Early Detection of Ovarian Cancer Looks Feasible, But More Data Needed

Roxanne Nelson

March 20, 2009

March 20, 2009 — Both the cancer antigen 125 (CA125) blood test and transvaginal ultrasound might be capable of detecting early-stage ovarian cancers. The results of the largest randomized controlled trial of ovarian cancer screening to date, conducted in the United Kingdom, suggest that transvaginal ultrasound or a multimodal strategy that includes CA125 testing and ultrasound are effective in detecting early-stage disease.

On the initial screening, almost half (48.3%) of the cancers detected were either stage I or II, but specificity was higher in the multimodal group than in the group that women underwent ultrasound only. This resulted in fewer repeat tests and almost 9 times fewer surgical procedures per cancer detected.

The stage distribution of the screen-detected primary invasive cancers was similar in both groups, the authors report in a study published online March 10 in the Lancet Oncology, but a larger number of borderline epithelial ovarian neoplasms were detected in the ultrasound group than in the multimodal group.

No Data Yet on Mortality

Despite the encouraging results, the authors are not making any screening recommendations; screening will not be completed until December 31, 2011. Currently, ovarian cancer screening is only recommended for those at very high risk for the disease, and this is true for the United Kingdom and the United States.

"Screening should only be offered to the very-high-risk group until the evidence for benefit of broader population screening is available," explained senior author Ian Jacobs, MD, director of the National Institute for Health Research, Comprehensive Biomedical Research Centre, at UCLH/UCL, in London, United Kingdom.

The offer of screening on a population basis needs . . . evidence of efficacy.

The offer of "screening on a population basis needs . . . evidence of efficacy from our randomized controlled trial and others that are ongoing," Dr. Jacobs told Medscape Oncology. "If the evidence indicates an overall benefit, then in due course population screening, probably confined to postmenopausal women or women over 50 years and to high-risk women with a family history, may be implemented, alongside breast and cervical cancer screening."

The effect of screening on mortality has not been determined. This is the primary outcome measure for the study and the data are not available yet. Initial follow-up will continue until the end of December 2014, so the final results will not be available until then, explained Dr. Jacobs.

"Our trial is designed to establish how many lives can be saved, the psychological impact of screening, the morbidity due to false positives, and the financial cost," he said. "The Lancet Oncology report is an interim report of the first round of screening and, although the results are encouraging in that most cancers were detected and there is some evidence of a stage shift, there is a long way to go before we will be able to establish whether or not we are detecting cancer early enough to save lives."

Better Specificity With Multimodal Approach

The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) was designed to assess the effect of screening on ovarian-cancer-related mortality, and consisted 202,638 postmenopausal women aged 50 to 74 years who were randomized to 1 of 3 groups: annual CA125 screening (interpreted using a risk-of-ovarian-cancer algorithm) with transvaginal ultrasound scan as a second-line test (multimodal group; n = 50,640); annual screening with transvaginal ultrasound alone (ultrasound group; n = 50,639); or to a control group with no screening (n = 101,359). Women with repeat abnormal screens underwent clinical evaluation and surgery.

Repeat screening was required for 8.7% of women in the multimodal group and for 12.0% in the ultrasound group. Of the repeat-screening cohort, 0.3% of women in the multimodal group required clinical evaluation, as did 3.9% of women in the ultrasound group

In the multimodal group, 97 women (0.2%) underwent surgery, whereas in the ultrasound group, 845 women (1.8%) underwent surgery. There were 42 primary ovarian and tubal cancers detected in multimodal group and 45 in the ultrasound group; 28 of these were borderline tumors (8 multimodal and 20 ultrasound).

The researchers also observed that 28 of the invasive cancers (16 multimodal and 12 ultrasound) were stage I or II, and there was no difference in stage distribution between the 2 cohorts (P = .396). An additional 13 primary ovarian cancers were diagnosed clinically during the year following the screening.

Sensitivity, Specificity, and Positive Predictive Value (PPV) for All Primary Ovarian and Tubal Cancers

Screening Group Sensitivity Specificity PPV
Multimodal (%) 89·4 99.8 43.3
Ultrasound (%) 84.9 98.2 5.3

A significant difference was noted in specificity (< .0001) but not in sensitivity between the 2 screening groups for primary ovarian and tubal cancers and for primary epithelial invasive ovarian and tubal cancers, write the authors.

"At this time, it appears that multimodal screening has advantages over ultrasound alone in reducing some of the high costs and harms of ovarian cancer screening that have been identified over the past 2 decades," said Robert Smith, PhD, director of cancer screening at the American Cancer Society, who was approached for independent comment. "And while these early findings are promising, a higher rate of early-stage disease is not sufficient to conclude that ovarian cancer screening is effective and should be recommended to postmenopausal women."

This important trial will continue screening women.

"This important trial will continue screening women and eventually compare mortality rates in the control group with those in the 2 screening regimens," he said. "At that time, we'll have a better idea if screening for ovarian cancer screening can be endorsed.

The study received funding from the Medical Research Council, Cancer Research UK, and the Department of Health, UK. Additional support was received from the Eve Appeal, Special Trustees of Bart's and the London, and Special Trustees of University College London Hospital. Dr. Jacobs has consultancy arrangements with Vermillion and Becton Dickinson, both of which have an interest in tumor markers and ovarian cancer. Coauthor Steven J. Skates, PhD, from Harvard Medical School, in Boston, Massachusetts, has received research support from Fujirebio Diagnostics, but not in relation to this trial. Both are coinventors of the risk-of-ovarian-cancer algorithm, patent number 5800347. None of the other authors have disclosed any relevant financial relationships.

Lancet Oncol. Published online before print March 10, 2009. Abstract

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