Ann Prys Davies

Screening for ovarian cancer: a pilot randomised controlled trial

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=10,977) or screened group (n=10,958). 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 8.8 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 false-positive screening results. The positive predictive value was 20.7%. 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 72.9 months and in the control group was 41.8 months (p=0.0112). The number of deaths from an index cancer did not differ significantly between the control and screened groups (18 of 10,977 vs nine of 10,958, relative risk 2.0 [95% CI 0.78-5.13]). 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.

Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography.

OBJECTIVE--To assess the performance of the sequential combination of serum CA 125 measurement and ultrasonography in screening for ovarian cancer. DESIGN--The serum CA 125 concentration of each subject was determined and those with a concentration > or = 30 U/ml were recalled for abdominal ultrasonography. If ultrasonography gave abnormal results surgical investigation was arranged. Volunteers were followed up by annual postal questionnaire. SETTING--General practice, occupational health departments, ovarian cancer screening clinic. SUBJECTS--22,000 women volunteers who were postmenopausal and aged over 45 years. MAIN OUTCOME MEASURES--Apparent sensitivity, specificity, positive predictive value, years of cancer detected. RESULTS--41 women had a positive screening result and were investigated surgically. 11 had ovarian cancer (true positive result) and 30 had other disorders or no abnormality (false positive result). Of the 21,959 volunteers with a negative screening result, eight subsequently presented clinically with ovarian cancer (false negative result) and 21,951 had not developed ovarian cancer during follow up (apparent true negative result). The screening protocol achieved a specificity of 99.9%, a positive predictive value of 26.8%, and an apparent sensitivity of 78.6% and 57.9% at one year and two year follow up respectively. The estimated number of years of cancer detected by the prevalence screen was 1.4 years. CONCLUSIONS--This screening protocol is highly specific for ovarian cancer and can detect a substantial proportion of cases at a preclinical stage. Further investigation is required to determine the effect of the screening protocol on the ratio of early to late stage disease detected and on mortality from ovarian cancer.

Risk of diagnosis of ovarian cancer after raised serum CA 125 concentration: a prospective cohort study

Abstract Objective: To determine the risk of invasive epithelial ovarian cancer and fallopian tube cancer associated with a raised concentration of the tumour marker CA 125 in asymptomatic postmenopausal women. Design: Serum CA 125 concentration was measured annually in study participants for one to four years. Participants with a concentration >/=30 U/ml were recalled for abdominal ultrasonography. Follow up was by annual postal questionnaire. Setting: General practice, occupational health departments, ovarian cancer screening unit in a teaching hospital. Subjects: 22 000 volunteers, all postmenopausal women >/=45 years of age; recruited between 1 June 1986 and 1 May 1990. Intervention: Surgical investigation if the ultrasound examination was abnormal. Main outcome measures: Cumulative and relative risk of developing an index cancer (invasive epithelial cancer of the ovary or fallopian tube) after a specified CA 125 result. Results: 49 index cancers developed in the study population during a mean follow up of 6.76 years. The overall cumulative risk of developing an index cancer was 0.0022 for the entire study population and was lower for women with a serum CA 125 concentration <30 U/ml (cumulative risk 0.0012) but was appreciably increased for women with a concentration >/=30 U/ml (0.030) and >100 U/ml (0.149). Compared with the entire study population the relative risk of developing an index cancer within one year and five years was increased 35.9-fold (95% confidence interval 18.3 to 70.4) and 14.3-fold (8.5 to 24.3) respectively after a serum CA 125 concentration >/=30 U/ml and 204.8-fold (79.0 to 530.7) and 74.5-fold (31.1 to 178.3) respectively after a concentration >/=100 U/ml. Conclusion: CA 125 is a powerful index of risk of ovarian and fallopian tube cancer in asymptomatic postmenopausal women. Key messages This study shows that raised serum CA 125 concentration is a powerful index of risk of ovarian cancer in asymptomatic postmenopausal women The risk in the year after a serum CA 125 concentration >/=100 U/ml is similar to the lifetime risk to women in high risk families The importance of a raised serum CA 125 concentration in relation to risk of other cancers is not yet known The role of CA 125 as a component of a screening strategy for ovarian cancer is under investigation, but the impact on mortality is not known

Raised serum CA 125 preceding the diagnosis of carcinoma of the fallopian tube: two case reports

