Early Detection of Ovarian Cancer in High Risk and General Risk Populations

Steven J. Skates, PhD, Associate Professor, Medicine, Harvard Medical School, Associate in Biostatistics, Cancer Center, Massachusetts General Hospital​

When Apr 25, 2017 from 03:30 PM to 04:30 PM (EST / UTC-400)
Where 3005 Michael Hooker Research Center
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Over 75% of ovarian cancers are detected in late stage disease with poor prognosis while if detected in early stage prognosis is often excellent. Despite therapeutic advances, the mortality rate has not changed over the past 50 years. This makes early detection an appealing approach to investigate for its potential to reduce ovarian cancer mortality.

Screening trials starting in 1985 tested serum CA125 annually, a newly discovered blood test for monitoring ovarian cancer therapy. Women with CA125 exceeding a threshold were referred to transvaginal ultrasound and additional CA125 tests. This multi-modal approach attained an acceptable positive predictive value (PPV) however greater sensitivity for early stage disease remained a significant concern. Analysis of longitudinal CA125 values from these trials indicated that most cases had exponentially rising CA125 from a baseline while most non-cases had relatively flat CA125 profiles. Utilizing this differential behavior increased sensitivity while maintaining the same PPV. This increase was achieved by calculating the probability of having a change-point given age and one or more CA125 values and making all screening decisions on the basis of this risk instead of her latest CA125 level. This approach establishes a baseline for each woman and detects significant rises above it, essentially using each woman as her own control.

In 1996, the first of five screening trials implemented this risk calculation in general population post-menopausal women and in women at increased genetic risk. In the general risk population trials, the risk of ovarian cancer algorithm measured CA125 annually and referred women with intermediate risks to an additional CA125 test in 3 months, and women with elevated risks to an immediate ultrasound. In the high-risk population, CA125 was measured more frequently (3-4 times per year), intermediate risk referred women to ultrasound, and elevated risk to ultrasound and review by a specialist physician. All trials implementing the risk of ovarian cancer algorithm showed a significant increase in early stage detection. No other ovarian cancer screening trials in the general or high-risk populations have achieved this result.