Our study demonstrated the highest incidence of VTE during the total follow-up period and during the first 6 months occurred in women with endometrial cancer administered chemotherapy as a primary cancer treatment. The monthly incidence of VTE decreased with time during the first year in the no treatment, surgery, and hormone therapy groups but did not change in the radiotherapy or chemotherapy groups. Furthermore, the risk of VTE was greater for women that underwent chemotherapy or hormone therapy than for those that received no treatment.
Reported incidences of VTE in women with endometrial cancer range between 0.35 and 8% [6, 7, 9,10,11,12,13, 15, 16, 25]. In the present study, VTE incidences agreed with those previously reported (1.4% during the total follow-up period and 0.5% during the first 6 months). In one cohort study, the absolute rate of VTE in women with endometrial cancer (n = 1958) decreased over time after cancer diagnosis . In another two cohort studies, the incidence of VTE decreased over time for 30 (n = 175) and 90 days (n = 4158) following gynecologic cancer surgery [27, 28], and in a fourth cancer cohort study conducted on a claims database (n = 17,284), the incidence of VTE decreased over time during the 12 months following the initiation of chemotherapy . Similarly, we found that in the no treatment, surgery, and hormone therapy groups, the incidence of VTE decreased with time during the first year after primary cancer treatment initiation. However, in our radiotherapy and chemotherapy groups, no longitudinal change in the incidence of VTE was observed. Further studies are needed to clarify VTE occurrence trends with respect to time for different primary cancer treatment types.
Previous studies have reported incidences of 0.35–8% for VTE in women with endometrial cancer that have undergone surgery (open or minimally invasive surgery including staging surgery) [6, 7, 9,10,11,12,13, 15, 16], and incidences of 0–13.8% in women with ovarian, cervical, or endometrial cancer that have undergone surgery [5,6,7,8,9,10,11,12,13,14,15,16]. In one cohort study, VTE occurred in 1.2% of women that had undergone gynecologic brachytherapy for cervical, endometrial, or vaginal cancer (n = 329) , and in a claims database analysis of women with ovarian cancer (n = 1880), the incidence of VTE was reported to be 11% during the first year after the initiation of chemotherapy . In a cohort study performed on women with cervical cancer (n = 798), the incidence of VTE was 33.8% among women that received chemotherapy, and chemotherapy was found to be a risk factor of VTE . In another cohort study performed on women with ovarian cancer (n = 328), non-receipt of treatment for cancer was a risk factor of VTE . In our study, the incidence of VTE was highest for chemotherapy (2.4%) followed in decreasing order of frequency by hormone therapy (1.6%), no treatment (1.3%), surgery (1.3%), and radiotherapy (1.1%) during the total follow-up period, and chemotherapy (1.6%), radiotherapy (0.7%), surgery (0.6%), no treatment (0.6%), and hormone therapy (0%) during the first 6 months of follow-up. Furthermore, compared with women that received no treatment, VTE risk, especially for PE, was significantly higher in women that received chemotherapy or hormone therapy during the total follow-up period and was significantly higher for women that underwent chemotherapy at six-month follow-up visits. It has been reported that sudden fatal PE event is a leading cause of VTE-related deaths in medical and surgical patients . Current guidelines recommend that anticoagulant treatment for VTE prophylaxis during systemic chemotherapy may be considered for ambulatory cancer patients at intermediate or high risk of VTE (Khorana score ≥ 2) [4, 31, 32]. Furthermore, gynecologic cancers are considered high risk by the Khorana predictive model for chemotherapy-associated VTE , and women with endometrial cancer that receive chemotherapy as a primary treatment usually have advanced disease and are at high risk for VTE [4, 20]. Therefore, our findings that chemotherapy as a primary therapeutic modality is a risk factor of VTE and associated with the highest incidence of VTE support the use of anticoagulants to prevent chemotherapy-associated VTE in women with endometrial cancer that receive chemotherapy as a primary treatment.
In a study of women with endometrial cancer treated by surgical staging (n = 714), the incidence of VTE was greater in women older than 60 years than in women younger than 60 years (10.7% vs 7.1%) . Similarly, in another endometrial cancer cohort (n = 1958), the absolute rate of VTE was higher in women over 60 years than in women under 60 years (13 per 1000 person years vs 7 per 1000 person years) . In our study, regardless of follow-up duration after primary treatments initiations, women with VTE were older than women without, and the risk of VTE increased with age. In addition, we observed changes in VTE occurrence according to primary treatment type and age. Interestingly, for all types of primary treatment, except hormone therapy, we found the incidence of VTE decreased from 70 or 75 years of age. We suggest this finding be confirmed by further study.
In our study, 14.5% of women with endometrial cancer underwent prophylactic anticoagulant treatment during the total follow-up period, and the incidence of VTE were higher in those that received prophylactic treatment. We believe that women exposed to VTE risk factors such as old age, high CCI, radical hysterectomy, chemotherapy, or hormone therapy are likely to receive prophylactic anticoagulant treatments more frequently.
This nationwide, population-based cohort study provides more data than multicenter studies. Furthermore, it is the first to evaluate the incidence and risk of VTE in a large cohort according to primary treatment in women with a diagnosis of endometrial cancer and to examine relationships between chemotherapy or hormone therapy and VTE. Limitations of this study are associated with analysis using claims data. First, diseases were defined using diagnostic and prescription codes, and medical records were not reviewed, and thus, a few women coded incorrectly may have been misdiagnosed. Second, women that received prescriptions for anticoagulants less than twice were not considered to have VTE. Based on the coverage provided by the Korean national health insurance system, women with VTE are usually treated regardless of symptoms, and thus, we believe only a small proportion of those affected were not treated for VTE. Third, women with VTE before endometrial cancer diagnosis or initiation of primary cancer treatments were not included. If diagnosis of VTE or endometrial cancer and initiation of primary cancer treatment occurred within a short time frame, it is possible that the order of diagnosis was inaccurate. Finally, we did not evaluate relationships between VTE and BMI or stage or histologic type of endometrial cancer because the HIRA dataset did not provide this information. Nonetheless, our study indicates primary treatment presents a greater risk of VTE than no treatment, which might be because of the dependence of treatment modality on stage.
This retrospective analysis of claims data presents the incidence and risk of VTE and time to VTE occurrence according to primary treatment type in women with endometrial cancer. We hope that the results of this study help guide the prophylaxis and treatment of VTE, which is a serious complication in women with endometrial cancer.