Screening for ovarian cancer

COMMENTARY

CORRESPONDENCE

Screening for ovarian cancer Sir—I would be grateful if Ian Jacobs and colleagues (April 10, p 1207)1 could clarify the following issues about their report on screening for ovarian cancer. It seems that the screened population they refer to had already been screened twice before by means of measurement of serum CA 125 antigen and ultrasonography. 2 4 1 women with abnormal screening underwent operations, and 11 ovarian cancers were discovered. There were altogether 19 ovarian cancers in the group of 22 000 women tested and those women were removed from the cohort. The rest of the women were then randomised to screening or no screening to make the sample of the new study. Do the authors think that this study is representative of the general population? There were 340 women with raised CA 125 among the 22 000 women tested,2 which amounts to 1·54% of the population with abnormal values. Among 8723 patients tested with CA 125,1 254 had abnormal values (2·9%). Any possible explanation for an almost two-fold increase in the second group, which—as mentioned before—had already been screened twice? Which are the true numbers: the numbers in the text—with 9364 women with one screen and 7743 women with three screens—or the numbers in figure 1 and table 1—with 8732 with one screen and 8455 with three screens? In view of what is said in the summary about survival and mortality, I find it difficult to interpret the following passage in the Discussion: “survival differed significantly between women with index cancer in the screened and control groups, but this finding is not definitive evidence for lack of benefit from screening for ovarian cancer.” The prevalence of ovarian cancer has been estimated at 50 per 100 000 women.3 There is evidence to suggest that the use of oral contraceptives may decrease the relative risk of ovarian cancer in ever users by 40%.4 This point should be taken into account

THE LANCET • Vol 354 • August 7, 1999

before resources are committed to a larger study of the feasibility of screening programmes for ovarian cancer. Nikolai Manassiev 58 Ollerton Road, Yardley, Birmingham, B26 1PN, UK 1

Jacobs I, Skates S, MacDonald N, et al. Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 1999; 353: 1207–10. 2 Jacobs I, Davies A, Bridges J, et al. Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography. BMJ 1993; 306: 1030–34. 3 NIH Consensus Development Panel on Ovarian Cancer. Ovarian cancer: screening, treatment and follow-up. JAMA 1995; 273: 491–97. 4 Beral V, Hermon C, Kay C, et al. Mortality associated with oral contraceptive use: 25 year follow-up of cohort of 46 000 women from Royal College of General Practitioners’ oral contraception study. BMJ 1999; 318: 96–100.

Sir—In the light of Woodman’s report 1 about Ian Jacobs and colleagues’ study,2 we disagree with the optimistic conclusion reached by the investigators and believe a more cautious interpretation is justified. Jacobs and colleagues specifically report only the positive-predictive value of the strategy (20·7%), and compare this with other current methods of screening for ovarian cancer. This single factor is sufficient to make decisions about a screening test. On the basis of the figures for women who completed at least one screen (9364), the strategy has a sensitivity of 37·5%, specificity of 99·75%, and negative-predictive value of 99·89%. A screening test should have high sensitivity (especially for rare disease) and be followed by a diagnostic test with high sensitivity and specificity, leading to a strategy with high sensitivity and high positivepredictive value. The reported strategy has low sensitivity and low positivepredictive value. Since the subsequent investigation of any positive test involves major abdominal surgery, a high positive-predictive value is particularly important. Although data on certain risk factors are presented for each group, family

history of ovarian cancer is not reported. Given the voluntary nature of recruitment to this study, we do not know if the population studied were representative, or if in fact they included a disproportionate number of women with increased genetic risk of ovarian cancer. This bias could potentially affect the uptake of the test and its detection rate. Jacob and colleagues conclude that this pilot study justifies a much larger trial to show an effect on mortality, and to assess economic and psychosocial factors. It is a pity that this study of 22 000 women d i d n o t include these additional assessments. It would be interesting to know the psychological and physical impact on the 23 women who underwent major abdominal surgery for a false-positive screen, and the effect on the ten women reassured by the test who subsequently developed ovarian cancer.3 We believe that this study shows the lack of an adequate population screening tool for ovarian cancer, and highlights the difficulties of searching for screening tools for r a r e diseases. Perhaps a more appropriate strategy will be shown from studies currently in progress of targeted screening for women at increased genetic risk of ovarian cancer, or from the development of more sensitive biological markers of the disease? *Jon Emery, John Yaphe, Patricia Priest, David Whiteman Division of Public Health and Primary Health Care, Institute of Health Sciences, Headington, Oxford OX3 7LF, UK 1

Woodman R. Ovarian cancer screening may increase survival. BMJ 1999; 318: 1027. 2 Jacobs I, Skates S, MacDonald N, et al. Screening for ovarian cancer: a pilot randomised controlled trial. Lancet 1999; 353: 1207–10. 3 Stewart-Brown S, Farmer A. Screening could seriously damage your health. BMJ 1997; 314: 533–34.

Sir—Ian Jacobs and colleagues 1 report the results of a population-based randomised trial of screening for ovarian cancer in postmenopausal women. The women were first screened by measurement of serum CA 125, and those who had had a

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