxygen free radicals which are molecules that can negatively react with cells and cause DNA mutations over time. Oral birth control can affect the number of lifetime ovulations a woman may experience and has been shown to reduce the risk of endometrial and ovarian cancer.

Looking Ahead

There are several developments on the horizon that may help in the detection of ovarian cancer earlier on, however, as Zanotti explained, none are ready to be commercially distributed.

The goal, she noted, is to develop a test that is much more sensitive than the CA-125.

“There's hope that we can find more sensitive tests meaning fewer cells are necessary to detect the problem,” she said.

The hope, she continued, is to detect the cancer at an earlier point and have less risk of false negatives and false positives which can be seen with CA-125 testing.

Zanotti stressed that when people consider these results, they should remember this study evaluated women from the general population considered low risk for developing the disease.

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