USPSTF Recommends Against Ovarian Cancer Screening in Average- to Low-Risk Women

Women with no known high-risk hereditary syndrome should not be screened for ovarian cancer, according to a new review conducted by the US Preventive Services Task Force (USPSTF).

The USPSTF reviewed evidence from three “good-quality” studies on the benefits and harms of ovarian cancer screening in asymptomatic women with no known high risk for the disease. In particular, researchers on the task force evaluated ovarian cancer mortality, quality of life, false-positive rates, surgery and surgical complication rates, and psychological effects from screening.

The task force found adequate evidence that screening with transvaginal ultrasound or testing for the serum tumor marker cancer antigen-125 (CA-125), or both, does not reduce ovarian cancer mortality. In addition, they found that most women had false-positive results after screening, which led to unnecessary surgical interventions in a group of women who did not have cancer.

Ultimately, in a reiteration of its 2012 recommendation, they concluded with “at least moderate certainty” that the harms of screening outweighed the benefits.

“Given the lack of mortality benefit of screening, and the moderate to substantial harms that could result from false-positive screening test results and subsequent surgery, the USPSTF concludes with moderate certainty that the harms of screening for ovarian cancer outweigh the benefit, and the net balance of the benefit and harms of screening is negative,” the task force wrote.

Review Evidence

In the largest and most recent trial, the randomized UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) trial included 202,638 postmenopausal women, aged 50 to 74 years, not known to be at high risk for ovarian cancer, who underwent CA-125 screening or transvaginal ultrasound.

After a median follow-up of 11.1 years, ovarian cancer mortality was not significantly different among both screening groups, and compared with a control group who received no screening. In addition, there was no significant difference in mortality risk in the transvaginal ultrasound [hazard ratio (HR) = 0.91; 95% CI, 0.76-1.09] compared with the CA-125 (HR = 0.89; 95% CI, 0.74-1.08) groups.

The pilot trial for the UKCTOCS trial included 21,955 women to evaluate the use of a single cutoff value for CA-125 testing. Again the researchers found no difference in ovarian cancer mortality.

In the US-based PLCO trial, 68,557 women were randomized to receive either annual screening — using both CA-125 and transvaginal ultrasound – or usual care.

After a median follow-up of 12.4 years, the researchers found no difference in ovarian cancer mortality among groups. Recent analyses of the trial, which added six more years of data, also did not find evidence to support long-term benefits from screening.

Based on all three studies, the false-positive rates were 11.9% among women screened with transvaginal ultrasound and 9% in those screened with CA-125.

A fourth study — the Quality of Life, Education and Screening Trial (QUEST) – determined quality of life and the psychological harms of screening among 549 women.

Although researchers found no statistically significant difference in cancer worry between screening groups, women with abnormal test results were more likely to report cancer worry at 2 years of follow-up (odds ratio = 2.8; 95% CI, 1.1-7.2) than women who did not have abnormal results.

“This recommendation statement is consistent with the 2012 USPSTF recommendation,” the task force wrote. “Since 2012, the large UKCTOCS trial was published, and much like the PLCO trial, it did not find that screening for ovarian cancer reduces ovarian cancer mortality in asymptomatic women not known to be at high risk for ovarian cancer.”

Improved Strategies

In conjunction with the USPSTF’s recommendation, Karen H. Lu, MD, added that early detection strategies are possible.

“Important lessons learned over the last 2 decades should help to develop improved strategies for early detection of ovarian cancer,” she wrote in an accompanying editorial.

First, Lu suggests a two-stage strategy — including a first-stage, inexpensive test followed by an imaging test – could be effective in in early detection. She also highlighted the fact that samples used for the discovery of new biomarkers must be “prediagnostic.”

Lastly, Lu acknowledged that validation of candidate biomarkers is essential, and previous studies — such as UKCTOCS and PLCO – could serve as validation of these new candidates.

“While efforts continue to identify effective strategies for early detection, to truly reduce the morbidity and mortality of ovarian cancer, a complementary prevention strategy also will be needed,” said Lu. “Broadening the strategy to include accurate risk models and genetic testing, novel prevention options, and effective early detection may help reduce the incidence and high mortality associated with ovarian cancer.”