ObjectiveTo enhance cost-effective management of uterine cancer by predicting the likelihood of extrauterine disease and survival on the basis of preoperative parameters.MethodsA retrospective review of preoperative CA 125 levels from 210 women with endometrial carcinoma was performed. The relationship of preoperative CA 125 levels to various preoperative and postoperative histopathologic factors was investigated.MethodsElevated CA 125 (greater than 35 U/mL) correlated (P< .05) with higher stage, higher grade, increased depth of myometrial invasion, positive cytology, pelvic or para-aortic lymph node metastases, and reduced actuarial survival (P< .001). Multivariate analysis of preoperative factors showed that an elevated CA 125 level was the most important predictor for poor survival (P< .001). Moreover, a preoperative CA 125 level greater than 65 U/mL was the most significant predictor of extrauterine disease and carried a 6.5-fold higher risk (95% confidence interval 2.5, 17.1). A logistic model to predict extrauterine disease was developed. The model has a sensitivity of 62%, specificity of 91%, positive predictive value of 69%, and negative predictive value of 88%.ConclusionA CA 125 level should be included as part of the preoperative workup for all patients with uterine cancer. Patients with a preoperative CA 125 level less than or equal to 20 U/mL should be considered as candidates for vaginal hysterectomy unless unfavorable histology or a high-grade (grade II or III) tumor is present. In our series, this approach would have eliminated 24% of the abdominal staging procedures, with a risk of less than 3% for extrauterine disease, while lowering treatment-related morbidity and cutting costs in the treatment of this common female cancer.