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ABSTRACT: Confirmed doubling of CA125 value is one definition of progression in ovarian cancer patients. If asymptomatic, the management of these patients is unclear. To provide information which may assist in therapeutic decision making, we set out to determine the independent prognostic significance for the rate of rise in CA125 during surveillance in ovarian cancer patients as measured by CA125 doubling time. Clinical information was obtained through a 2-staged chart review of ovarian cancer patients treated in our department from 1994 to 2003. We searched for patients who met criteria for CA125 progression and doubling during surveillance following first-line therapy. A total of 296 patients were initially identified. During surveillance, the median doubling time of CA125 was 40 d and the median survival for patients with a CA125 doubling time of 40 d was 10.6 months compared to 22.1 months for those with doubling time>40 d. In a univariate analysis, age, high-grade, suboptimal cytoreduction, short CA125 doubling time, short time to progression and high CA125 at progression were significantly associated with poor survival, but in a multivariate analysis, a short CA125 doubling time of <or=40 d and a short time to disease progression (<or=180 d) were the only independent adverse prognostic factors (p=0.001). Second stage review identified 28 new patients who provided a confirmatory set that supported the adverse survival trend for patients with short CA125 doubling time. The rate of rise of CA125 during surveillance carries independent prognostic significance, and should be considered when making therapeutic decisions.