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Comment and Controversy

Don’t rush to adopt UK screening algorithm for ovarian cancer

September 2009 · Vol. 21, No. 09
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Dr. Kaunitz posits that ovarian cancer screening may be effective in postmenopausal women—but even that equivocation may be too strong an endorsement of the practice. Although the UK study he mentions was large and very well designed, the algorithm it employed is not necessarily applicable to US practice.

The multimodal screening algorithm required the 4,315 women who had an initial abnormal CA-125 level to wait 12 weeks before the screen was repeated. When it was, 1,008 women had abnormal results again and had to wait another 12 weeks for a third screen. This waiting period is critical because it is the constant rise in CA 125, rather than the absolute value of the marker, that is associated with ovarian cancer.

Ninety-six women in the UK trial were deemed to be at intermediate risk of ovarian cancer and underwent ultrasonography 6 weeks later, approximately 7 months after the first abnormal blood test. Of the 97 women in the study who underwent surgery, 42 had ovarian or tubal malignancy, but only 16 were earlystage (I/II). Therefore, six surgeries were performed to detect each case of early ovarian cancer, and early intervention should have made a difference in survival. However, within a year of screening, four additional women developed ovarian cancer (false negatives).

Surgery is not without risk in postmenopausal women; indeed, 3% of women in the UK study suffered major complications, including pulmonary embolus, deep venous thrombosis, hemorrhage, wound dehiscence, perforation of a viscus, bowel obstruction, and bowel fistula.

Ovarian cancer is a terrible disease, and we sorely need to find an effective method of early detection. But recent evidence suggests that some serous “ovarian” cancers may originate in the distal tube and are, therefore, at an advanced stage at the outset and undetectable at an early stage using current screening modalities.

The bottom line, as the authors of the UK study and Dr. Kaunitz all acknowledge, is that it is too early to tell whether this screening algorithm will have a significant impact on mortality. In the UK study, the cost-effectiveness of screening and the psychosocial effects on participants during the prolonged waiting periods are still being evaluated, and are likely to be significant issues. Before we rush to reintroduce routine CA-125 testing, which so far has done more harm than good, we should understand that the complex UK study algorithm cannot be abbreviated or we will submit many women to unnecessary surgery. Until the complete analysis is available, avoiding CA-125 screening is prudent.

William H. Parker, MD
John Wayne Cancer Institute at Saint John’s Medical Center
Santa Monica, Calif

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