Case May Be Building For Annual CA-125 Ovarian Cancer Screening

There are “tantalizing” trends toward reduced ovarian cancer deaths with annual cancer antigen 125 screening in a United Kingdom trial involving about 200,000, average-risk postmenopausal women, according to investigator Dr. Ian Jacobs of the University of New South Wales, Sydney.

From 2001-2005, a quarter of the women were randomized to annual cancer antigen 125 (CA-125) screening, with ultrasound follow-up and oncology referral as indicated; a quarter to annual transvaginal ultrasound screening and referral; and a half to no screening, as a control. Screening ended in Dec. 2011 (Lancet. 2016 Mar 5;387(10022):945-56).

Case May Be Building For Annual CA-125 Ovarian Cancer Screening

At a median follow-up of 11.1 years, there was a nonsignificant mortality reduction of 15% (95% confidence interval, –3 to 30; P = .10) with CA-125/ultrasound multimodal screening (MMS), and 11% reduction (95% CI, –7 to 27;P = .21) with ultrasound screening. A second analysis suggested a greater, though still nonsignificant, benefit after 7 years of screening, “which is typical of cancer screening trials,” Dr. Jacobs said at the annual meeting of the Society of Gynecologic Oncology.

When women who entered the trial with ovarian cancer were excluded, there was a statistically significant 20% (95% CI, –2 to 40) overall mortality reduction and 28% reduction (95% CI, –3 to 49) after year 7 in the MMS group, compared with controls (P = .021).

“The performance criteria are good” for MMS, “and the mortality data are somewhat persuasive, but not quite there yet. We need to continue follow-up for an additional 2-3 years. If the mortality reduction pans out, the health economics are probably similar to breast cancer screening. My hope is that by about 2020, we will be including ovarian cancer screening alongside breast and cervical cancer screening,” Dr. Jacobs said.

The study excluded women with previous ovarian malignancy and two or more first degree relatives with ovarian cancer. CA-125 was interpreted with the risk of ovarian cancer algorithm, which considers changes over time, with increases indicating potential problems.

Ovarian cancer was diagnosed in 338 (0.7%) women in the MMS arm, 314 (0.6%) women in the ultrasound arm; and 630 (0.6%) women in the control group. Mortality was lowest in the MMS group, with 148 (0.29%) succumbing to the disease, versus 154 (0.30%) in the ultrasound and 347 (0.34%) in the control arms.

MMS outperformed ultrasound screening on every measure, with a 25% positive predictive value, 448 false-positive operations with 345,990 screenings, one significant compilation per 23,066 screens, and compliance of 81%. MMS was also more likely to detect earlier stage disease.

With liquid biopsy and other potential screening tests coming online, “I’m pretty sure that in due course we will not be using just one test” for screening. “The dream scenario is that we end up with a panel of tests which could reduce mortality even more,” Dr. Jacobs said.

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