Is CA 125 or ultrasound screening appropriate for the general population?
Jacobs IJ, Menon U, Ryan A, et al. Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet. 2016;387(10022):945-956.
In the United States, the overall ovarian cancer 5-year survival rate is 46.2%, resulting in more than 14,000 deaths annually.2 The poor prognosis associated with this malignancy is largely attributable to the fact that almost 75% of women have stage III or stage IV disease at the time of diagnosis.2 Ovarian cancer is usually associated with vague, nonspecific symptoms as it progresses, which contributes to delayed diagnosis and increased mortality.
Multiple studies have examined pelvic ultrasonography and tumor markers, such as CA 125, as possible screening tools to increase early detection in asymptomatic women. However, neither modality alone or in combination has sufficient sensitivity or specificity to recommend it for use in the general population.3,4 Nevertheless, the search for an appropriate screening tool continues, and the UKCTOCS trial results have reinvigorated this discussion.5
Photo: © Steve Gschmeissner / Science Source
Colored scanning electron micrograph of a section through an ovary showing a dermoid ovarian tumor.
The UKCTOCS findings
The UKCTOCS was a multicenter, randomized controlled trial in the United Kingdom in which researchers allocated 202,638 women aged 50 to 74 years to 1 of 3 groups: annual multimodal screening (MMS) with serum CA 125 interpreted with the use of the risk of ovarian cancer algorithm, annual transvaginal ultrasound screening (USS), or no screening. The median follow-up was more than 11 years.
The investigators found that equivalent rates of ovarian cancer were diagnosed in each group: 0.7% in the MMS group, 0.6% in the USS group, and 0.6% in the no-screening group. Overall, there was no significant reduction in the mortality rate from ovarian cancer in either of the 2 screening groups compared with the no-screening group.5
An important subset discovery
However, in a prespecified subset analysis excluding "prevalent cases" (women with ovarian cancer thought to be present prior to randomization and subsequent screening), ovarian cancer mortality was significantly lower in the MMS group compared with the no-screening group (P = .021). Compared with no screening, MMS was associated with a 20% reduction in mortality rate from ovarian cancer over time, with the most pronounced effects occurring at years 7 to 14 of follow-up, suggesting the possible increased effectiveness of screening over time.5
Related article:
Can CA 125 screening reduce mortality from ovarian cancer?
Concordance with other screening trials
While impressive in study magnitude and scope, the UKCTOCS results did not demonstrate a significant mortality benefit associated with MMS or USS when compared with no screening. Although the screening complications were low (<1% in both screening groups), the authors did note a false-positive surgery rate of 14 per 10,000 screens for the MMS group and 50 per 10,000 screens for the USS group. Based on the performance of screening in this trial, 641 women would need to be screened annually using MMS for 14 years to prevent 1 ovarian cancer death.
Like the UKCTOCS, the ovarian cancer-screening arm of the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial in the United States was also unable to demonstrate a reduction in mortality rate with screening with CA 125 and transvaginal ultrasound. Importantly, more than one-third of women with a false-positive screen underwent surgery and 15% of them experienced a major complication.6 Based on these findings, the US Preventive Services Task Force grades screening for ovarian cancer as D, suggesting that the harms of screening may outweigh the benefits.7
WHAT THIS EVIDENCE MEANS FOR PRACTICE
While screening for ovarian cancer remains an important need, there is currently no evidence to suggest that serum tumor marker or ultrasound screening is appropriate in the general population. Studies using more specific screening tests or strategies targeted to higher-risk women are ongoing.
While screening for ovarian cancer remains an important need, there is currently no evidence to suggest that serum tumor marker or ultrasound screening is appropriate in the general population. Studies using more specific screening tests or strategies targeted to higher-risk women are ongoing.