OVARIAN CANCER SCREENING

The largest trial of ovarian cancer screening — which compared annual screening with no annual screening in more than 200,000 women, who were followed for 14 years — has concluded that screening could reduce mortality from the disease by about 20%.

However, researchers from the United Kingdom Collaborative Trial of Ovarian Cancer (UKCTOCS) caution that longer follow-up is needed to determine the ultimate mortality reduction from screening and to determine whether screening in the general population is cost-effective.

"First-Ever Evidence"

"This is the first-ever evidence to suggest that screening for early detection of ovarian cancer may save lives," Ian Jacobs, MD, president and vice-chancellor of the University of New South Wales in Sydney, Australia, told Medscape Medical News.

"More follow-up is needed, but the results are encouraging and exciting and open up the possibility that many lives could be saved," said Dr Jacobs, who led the trial with Usha Menon, MD, from the Institute for Women's Health, University College London, United Kingdom.

"We have the first evidence that ovarian cancer screening can save lives, but we need further follow-up to confirm the findings," added Dr Menon.

"However, screening is not without harms, which include some women undergoing surgery to find they only have benign ovarian lesions or normal ovaries," she told Medscape Medical News.

"Our findings offer hope to the women and also to the research community that we can intervene to bring about change in the disease course. This, in turn, will provide fresh impetus for further research work in this area. In the medium term, we hope that we will be able to confirm, through follow-up of the trial participants for 2 to 3 years, the mortality reduction and determine the magnitude of the impact. This, along with our cost-effectiveness analysis and risks–benefits ratio, should allow a comprehensive assessment of whether ovarian cancer screening should be offered to women aged 50 and over in the general population," Dr Menon said

The long-term outcomes from this large screening trial were published online December 17 in the Lancet.

The researchers randomized more than 200,000 women from June 2001 to October 2005 to one of three group: 50,624 underwent annual multimodality screening, which consisted of a serum cancer antigen 125 (CA125) test interpreted with the risk of ovarian cancer algorithm (ROCA) plus ultrasound; 50,623 underwent annual transvaginal ultrasound screening alone; and 101,299 underwent no screening.

When screening ended in December 2011, the researchers had 345,570 multimodality screens and 327,775 ultrasound screens to evaluate.

The women from 13 centers in the United Kingdom were followed for 14 years.

All women were postmenopausal, 50 to 74 years of age, and had no history of bilateral oophorectomy, ovarian malignancy, increased risk for familial ovarian cancer, or nonovarian malignancy.

At a median follow-up of 11.1 years (interquartile range, 10.0 - 12.0), ovarian cancer had been diagnosed in 1282 (0.6%) women — 338 (0.7%) in the multimodality group, 314 (0.6%) in the ultrasound group, and 630 (0.6%) in the no-screening group.

Of the women who died of ovarian cancer, 148 (0.29%) were in the multimodality group, 154 (0.30%) were in the ultrasound group, and 347 (0.34%) were in the no-screening group.

Earlier Detection, Reduced Mortality with Screening

When the researchers analyzed the 14-year data, they found a reduction in the rate of death from ovarian cancer of 15% (95% confidence interval [CI], –3 to 30; P = .10) in the multimodality group and of 11% (95% CI, –7 to 27; P = .21) in the ultrasound group.

In the multimodality group, the reduction in mortality was 8% in the first 7 years and 23% in the subsequent 7 years.

In the ultrasound group, the reduction in mortality was 2% in the first 7 years and 21% in the subsequent 7 years.

When women who had undiagnosed ovarian cancer when they joined the trial were excluded from the analysis, the reduction in mortality rates related to screening improved.

Overall, there was an average reduction in mortality of 20% in favor of multimodality screening. The reduction in mortality was 8% in the first 7 years and 28% in the subsequent 7 years.

Cancer was detected at an early stage in more patients in the multimodality group than in the no-screening group (39% vs 26%; P < .0001).

"The primary analysis did not reach conventional statistical significance, so we cannot state definitively that screening saves lives, but it seems likely. Further follow-up is needed to be sure," said Dr Jacobs.

"The screening test involves a simple blood test, which can be done anywhere and sent to a lab," he said. This could have an effect on the more than 100,000 deaths from ovarian cancer each year around the world.

"Research now needs to accelerate to refine screening and confirm the benefit, so that, in due course, widespread national screening programs can be put in place," Dr Jacobs said.

Despite the encouraging results from UKCTOCS, detection of cancer was limited in both screened groups — at 59% in the multimodality group and 51% in the ultrasound group — write René H.M. Verheijen, MD, and Ronald P. Zweemer, MD, from the UMC Utrecht Cancer Center in the Netherlands, in an accompanying comment.

"If only 59% of ovarian cancer cases are detected by screening plus ultrasound, we will need to focus on why and how screening — as undertaken within UKCTOCS — still has a significant, but delayed, survival effect. Trying to unravel the mechanism behind this effect so that it can be improved should have a high priority," they write.

CA125 With the New Algorithm Boosts Detection

Ovarian cancer detection rates are better when the CA125 test is interpreted using the new algorithm, Dr Jacobs and his colleagues note.

ROCA is based on changes in serum CA125 levels over time, rather than on traditional fixed CA125 cutoff values, as previously reported by Medscape Medical News.

In an earlier study, the algorithm detected 87.1% of invasive epithelial ovarian or tubal cancers, compared with 41.3% with a fixed CA125 cutoff above 35 U/mL, 48.4% with a cutoff above 30 U/mL, and 66.5% with a cutoff above 22 U/mL (J Clin Oncol. 2015;33:2062-2071).

"On the basis of current evidence, the multimodal strategy using CA125 in the risk of ovarian cancer algorithm, followed by ultrasound as a secondary test where needed, seems to have the highest sensitivity or detection rate, the lowest false-positive rate, and the best evidence for a mortality reduction," Dr Jacobs reported.

"Some women will wish to access screening on an individual basis, having taken the view that, for them, the balance of benefit, harm, and cost makes it worthwhile. This decision will depend upon many factors, including a woman's level of risk of ovarian cancer, her views on health and screening, and the cost involved. Our advice is that women considering accessing screening should make a fully informed decision, having taken medical advice," he explained.

Longer Follow-up Needed

Experts agree that longer follow-up is needed to determine how effective annual screening will turn out to be.

"Although still at an early stage, the initial results from the UKCTOCS trial into screening for ovarian cancer are promising," Clare Mckenzie, MD, consultant gynecological oncologist and vice president of the Royal College of Obstetricians and Gynaecologists, said in a statement.

So far, results suggest that approximately 15 deaths could be prevented with CA125 screening for every 10,000 women screened, Dr Mckenzie noted. "However, for every woman with a positive screen who underwent surgery and was found to have ovarian cancer, two did not," she added.

"The early detection of ovarian cancer, and hence early treatment, has the potential to save lives. However, longer follow-up is needed to determine how effective the test is. Women who are worried about ovarian cancer should talk to their doctors, who can explain their risk of cancer and available tests," Dr Mckenzie said.