Objectives: To determine the incidence, time course, and risk factors associated with the development of venous thromboembolism (VTE) and the effect of VTE on survival in women with uterine cancer.

Methods: Using the California Cancer Registry, the date, stage, and histology of all incident uterine cancer cases during 1993-1999 were identified. These cases were linked with the state's hospital discharge database, allowing identification of incident VTE events, after excluding cases with a previous history of VTE. Proportional hazards modeling was used to analyze the association of baseline risk factors with the development of VTE (<1 year), using major surgery as a time-dependent covariate. In a similar model for death (<2 years), VTE was included as a time-dependent covariate.

Results: Among 18,440 cases with uterine cancer, the 2-year cumulative incidence of VTE was 2.7%. The cumulative incidence varied from 1.5% among women with local stage disease to 10.5% among women with advanced disease. Among cases diagnosed with local disease, risk factors for the development of VTE within 1 year in localized disease included major surgery (hazard ratio [HR] = 2.1, P < 0.01), presence of long-term comorbidities (HR = 2.9 for ≥3 comorbidities, P < 0.0001), black race (HR = 2.0, P < 0.006), and sarcoma histology (HR = 1.7, P < 0.04). Among cases with regional disease, presence of comorbidities, black race, and sarcomas or nonendometrioid carcinomas were all associated with significantly higher risk of VTE. In advanced disease, the presence of any comorbidities and black race were the strongest predictors (HR = 2.4 and 1.9, respectively). Women (aged <45 years) with advanced disease had a notably high 2-year incidence of 18%. Age did not predict VTE in localized and regional diseases. For all stages of cancer, development of VTE within 2 years was a significant predictor of decreased survival, and the magnitude of the risk was greatest among the cases diagnosed with localized disease (HR = 6.1; confidence interval, 4.6-8.1).

Conclusions: The incidence of VTE in women with uterine cancer was high, particularly in younger women with metastatic disease. The strong association between development of VTE and death suggests a close coupling between the biological aggressiveness of the cancer and the activation of thrombosis.