The majority of women diagnosed with ovarian cancer face a difficult journey of repeated treatments that include aggressive surgeries and multiple rounds of chemotherapy.
Despite our efforts to introduce effective new therapies, very few will find a long-term cure. This is because more than two-thirds of women don’t show signs of the disease until it’s reached an advanced stage, when long-term survival rates are around 20%. However, when detected early, we know more than 70% of ovarian cancer patients can be cured.
Which makes a recent announcement from physicians in the United Kingdom so exciting. A large clinical trial demonstrated the effectiveness and life-saving potential of a unique screening method for ovarian cancer. We are cautiously optimistic about the implications of this study for an ovarian cancer-screening program in the United States, but these results must be interpreted in the proper context of risk and reward.
The United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is distinctive in several ways: it’s the largest study to date (more than 200,000 post-menopausal women), has taken nearly 15 years to complete and uses a novel screening algorithm. Half of the women volunteering for the trial received routine care with no screening, one quarter underwent annual transvaginal ultrasound (TVUS), and one quarter had an annual blood test for a protein called CA-125, which was interpreted using a novel “Risk of Ovarian Cancer Algorithm” (ROCA). In the ROCA arm, if the algorithm detects a rapidly rising CA-125 from the previous year’s value, the woman will undergo TVUS. If the TVUS identifies an abnormal finding in the ovary, surgery may be performed.
U.S. practitioners for years have screened high-risk women using a blood test to detect CA-125. If a woman’s CA-125 is higher than a certain specified number, she’s flagged as “suspicious” for ovarian cancer. The United Kingdom’s UKCTOCS study, on the other hand, acknowledges that no two women are the same and therefore may have different baseline CA-125 levels. Unlike the U.S.’s “cutoff” method, the United Kingdom’s proposed “changes-over-time” method has the advantage of identifying a baseline CA-125 range for each individual woman, making it a uniquely personalized prevention strategy.
This individualized strategy produced some significant results. The UKCTOCS study revealed that women in its ROCA arm had about 15% fewer ovarian cancer deaths than those in the non-screening arm, similar to the relative benefit of mammography for women in their 40s. With these findings, many in the U.S. will advocate for its use here. But we know that screening can also cause harms such as unnecessary surgeries and associated complications. Before we consider implementing this in the U.S., we must clarify the benefits relative to harms and learn how best to communicate risk versus reward so women can make an informed decision about screening.
Demonstrating the number of lives saved from ovarian cancer is important, and the study showed that there was a 15% reduction in deaths in women who were screened. Another way to look at this is the number of women that must be screened to prevent one death. This study found that 641 women needed to be screened to prevent one ovarian cancer death. While the benefit for the one woman is huge, it’s not as clear for the remaining 640 women. However, this number is reasonable when considered in the context of other cancers. Mammograms, a routinely used screening practice, are known to save lives, but 1,500 women in their 40s must be screened to prevent one breast cancer death. For women in their 60s, that number falls to 400. The catch is that the estimate of 641 is only true for the women who were followed the longest, and it is imprecise: it could be as low as 375 and as high 1,934, therefore additional follow-up of more women is needed to figure out the true benefit.
It’s also important to assess the magnitude of harms, since all women entering a screening program may experience one of these harms. In the UKCTOCS trial, for every 10,000 women who entered the ROCA screening arm of the study, five fewer women died of ovarian cancer, but 18 had surgeries with negative findings.
Of special note, the UKCTOCS trial achieved its results by using a centralized, well-organized and consistent system that incorporated excellent quality control. Because the ROCA analysis is based on change in CA-125, the UKCTOCS centralized the CA-125 testing. Likewise, ultrasound was carefully quality-controlled and adherence to the follow-up algorithm was rigorously enforced. We need to caution physicians not to simply order a CA-125 test, but consider the best way to deliver a complex preventive cancer screening strategy to assure outcomes similar to those of the UKCTOCS. A smaller U.S. based multi-center ovarian cancer screening study with ROCA previously found that this type of screening strategy can be implemented with few false positives and a reasonable ratio of surgeries to cancers detected. Nevertheless, careful attention must be paid to the details of implementing this screening strategy, including strict adherence to protocols and quality assurance.
We may be at a turning point in the search for an effective strategy that decreases deaths by detecting ovarian cancer early. The advocacy community, enriched with passionate survivors and family members who have lost loved ones to ovarian cancer, have fiercely and consistently advocated for directing precious research funds to the discovery and validation of effective screening technologies. Taking time to consider the public health implications of this enormously large trial will help us in carving a rational path forward.
Karen Lu, M.D. Chair and Professor
Department of Gynecologic Oncology and Reproductive Medicine
MD Anderson Cancer Center
Mark Ebell, M.D. Professor of Epidemiology
College of Public Health
University of Georgia
NOTE: Dr. Ebell is a member of the United States Preventive Services Task Force (USPSTF). This article does not necessarily represent the views and policies of the USPSTF.