Early Detection of Ovarian Cancer: Normal Risk Ovarian Cancer Screening Study 2
Dr. Robert C. Bast and Dr. Denise Nebgen
At present there is no reliable screening test for ovarian cancer. In those cases where disease is detected while still confined to the ovaries (Stage I) or to the pelvis (Stage II), 70-90% of patients survive five years and two thirds can be cured. When disease has spread throughout the abdomen (Stage III) or to other parts of the body (Stage IV), fewer than 50% survive five years and fewer than 20% of patients can be cured. Currently, fewer than 30% of women with ovarian cancer are diagnosed in early stage (I-II). Computer simulations suggest that if we could increase the fraction of ovarian cancers detected in early stage, we could cure 10-30% of women with currently available surgery and chemotherapy.
Over the last two decades, MD Anderson has conducted a screening trial in more than 7,800 postmenopausal women at average risk for ovarian cancer. In this study, a single blood test (CA125) was measured each year to total more than 50,000 woman-years observed. We did this because science shows the CA125 protein tends to rise in the blood of women with progressively growing cancers — but not in women with benign conditions. To that end, when blood levels of CA125 have risen in screening participants, a transvaginal ultrasound has been performed. Abnormal ultrasound results prompted operations in 34 women, and 17 ovarian cancers were diagnosed, with 70% in early stage as a result of these screening methods.
Using the same approach, patients diagnosed with late-stage ovarian cancer have been reduced by 30-34%, compared to other ovarian cancer screening trials that have reduced late-stage disease by no more than 14%. Now it is time to build on this foundation and take the research to greater heights, using four blood tests rather than one to detect cases missed by CA125. A new computer program has been developed to combine all 4 tests. Using this program, we could have detected advanced-stage cases 1.4-to-4-years earlier, at a time before the cancer could spread.
The four-year Early Detection of Ovarian Cancer: Normal Risk Ovarian Cancer Screening Study 2 (NROSS2) trial is just beginning. The more than 4,000 postmenopausal women currently participating in the CA125 screening trial will be reconsented to participate in the new four-biomarker trial. We will recruit an additional 500 women to permit an accurate assessment of the percentage of patients requiring ultrasound and the number of operations required to detect each case of ovarian cancer. The four blood tests will be measured each year in postmenopausal women who have an average risk of developing the disease. Blood levels from the four tests will be analyzed with the new computer program to determine whether there is enough of a rise across the four tests to represent an increased risk. We estimate about 2% of women with rising risk will then undergo ultrasound exams of the ovaries and, if an abnormality is found, this may prompt surgery. Proof of concept could lead the way to an effective screening strategy for this disease.