Similarly, a single-arm prospective study in the United States looking at a two-stage screening strategy using ROCA and TVUS showed comparable specificity and positive predictive values to those reported on UKCTOCS (Cancer 2013;119:3454-61). Consequently, multimodal screening resulted in significantly fewer surgeries performed to detect a case of cancer in both studies. However, survival studies are needed to supplement the U.S.-based trial, and the UKCTOCS study has not yet shown an improved survival in the "screened" population. The final results for the latter trial will not be available until 2015.
Ideally, a good screening test would decrease unnecessary operations because of the risks for serious complications that they carry. This was demonstrated by the randomized PLCO (Prostate, Lung, Colorectal, and Ovarian Cancer Screening) trial, in which multimodal screening (CA-125 and TVUS) was evaluated. Complications ("harms") from screening were one of the secondary outcomes. Screening led to surgery for almost a third of the women who had positive findings. Because the positive predictive value in this study was only 3.7%, many surgeries were performed for benign conditions. A total of 15% of the women who had surgery for a false-positive result experienced at least one serious complication. Furthermore, the increased harm did not come with improved detection or survival rates. The women in the screening arm had similar disease-specific and all-cause mortality as did the women in the nonintervention arm, and there was no difference in ovarian cancer stage at the time of diagnosis.
In summary, based on the significant potential harms without significant benefits, there is no role for the use of either CA-125 or ultrasound in screening for ovarian cancer in women without a suspected family history of hereditary ovarian cancer syndromes. This position has been endorsed by the U.S. Preventive Services Task Force, the Society of Gynecologic Oncology (SGO), and the American College of Obstetricians and Gynecologists (ACOG).
The benefit, or lack thereof, of ovarian cancer screening in women with BRCA1, BRCA2 mutations, or Lynch syndrome is less well defined, mainly because of the paucity of data. Randomized trials addressing screening are unlikely to be performed in this population because the low likelihood that any patient would agree to be in the no-screening arm. The small amount of evidence that exists does not show improved early detection and is consequently not very reassuring. However, given the high lifetime risk of these patients developing ovarian cancer, SGO, AGOG, and the National Comprehensive Cancer Network recommend routine screening with CA-125 and TVUS every 6 months starting at age 30-35 years old or 5-10 years before the age of first diagnosis in the family.
In conclusion, the current evidence suggests that the harm of screening for ovarian cancer with CA-125 and ultrasound outweighs the benefits in women at average risks for the development of the disease. Thus, screening in this group is neither effective nor indicated (N. Engl. J. Med. 2009;361:170-7). In women with hereditary ovarian cancer syndromes, screening is encouraged, although we currently lack evidence that early detection or survival will be improved. Further research is needed in order to develop safer, more reliable, and cost-effective screening strategies.
Dr. Clarke-Pearson is the chair and the Robert A. Ross Distinguished Professor of Obstetrics and Gynecology, and a professor of in the division of gynecologic oncology at the University of North Carolina, Chapel Hill. Dr. Roque is a fellow in the gynecologic oncology program at the University of North Carolina. Neither Dr. Clarke-Pearson nor Dr. Roque has any relevant financial disclosures. E-mail them at obnews@frontlinemedcom.com.