General Departmental Seminar Series
UW Comprehensive Cancer Center Grand Rounds
Screening for Ovarian Cancer with Serum Biomarkers
Stephen Skates, PhD, Assistant Professor, Harvard University and Massachusetts General Hospital
Wednesday, January 15, 2003, 8-9 a.m.
G5/113 Clinical Sciences Center, 600 Highland Ave.
Ovarian cancer is most often diagnosed in late stage (75%) when prognosis is very poor. In contrast, when it is diagnosed in early stage disease, prognosis is excellent, with five year survival exceeding 90% for well differentiated tumors. This contrast makes early detection of ovarian cancer through mass screening programs an appealing approach to investigate for the reduction of ovarian cancer mortality. Since definitive diagnosis and treatment requires invasive surgery, the literature has suggested that an ovarian cancer screening program is acceptable if at most ten surgeries are required for each ovarian cancer detected, or a positive predictive value (PPV) exceeding 10%. Since ovarian cancer has a relatively low annual incidence, varying between 1 in 2,000 and 1 in 2,500 women in post-menopausal women, extremely high specificity (>99.6%) and high sensitivity (> 75%) is required for the PPV to exceed 10%. In ovarian cancer screening trials with CA125, a serum biomarker, as the first line test, followed by ultrasound for elevated levels of CA125, the PPV was 22%, demonstrating that the sequential application of a blood test and an imaging test had the required specificity and pre-clinical sensitivity. However, the sensitivity for early stage disease was only 40%. Statistical analysis of longitudinal CA125 levels indicated that the CA125 profile added substantial information about the presence of undiagnosed ovarian cancer compared to absolute CA125 levels at a single point in time. A statistical method was developed for incorporating this information into the screening process, and implemented in a randomized screening trial in the UK. Preliminary results from the trial were sufficiently encouraging to mount a definitive 10 year randomized trial of ovarian cancer screening on 200,000 post-menopausal women beginning in 2001. Using a similar serum biomarker approach, a two year pilot trial on screening high risk women for ovarian cancer was initiated in 2001 in the US by the Cancer Genetics Network (CGN), with additional collaboration from other groups and sites. This talk presents the development of the method, the implementation in the two clinical trials, and directions for further research in ovarian cancer screening.
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