Venous thromboembolism in ovarian cancer: incidence, risk factors and impact on survival

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Abstract

Objectives

Ovarian cancer has a higher incidence of venous thromboembolism (VTE) than other cancers. Clear cell cancers carry the highest risk at 11–27%. The aim of this study was to identify the predisposing factors for VTE in a population of ovarian cancer patients and to determine the influence of VTE on overall survival.

Study design

VTE events were identified from hospital and general practice/community care records for all patients with ovarian cancer who were diagnosed and treated in a tertiary cancer center between 2006 and 2010.

Results

The overall incidence of VTE was 9.7% (33) in 344 patients. Sixteen (48%) had pulmonary embolism. Six (18%) presented with VTE. Five (15%) had VTE diagnosed during pre-treatment routine CT scanning. Eleven (33%) developed VTE following surgery and eleven (33%) developed VTE during chemotherapy. Risk factors associated with the occurrence of VTE were BMI  30 (p < 0.01), clear cell carcinoma (p < 0.05), advanced stage (p < 0.01), high grade (p < 0.01) and CA125 > 500 IU/ml (p < 0.001). The occurrence of VTE was associated with decreased overall survival time (p < 0.001).

Conclusion

The incidence of VTE is high in ovarian cancer especially in the clear cell subtype. VTE adversely affects survival in ovarian cancer. Obesity, high grade and stage of cancer, clear cell subtype and high CA 125 level should be incorporated into protocols of VTE prophylaxis in women with ovarian cancer.

Introduction

The close two-way clinical relationship between cancer and venous thromboembolism (VTE) has been known since Trousseau's time [1]. Vascular endothelial damage, stasis of blood flow and hypercoagulability are the three arms of Virchow's triad and cancer is known to affect all three. Ovarian cancer has been shown to have a high incidence of VTE compared to other cancers [2], with clear cell carcinoma carrying the highest incidence of 11–27% [3], [4], [5]. The cause of this increased risk of VTE is multifactorial, with reduced physical activity, chemotherapy, extensive cytoreductive surgery and release of procoagulant factors from cancer cells contributing to the risk [6]. The diagnosis of VTE is often the first symptom of occult malignant disease and has been shown to significantly affect overall survival in patients with ovarian cancer [7], [8].

Factors contributing to the risk of VTE in cancer can be divided into patient-, cancer- and/or treatment-related. Advanced age [9], comorbidities [10], history of prior VTE and prolonged immobility [11] increase the risks of VTE. Cancer induces a hypercoagulable state [12], the severity of which is related to the type, stage, grade and location of the cancer [4], [13]. Chemotherapy [14], [15], surgery [16] and the newer anti-angiogenesis agents [17] used in the treatment of ovarian cancer are associated with an increased risk of venous thrombosis.

In line with these findings, recent guidelines advise extended low molecular weight heparin (LMWH) prophylaxis following surgery for gynecological cancers beyond the patient's hospital stay [18]. LMWH is not without risk, however, and thrombocytopenia and heparin-induced thrombosis (HIT) are examples of complications of heparin treatment. Identification of risk factors for VTE will aid in selection of patients for extended prophylaxis.

We investigated the incidence of VTE in a population of ovarian cancer patients treated in our center between 2006 and 2010 prior to adoption of extended prophylaxis. Our objective was to determine the predisposing factors for VTE in our population and to determine the influence of VTE on overall survival in ovarian cancer patients.

Section snippets

Patient population

Data from all patients diagnosed and treated for ovarian cancer from January 2006 to December 2010 in St James's Hospital Gynaecology Oncology Unit were extracted from the gynaecology oncology database. The database records all patient demographic features, type of cancer (histology, stage, grade), treatment received (type of surgery, chemotherapy), laboratory results and significant events arising during the follow-up period. General practice/community records were checked to confirm accuracy.

Patient demographics

Three hundred and fifty patients were identified from the database. Six patients were excluded, one because clinical details were incomplete and five who were on long term anticoagulant therapy, and 344 patients were included in the final analysis. Follow up data were available for 12 and 60 months following the diagnosis of ovarian cancer.

The median (IQR) age of the patients was 57 (48–67) years: 21% of patients had a BMI equal to or more than 30 kg/m2. The histology types were borderline (n = 

Comments

Gynecological malignancies and ovarian cancer in particular are associated with high rates of VTE. The treatment and prevention of VTE are challenging in these patients after major surgery, as pelvic surgery itself is an additional risk factor for VTE. Although the introduction of LMWH prophylaxis has reduced the incidence of VTE in ovarian cancer patients, some patients develop VTE despite anticoagulation and there is uncertainty as to the requirement for protracted prophylaxis for all or some

Conflict of interest

None of the authors has a conflict of interest.

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