Expert Commentary

Can CA 125 screening reduce mortality from ovarian cancer?

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Yes, according to promising, but preliminary, findings from a large United Kingdom (UK) trial that demonstrated an overall average mortality reduction of 20% with use of annual multimodal screening with serum CA 125, interpreted by applying a proprietary cancer risk algorithm.

Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomized controlled trial [published online ahead of print December 17, 2015]. Lancet. doi:10.1016/S0140-6736(15)01224-6.



To date, screening has not been found effective in reducing mortality from ovarian cancer. Collaborative trial investigators in the United Kingdom studied postmenopausal women in the general population to assess whether early detection by screening could decrease ovarian cancer mortality.

Details of the study
During 2001 to 2005, more than 200,000 UK postmenopausal women aged 50 to 74 years (mean age at baseline, 60.6 years) were randomly assigned to no screening, annual transvaginal ultrasound screening (TVUS), or annual multimodal screening (MMS) with serum CA 125 using the Risk of Ovarian Cancer Algorithm (ROCA), which takes into account changes in CA 125 levels over time. When ROCA scores indicated normal risk for ovarian cancer, women were advised to undergo repeat CA 125 assessment in 1 year. Women with intermediate risk were advised to repeat CA 125 assessment in 3 months, while high-risk women were advised to undergo TVUS.

With a median of 11.1 years of follow-up, ovarian cancer (including fallopian tube malignancies) was diagnosed in 1,282 participants (0.6%), with fatal outcomes among the 3 groups as follows: 0.34% in the no-screening group, 0.30% in the TVUS group, and 0.29% in the MMS group. Based on the results of a planned secondary analysis that excluded prevalent cases of ovarian cancer, annual MMS was associated with an overall average mortality reduction of 20% compared with no screening (P = .021). When the mortality reduction was broken down by years of annual screening, 0 to 7 years was associated with an 8% mortality reduction over no screening, and this jumped to 28% for 7 to 14 annual MMS screening years.

The overall average mortality reduction with TVUS compared with no screening was smaller than with MMS. With MMS, the number needed to screen to prevent 1 death from ovarian cancer was 641.

Assessing unnecessary treatment
False-positive screens that resulted in surgical intervention with findings of benign adnexal pathology or normal adnexa occurred in 14 and 50 per 10,000 screens in the MMS and TVUS groups, respectively. For each ovarian cancer detected in the MMS and TVUS groups, an additional 2 and 10 women, respectively, underwent surgery based on false-positive results.

This massive trial’s findings provide optimism that screening for ovarian cancer can indeed reduce mortality from this uncommon but too-often lethal disease. There are unanswered questions, however, which include the cost-effectiveness of MMS screening and how well this strategy can be implemented outside of a highly centralized and controlled clinical trial. While encouraging, these trial results should be viewed as preliminary until additional efficacy and cost-effectiveness data—and guidance from professional organizations—are available.

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