Elsevier

The Lancet

Volume 353, Issue 9160, 10 April 1999, Pages 1207-1210
The Lancet

Articles
Screening for ovarian cancer: a pilot randomised controlled trial

https://doi.org/10.1016/S0140-6736(98)10261-1Get rights and content

Summary

Background

The value of screening for ovarian cancer is uncertain. We did a pilot randomised trial to assess multimodal screening with sequential CA 125 antigen and ultrasonography.

Methods

Postmenopausal women aged 45 years or older were randomised to a control group (n=10977) or screened group (n=10958). Women randomised to screening were offered three annual screens that involved measurement of serum CA 125, pelvic ultrasonography if CA 125 was 30 U/mL or more, and referral for gynaecological opinion if ovarian volume was 8·2 mL or more on ultrasonography. All women were followed up to see whether they developed invasive epithelial cancers of the ovary or fallopian tube (index cancers).

Findings

Of 468 women in the screened group with a raised CA 125, 29 were referred for a gynaecological opinion; screening detected an index cancer in six and 23 had falsepositive screening results. The positive predictive value was 2·7%. During 7-year follow-up, ten further women with index cancers were identified in the screened group and 20 in the control group. Median survival of women with index cancers in the screened group was 72·2 months and in the control group was 41·2 months (p=·112). The number of deaths from an index cancer did not differ significantly between the control and screened groups (18 of 10977 vs nine of 10958, relative risk 2·2 [95% CI ·78–5·23]).

Interpretation

These results show that a multimodal approach to ovarian cancer screening in a randomised trial is feasible and justify a larger randomised trial to see whether screening affects mortality.

Introduction

The 5-year survival rate after diagnosis of ovarian cancer is about 30%, although survival rates of 85% or more are seen with stage I disease.1 After the identification of the CA 125 antigen2, 3 and the use of ultrasonography in ovarian imaging4 several prospective studies of screening were done. These studies showed that a substantial proportion of ovarian cancers can be detected before symptoms arise by measurement of CA 125,5, 6, 7, 8, 9, 10 by real-time ultrasonography,11, 12, 13, 14, 15, 16 and by colour-flow doppler.13, 17, 18, 19 The studies also revealed limitations in specificity and positive predictive value, and they were not designed to assess the impact of screening on mortality.20

In previous studies, we addressed the issues of specificity and positive predictive value by a screening strategy that involved a sequential approach with CA 125 as a primary test and pelvic ultrasonography as a secondary test. The findings in the first 1010 women screened suggested that high specificity and positive predictive value could be achieved in postmenopausal women with this strategy.5, 21 Subsequently, a larger prevalence screen of 22000 postmenopausal women confirmed the specificity and positive predictive value and showed a sensitivity of 79% at 1-year follow-up.6 The effect of screening on mortality from ovarian cancer remained unclear. No randomised controlled trials of ovarian-cancer screening have yet been reported and the potential of screening to alter the natural history of ovarian cancer is uncertain. We did a randomised controlled trials to assess the feasibility of ovarian cancer screening and provide information about the impact of annual screening on a previously screened population.

Section snippets

Participants

Eligibility for the study was limited to women resident in the UK who were aged 45 years or older and who were postmenopausal (1 year or more amenorrhoea). Exclusion criteria were a history of bilateral oophorectomy or ovarian cancer. Invitations to participate were sent to 22000 women who had participated in our previous study of screening for ovarian cancer.6 We told women about the uncertain impact of screening for ovarian cancer and the need for a randomised controlled trial. They were told

Results

65 women were excluded before randomisation because of documented bilateral oopherectomy (30); subsequent diagnosis of ovarian cancer (19); death (nine); or withdrawal (seven). Of the 10958 women in the screening group 7743 (7·7%) completed all three screens and 9364 (85·2%) completed at least one screen (figure 1). In the screening group, 468 women underwent 781 ultrasound scans because of raised CA 125, and 29 women underwent surgical investigation (table 1). Of these 29 women, six had an

Discussion

This trial has provided useful information about the feasibility of a randomised trial of ovarian cancer screening by sequential CA 125 and ultrasonography, which will help to guide the design of future trials. Compliance with follow-up suggest that the method was acceptable to women in the control and screen groups. We found the screening strategy to be feasible and the high rate of women with at least one screen (86%) suggests that participants found the approach acceptable. There was only a

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