The National Comprehensive Cancer Network currently recommends ovarian screening for women at high risk. NCCN guidelines state that screening should be done with ultrasound, transvaginal ultrasonography, and CA125 serum marker testing every six months starting at age 35 or, depending on the family history, five to 10 years before the earliest diagnosis of ovarian cancer.
So if recommendations are in place, and high-risk women face a greater risk of dying from ovarian disease, why is there any argument about whether screening has value in these women? One issue is that, in the general population, ovarian cancer is relatively uncommon, and most data on ovarian cancer disease progression come from this larger pool of women. Also, the current tests for early detection are simply not sensitive enough to be used as screening tools in a general population.
Presented by DR. BETH KARLAN
|•||Screening high-risk women could downstage them from being stage III and IV patients to being stage I and II patients, thereby improving the chance of long-term survival.|
|•||Data from the 22,000-woman pilot study demonstrated that screening could improve survival compared with a control group.|
|•||Data from UKCTOCS showed that multimodality screening meets the minimum standard of a 10% PPV.|
|•||Numerous biomarkers have been identified as potential candidates for early diagnosis.|
Nonetheless, high-risk women should be judged by a different set of rules. Screening in this population could effectively lower these women's risk of having late-stage disease, said Beth Karlan, MD, arguing in favor of routine screening. Taking the opposite stance was Michael Birrer, MD, PhD, who emphasized that the current understanding of ovarian cancer and the tools for early detection do not meet the accepted criteria for sound screening.
Dr. Karlan is the Board of Governors Endowed Chair of Gynecologic Oncology and director of the Women's Cancer Research Institute at the Samuel Oschin Cancer Institute at Cedars-Sinai Medical Center in Los Angeles. She also is director of the division of gynecologic oncology at the Gilda Radner Cancer Detection Program at Cedars-Sinai. She is a professor of obstetrics and gynecology at the Geffen School of Medicine, University of California, Los Angeles.
Dr. Birrer is the director of gynecologic medical oncology at Boston's Massachusetts General Hospital Cancer Center. He is also co-chair of the National Cancer Institute's Gynecologic Cancer Steering Committee and chair of the committee on experimental medicine for the Gynecologic Oncology Group (GOG).
Current screening techniques are good enough
Women who have inherited a deleterious mutation (BRCA) are at a very high risk for ovarian cancer, more than an order of magnitude greater than the general population, Dr. Karlan said. When these high-risk women do present with disease, it is often metastatic and widespread, putting them at an equally high risk of dying from ovarian cancer.
"If we had a means of finding the ovarian cancer earlier, we could move a portion of those stage III and IV patients to stage I and II, and we could significantly improve the survival of women with ovarian cancer, even without any new therapies," Dr. Karlan said. "Today, survival of stage I ovarian cancer already exceeds 90% so ovarian cancer screening makes sense. It's a highly lethal disease that when caught early can be cured."
Dr. Karlan cited data from a pilot trial of 22,000 women who where randomized either to a control group or to an intervention group. The latter were offered three annual screening exams with CA125 testing; pelvic ultrasonography if CA125 was 30 U/mL or more; and referral for further examination if the ovarian volume was 8.8 mL or more on ultrasonography. All of the women were followed to see whether they developed invasive epithelial cancers of the ovary or fallopian tube (index cancers).
According to the results, 29 of the 468 women in the screened group with an elevated CA125 level were referred for a gynecologic opinion; screening detected an index cancer in six, and 23 had false-positive screening results. The positive predictive value was 20.7%. During a seven-year follow up, ten women with index cancers were identified in the screened group and 20 in the control group. The median survival of women with index cancers in the screened group was 72.9 months vs 41.8 months in the control group (P = .0112). However, 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 (Lancet 353:1207-1210, 1999).
Dr. Karlan acknowledged that "this was a pilot study and it was not powered to determine a difference in mortality. However, if you looked at the data, those in the screening group had survival that was almost twice that of the control group."