No Benefit to CA-125 Ovarian Cancer Screening for General Population

The largest-ever study evaluating ovarian cancer screening for the general population showed only a modest reduction in the risk of death after more than a decade of follow-up. The use of changes in CA125 markers over time or transvaginal ultrasound, failed to achieve statistical significance versus no screening in primary analysis, according to a study published Dec. 17, 2015 in The Lancet, but the authors were encouraged by the screening methods' greater mortality reductions with longer follow-up periods.

Experts say the long-awaited study results don't justify screenings for the general population, but acknowledge more research is needed both in assessing these screening modalities, as well as emerging markers.

This trial, the UK Collaborative Trial of Ovarian Cancer Screening, included postmenopausal women (aged 50 to 74 years) screened at 13 National Health Service Trust centers in the United Kingdom. Women with increased risk of familial ovarian cancer were excluded from the study. Women were randomized to annual multimodal screening (MMS) with serum CA125 interpreted with use of the risk of ovarian cancer algorithm (n= 50,624), annual transvaginal ultrasound screening (USS; n= 50,623), or no screening (n= 101,299). The risk of ovarian cancer algorithm (ROCA) categorized women in the MMS group as normal (annual screening); intermediate risk (repeat CA125 concentration testing in 3 months); and elevated (repeat CA125 concentration testing and transvaginal ultrasound as a second-line test in 6 weeks).

The researchers found that at a median follow-up of 11.1 years ovarian cancer was diagnosed in 1,282 women overall (0.6 percent) with 338 (0.7 percent) in the MMS group, 314 (0.6 percent) in the USS group, and 630 (0.6 percent) in the no screening group. Death occurred in 148 of the diagnosed women in the MMS group (0.29 percent), 154 in the USS group (0.30 percent), and 347 in the no screening group (0.34 percent). Screening yielded a mortality reduction over years 0 to 14 of 15 percent with MMS and 11 percent with USS—both statistically insignificant.

However, upon further prespecified analysis, with exclusion of the prevalent cases of ovarian group in the MMS group, the mortality reduction became significant. The authors say the long-term effect of an MMS screening program is about a 28 percent mortality reduction after seven years of screening. Findings from this trial suggest that for 641 women screened annually using the multimodal strategy for 14 years, one ovarian cancer death is prevented.

"This late effect was predictable in view of the unavoidable time interval from randomization to diagnosis and then death. For participants who died in the no screening group the median interval from randomization to death was more than 8 years," write the authors led by Ian Jacobs, M.D., who co-invented ROCA. "The mortality hazard rate in the no screening group seems to increase, whereas in the two screened groups, it levels off. … This finding suggests that the difference in mortality between no screening and screening groups will increase with time and further follow-up."

Takeaway: Ovarian cancer screening using a CA-125 algorithm-dependent strategy is not yet justifiable for the general population of women.