A 52-year-old woman volunteered to participate in a multi-modal screening programme for ovarian cancer in asymptomatic postmenopausal women at The London Hospital (Jacobs et al. 1988). She had had one child but was now postmenopausal. Serum CA 125 was determined using the Abbot Laboratory CA 125 radioimmunoassay. An abnormal level was defined as >30 U/ml (Bast et af. 1983). Her initial CA 125 level in venous blood was elevated at 43.7 U/ml. Consequently real-time pelvic ultrasonography (transabdominal) was performed in accordance with the study protocol. This showed both ovaries to be of normal volume and morphology. No abnormality was noted. She was followed up by 3 monthly serum CA 125 measurements, again in accordance with the study protocol. The serum level remained mildly elevated at 32.2, 35 and 38 U/ml at 3, 6 and 9 months respectively. At 11 months after her initial CA 125 measurement she developed lower abdominal discomfort. A repeat ultrasound scan identified a 7 cm solid left-sided pelvic mass. At laparotomy she was found to have a carcinoma of the left fallopian tube and a hysterectomy, bilateral salpingo-oophorectomy and omentectomy was performed. Histological examination confirmed a poorly differentiated papillary adenocarcinoma of the left fallopian tube (Stage I).

Are all Districts Equally Ready for “Shared Care” of Drug Misusers?

All GPs in three neighbouring districts were sent a questionnaire concerning attitudes towards drug raisusers and their treatment beliefs. 79 % (270) returned completed questionnaires. Two of the districts showed similar attitude scores towards opiate users and their treatment but the third district contained significantly more GPs with negative attitudes. Social deprivation scores did not appear important. GPs who had experience of prescribing for drug users and were of younger age were more likely to have positive opinions. This study demonstrates an apparent positive shift in opinion and attitude of GPs and provides indications for purchasers wishing to develop “shared care” of drug misusers. However they must first assess local conditions before they can set targets and allocate resources.

Is an elevated maternal serum CA125 in early pregnancy an indicator of abnormal fetal karyotype? A retrospective analysis

SummaryIt has been suggested that early first trimester maternal serum CA125 levels may be raised in pregnancies complicated by fetal chromosome anomalies. A retrospective study of maternal serum CA125 levels at 6–8 weeks in 8 pregnancies with a variety of fetal karyotypic abnormalities failed to confirm this finding.

The use or uselessness of annual public health reports: Response from author of report

Editor—I scarcely recognise my paper Reporting the Public Health from reading Scally’s editorial.1,2 I do not argue for centralisation of funding, merely that the budget for the production and dissemination of annual reports should be administered, and thereby ring fenced as a protected public health function, by the minister for public health. This could elevate the exercise in those authorities where it has often been done on the cheap with little attention to impact. It would also prevent any further merging of annual public health reports with those of health authorities. In other words, it would safeguard their independence. Scally is therefore wrong to suggest that the net effect of several of my recommendations would be to reduce the independence of the public health report. The whole thrust of my report is towards a more independent public health function. In arguing for reorganisation of the public health infrastructure (with some prescience, as it turns out) I propose a distinct pyramidal structure independent of the NHS Executive whose “ethos would be one of independence to monitor and publicly criticise not only Department of Health policies, as implemented by health authorities, but any area of policy which has a bearing on health.” In commenting on the least substantial of my recommendations (that the reports could be published every two or three years instead of annually) Scally suggests that there is no shortage of public health issues to be tackled and that annual reports can and should be a catalyst to action. That is my point exactly. I propose low cost annual statistical updates and two or three yearly in depth reports yielding a minimum set of comparable data relevant to national policy initiatives, such as a strategy to tackle health inequalities. This is far from being the “greater government specification of content” which Scally sees as constraining. It would simply enable annual reports to be a tool for monitoring progress towards agreed targets appropriate to local populations. Directors of public health should be free to report on any issue they consider relevant to the public health, and I also propose designating the director of public health with the lead role in developing local, multisectoral strategies for health.

The Adnexal Mass: Benign or Malignant? Evaluation of a Risk of Malignancy Index

OBJECTIVE To validate a risk of malignancy index incorporating menopausal status, serum CA 125 level and pelvic ultrasound features in the pre-operative diagnosis of ovarian cancer. DESIGN A retrospective observational study. SETTING Department of Obstetrics and Gynaecology, The Royal London Hospital. SUBJECTS One hundred and twenty-four women admitted consecutively to the gynaecology department for surgical exploration of an adnexal mass. MAIN OUTCOME MEASURES The sensitivities and specificities of menopausal status, serum CA 125 level and ultrasound features, in isolation and combined (the risk of malignancy index (RMI)), for diagnosing ovarian cancer. RESULTS Tested on a new population of women, the RMI retained the high sensitivity for diagnosing ovarian cancer seen in the original report describing its derivation. The specificity, however, was lower. The study confirmed that the RMI is more accurate than the individual criteria in diagnosing ovarian cancer, and was comparable with other scoring systems. CONCLUSIONS The risk of malignancy index is a simple scoring system for ovarian cancer. Application of the risk of malignancy index in clinical practice may provide a rational basis for specialist referral of patients with ovarian cancer before diagnostic surgery.