Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective
Commentary by Associate Professor David Allen
The article:
Woodward ER, Sleightholme HV, Considine AM et al. Annual surveillance by CA125 and transvaginal ultrasound for ovarian cancer in both high-risk and population risk women is ineffective. BJOG 2007;114(12):1500-9. Published online 28 September 2007 doi:10.1111/j.1471-0528.2007.01499.x
The reviewer:
Associate Professor David Allen is Chief Medical Officer and Deputy Head of the Department of Gynaecological Oncology at the Mercy Hospital for Women in Victoria.
Summary
Abbreviations
Bilateral Salpingo-Oophorectomy (BSO), Cancer antigen 125 (CA125), Negative Predictive Value (NPV), Positive Predictive Value (PPV), Transvaginal Ultrasound (TVU)
Study Design
This retrospective study assessed the efficacy of annual CA125 and transvaginal ultrasound (TVU) scan as surveillance for ovarian cancer, using an audit of the patient case records, laboratory CA125 results, radiology reports, histology records and local cancer registry data. The study included 341 asymptomatic women who were enrolled for ovarian cancer screening between April 1996 and March 2005 at Birmingham Women’s Hospital, UK. The women in the study had reported a family history of ovarian cancer. Of those enrolled, 179 were classified as high-risk (>10% lifetime risk of developing ovarian cancer), 77 as moderate-risk (4–10% lifetime risk) and 71 as near-population-risk (<4% lifetime risk). The primary outcome of the study was the occurrence of ovarian cancer in the population. The performance of the surveillance tests were measured by sensitivity, specificity, PPV and NPV.
Findings
During the study period a total of 1084 surveillance TVU and 957 CA125 measurements were undertaken in the cohort. The performance measures of these tests are presented in Table 1. Among the study population 30 women underwent exploratory surgery due to abnormal findings during surveillance, of which two women had a cancer detected, one ovarian and one endometrial cancer. Three additional ovarian cancers were detected as interval cancers (all in premenopausal women with previous normal results from surveillance tests). The three interval cancers were all advanced stage and the one asymptomatic cancer detected by surveillance was also at least stage III indicating that screening is not detecting early stage cancers. Fifty-seven women had chosen to have prophylactic surgery, there were no ovarian cancers reported to the cancer registry following this surgery. No cancers were detected at the first screening episode and the women in whom ovarian cancer occurred had at least one normal screening episode prior to diagnosis.
Table 1. Performance of surveillance tests*
| Performance measure | Whole Cohort | High-risk women only | ||||
|---|---|---|---|---|---|---|
| CA125 alone | TVU alone | CA125 and TVU combined | CA125 alone | TVU alone | CA125 and TVU combined | |
| Sensitivity (%) | 50 | 33.3 | 66.7 | 50 | 33.3 | 50 |
| Specificity (%) | 98.1 | 85.8 | 82.9 | 98.2 | 84.5 | 82.8 |
| PPV (%) | 5.6 | 0.6 | 1.5 | 10 | 1.1 | 1.3 |
| NPV (%) | 99.9 | 99.8 | 99.8 | 99.8 | 99.6 | 99.7 |
NPV – negative predictive value; PPV – positive predictive value; TVU – transvaginal ultrasound
*(from Woodward et al, Table 8, page 1508)
Conclusion
The authors concluded that screening by annual TVU and CA125 does not detect early stage cancers in premenopausal women and that there is a high rate of false-positive results.
Commentary
What does this article add to existing clinical evidence in this area?
This article confirms the findings of other recent studies of ovarian cancer screening: screening is of limited value because of the number of false positive findings.
How adequate was the methodology used in addressing the aims of this study?
The aim of the study was to assess the efficacy of annual CA125 and transvaginal ultrasound (TVU) as surveillance for ovarian cancer. The study is a retrospective audit of 341 asymptomatic women who were placed in a high-risk, medium-risk or low-risk group. Most women were in the mixed high-risk group which included several different gene mutations or positive family histories. Although the statistical analysis is appropriate, the study suffers from being retrospective with small numbers and heterogenous groups.
What are the implications of this study for clinical practice in Australia?
There is more evidence for harm from ovarian cancer screening than there is for any benefit. The high false positive rates result in many surgical procedures being performed before an ovarian cancer is found. As with other studies, this study does not show any benefit or impact on mortality related to ovarian cancer.
TVU is invasive and expensive and needs highly trained and experienced operators. Pap smears for cervical cancer screening can be as invasive and suffer from high false negative rates, but have resulted in a dramatic decrease in the incidence and mortality from cervical cancer over the years. The same cannot be said for ovarian cancer screening at the present.
For the general population, there is no evidence to justify ovarian cancer screening with CA125 and TVU. Screening the premenopausal population is even more dubious with variations during the menstrual cycle showing up on TVU (ovarian size and physiological cysts) and CA125 levels (may be above normal levels during cycle). The postmenopausal group does not suffer from these variations. The high-risk women with gene mutations or strong family history more often than not fall into the premenopausal group (as in this study by Woodward et al).
Even in high-risk women, there is no solid evidence that ovarian cancer screening is of benefit. On the basis of present evidence, screening may even provide a false sense of security in this group. Microscopic or small volume ovarian cancers may be found during risk-reducing bilateral salpingo-oophorectomy (BSO), when CA125 and TVU were normal preoperatively. Screen-detected early stage ovarian cancers may be in the same category.
Until new data or new and more effective methods of screening emerge, we should concentrate on prevention rather than screening for women at high risk. This study included some women at low risk, with screening done every 12 months. Should high-risk women chose not to have risk-reducing surgery, they may benefit from six-monthly transvaginal ultrasounds, however, they should be counselled about the advantages and disadvantages of individual surveillance options.
Editor: Ms Jane Francis, Program Manager/Ovarian Cancer, National Breast and Ovarian Cancer Centre.
Editorial Committee: Prof Michael Friedlander – Medical Oncologist, Prof Neville Hacker – Gynaecological Oncologist, Dr Gillian Mitchell – Medical Oncologist, Dr Deborah Neesham – Gynaecological Oncologist, Ms Georgie Richter – Gynaecological Nurse.
Disclaimer
Clinical Update - Ovarian Cancer is produced by the National Breast and Ovarian Cancer Centre (NBOCC) and is intended to provide health professionals with timely expert commentary on new research in ovarian cancer. Commentaries included in Clinical Update - Ovarian Cancer do not replace recommendations included in NBOCC clinical practice guidelines.
Information contained in Clinical Update - Ovarian Cancer is not intended to be used as substitute for an independent health professional's advice. The NBOCC does not accept any liability for any injury, loss or damage incurred by use of or reliance on the information contained in Clinical Update - Ovarian Cancer. The NBOCC develops material based on the best available evidence however cannot guarantee and assumes no legal liability or responsibility for the currency or completeness of the information.
