Screening for Ovarian Cancer: What We Know, What We Need to Know

Although the survival of women with advanced ovarian cancer has improved over the past several decades, the majority of those presenting with stage III/IV disease ultimately die.[1,2] Because early-stage ovarian cancer is associated with a substantially greater survival, the development of an effective screening strategy to detect the malignancy while it remains localized to the ovary (stage I) is a reasonable goal.

The Elusive Screening Test

Unfortunately, for a number of reasons, as discussed in the excellent review by Drs. Hensely, Castiel, and Robson, development of such a useful screening technique for ovarian cancer remains elusive. An ovarian cancer screening test would have to be highly sensitive and specific to identify women with this relatively uncommon malignancy (approximately 25,000 new cases in the United States each year). Of particular concern would be the false-positive tests that could lead to unnecessary surgery, potentially considerable morbidity, and the removal of a normal ovary.

Drs. Hensely, Castiel, and Robson appropriately conclude, “screening for women of average risk is not recommended.” However, they then add that “screening with twice yearly transvaginal sonography and serum CA-125 testing is recommended for women at high risk for ovarian cancer.” This recommendation is apparently based on “expert opinion.”

To Screen or Not to Screen

What data support this conclusion? Is there any evidence that twice yearly transvaginal sonography and serum CA-125 will improve the chances of detecting early-stage disease, or that survival will be prolonged? The authors note that no such data exist. Furthermore, they discuss their own preliminary findings from a study of screening in high-risk women at Memorial Sloan-Kettering Cancer Center, which suggest that “anxiety may be exacerbated by false-positive test results.” Yet they apparently support the recommendation for screening based on “expert opinion.”

I believe it is appropriate to seriously question the recommendations of these “experts.” The fact that a woman has a significant risk for developing a serious and potentially fatal malignancy is strong justification to study the value of a variety of management strategies, including screening. However, in my opinion, this legitimate concern is insufficient reason to recommend an unproven, anxiety-provoking approach that has yet to demonstrate any impact on survival.

Removing the Ovaries as a Preventive Measure

How many women will have their ovaries removed based on nonspecific CA-125 elevations or “ultrasound abnormalities” read by clinicians (radiologists, gynecologists, family practice physicians) who are not experts in the radiographic interpretation of subtle changes in the structure of the ovary? Moreover, the emotional impact on women who obtain these tests every 6 months for several decades of their lives would be considerable. While “negative test results” may provide reassurance that “everything is okay,” are there data available to suggest this would be an accurate interpretation of such findings?

If screening is not able to reduce the risk of death from ovarian cancer, are there other methods that may effect a favorable outcome, at least at the societal level? Routine removal of the ovaries in postmenopausal women undergoing elective abdominal procedures (eg, gallbladder surgery, hysterectomy for fibroid disease) has been shown in large population-based studies to have the potential to produce a profound reduction in the risk of ovarian cancer.[3] Other data suggest that tubal ligation can substantially reduce an individual woman’s risk for the development of this malignancy.[4,5]

I agree with the statement that it is reasonable to recommend removal of the ovaries in a woman at high risk for ovarian cancer (based on genetic considerations), at an appropriate time in her life (ie, following childbearing). However, the performance of such a procedure does not eliminate the risk of developing an ovarianlike malignancy—ie, a primary carcinoma of the peritoneum. Thus, a woman contemplating removal of her ovaries for the specific purpose of preventing ovarian cancer must be carefully counseled regarding her continued risk for cancer and the possible but nonquantifiable benefits associated with this surgery.

References:

1. Partridge EE, Phillips JL, Menck HR: The national cancer database report on ovarian cancer treatment in United States hospitals. Cancer 78:2236-2246, 1996.

2. McGuire WP, Hoskins WJ, Brady MF, et al: Cyclophosphamide and cisplatin compared with paclitaxel and cisplatin in patients with stage III and stage IV ovarian cancer. N Engl J Med 334:1-6, 1996.

3. NIH Consensus Development Panel on Ovarian Cancer: NIH consensus conference. Ovarian cancer—Screening, treatment, and follow-up. JAMA 273:491-497, 1995.

4. Hankinson SE, Hunter DJ, Colditz GA, et al: Tubal ligation, hysterectomy, and risk of ovarian cancer. JAMA 270:2813-2818, 1993.

5. Banks E, Beral V, Reeves G: The epidemiology of epithelial ovarian cancer: A review. Int J Gynecol Cancer 7:425-438, 1997.