39,105 women were randomized to the intervention arm. Women who had their first abnormal suspicious screen and received both tests in that same year, and had at least two years of follow-up are included. 3,224 women met these criteria (). 1611 women had an abnormal result at the T0 screen, 543 underwent surgical intervention and 25 invasive cancers were detected. During the T1+ screening years, 1,613 additional women had an abnormal result. Of these, 329 underwent surgical evaluation and 34 additional invasive cancers were detected. None of the 34 women who were detected with cancer in the T1+ screen had positive screens at T0. Five of these women had abnormal non-suspicious transvaginal ultrasounds at T0 and 3 women did not have CA 125 done at T0. The overall probability of cancer detection following an abnormal screen was 1.6% (CI 0.9–2.2) at T0 and 2.1% (CI 1.4–2.8) during T1+.
Flow of patients through the ovarian intervention arm of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.
shows an analysis of the relationship of size and morphology of abnormalities found on transvaginal ultrasound to the positive prediction of cancer at T0. If no solid or mixed, irregular, or papillary components are present, the risk of cancer is low, independent of the size of the abnormality. Similarly, a cyst less than 5 cm has a low risk of being cancer regardless of the morphology. However, a cyst of 5 cm or more with mixed, papillary or irregular components places a woman at uncertain risk. Size and morphology alone do not identify a high risk category.
Risk of Cancer at Initial Screen Based on Size and Morphology
Predictive values for the combination of CA 125 level and transvaginal ultrasound status are shown in . If the transvaginal ultrasound is negative, a CA 125 <60 falls in the range of low risk (0.0% CI 0.0%–0.3%), 60–70 is uncertain risk (4.6% CI 2.9%–7.9%), and over 70 is high risk (15.9% CI 14.7%–17.7%), A positive transvaginal ultrasound with a negative CA 125 is low risk (0.7% CI 0.7%–0.8%). A combination of abnormal transvaginal ultrasound and abnormal CA 125 is high risk (25.0% CI 23.3–27.3%).
Risk of Cancer at Initial Screen Based on CA 125 and Transvaginal Ultrasound
During T1+ we were able to compare current to previous ovarian/cyst size and CA 125 levels. compares transvaginal ultrasound and CA 125 change. As in T0, the combination of abnormal results for both CA 125 and transvaginal ultrasound predicts a high risk for cancer (42.9%, CI 40.9%–46.0%). With a negative transvaginal ultrasound, the magnitude in change in CA 125 is predictive. A change of 25 or less predicts a low risk (0.3% CI 0.2%–0.5%) while a change of 45 or more predicts a high risk (29.0% CI 28.3%–30.3%). A change of 25–45 was low for risk for cancer (1.7% CI 1.4%–2.4%). If the transvaginal ultrasound is positive, increases in CA 125 may indicate an elevated risk for ovarian cancer even when the CA 125 remains normal (<35). In this situation, an increase of >10 trends toward a high risk (10.0% CI 7.9%–13.9%), although lower limit of CI is less than 10%. A CA 125 change <10 predicts a low probability of cancer (0.2% CI 0.15%–0.3%).
Risk of Cancer in Subsequent Screens Based on CA 125 and Transvaginal Ultrasound
takes into account changes in cyst or ovarian size in women with abnormal transvaginal ultrasound, but normal CA 125. A change in size of 6 cm or greater suggests the possibility of high risk (13.3% CI 10.5%–18.0%) whereas a change in size <6 cm is low risk.
Risk of Cancer in Subsequent Screens Based on Change in Cyst or Ovary Size
For T0, using the high risk criteria of transvaginal ultrasound negative with a CA 125 of ≥ 70, or a CA 125 and a transvaginal ultrasound positive, the sensitivity for detection of cancer within the PLCO data is 60%, the specificity is 96.2%, PPV is 19.7% and NPV is 99.3%.
For T1+ using three high-risk criteria – transvaginal ultrasound-negative with a change in CA 125 > 45; CA 125 negative, but a change in diameter of ≥ 6 cm; or both CA 125 and transvaginal ultrasound-positive – the sensitivity for detection of cancer within the PLCO data is 85.3%, specificity 95.6%, PPV 29.6% and NPV 99.7%.