Venous thromboembolism in metastatic urothelial carcinoma or variant histologies: incidence, associative factors, and effect on survival

Abstract

Venous thromboembolism (VTE) is common in cancer patients. However, little is known about VTE risk in metastatic urothelial carcinoma or variant histologies (UC/VH). We sought to characterize the incidence, associative factors, including whether various chemotherapy regimens portend different risk, and impact of VTE on survival in metastatic UC/VH patients. Patients diagnosed with metastatic UC/VH from 2000 to 2013 were included in this multicenter retrospective, international study from 29 academic institutions. Cumulative and 6‐month VTE incidence rates were determined. The association of first‐line chemotherapy (divided into six groups) and other baseline characteristics on VTE were analyzed. Each chemotherapy treatment group and statistically significant baseline clinical characteristics were assessed in a multivariate, competing‐risk regression model. VTE patients were matched to non‐VTE patients to determine the impact of VTE on overall survival. In all, 1762 patients were eligible for analysis. There were 144 (8.2%) and 90 (5.1%) events cumulative and within the first 6 months, respectively. VTE rates based on chemotherapy group demonstrated no statistical difference when gemcitabine/cisplatin was used as the comparator. Non‐urotheilal histology (SHR: 2.67; 95% CI: 1.72–4.16, P < 0.001), moderate to severe renal dysfunction (SHR: 2.12; 95% CI: 1.26–3.59, P = 0.005), and cardiovascular disease (CVD) or CVD risk factors (SHR: 2.27; 95% CI: 1.49–3.45, P = 0.001) were associated with increased VTE rates. Overall survival was worse in patients with VTE (median 6.0 m vs. 10.2 m, P < 0.001). Thus, in metastatic UC/VH patients, VTE is common and has a negative impact on survival. We identified multiple associated potential risk factors, although different chemotherapy regimens did not alter risk.

Chemotherapy regimen is associated with venous thromboembolism risk in patients with urothelial tract cancer

“…As previously demonstrated, history of VTE was strongly associated with development of a subsequent VTE . Additionally, renal dysfunction was associated with a 47% greater odds of developing a VTE, consistent with our findings in analyses of patients with locoregional and metastatic urothelial tract tumours using the Retrospective International Study of Cancers of the Urothelial Tract (RISC) database . Not surprisingly, the chemotherapy‐alone group had a statistically significantly higher VTE rate than the preoperative group, as the chemotherapy group probably represents patients with metastatic disease and thus higher tumour burden, which has been previously shown to be associated with more thrombotic events .…”

“…In addition, platinum‐based chemotherapy is a mainstay of treatment in bladder cancer in the peri‐operative and first‐line metastatic setting, further increasing a patient's thrombotic risk . Our group and others have previously shown that VTEs are frequent both in locoregional and metastatic urothelial tract tumours and that experiencing a VTE has clinical impact with shorter survival in the metastatic setting ; however, in our previous analyses we were not able to show statistically significant differences in VTE rates between the three most frequently utilized chemotherapy regimens: gemcitabine/cisplatin (GC); methotrexate/vinblastine/doxorubicin/cisplatin (MVAC) or similar regimens; and gemcitabine/carboplatin (CarboG). As there were numerical but not statistically significant differences between regimens, we hypothesize that our previous study may have lacked statistical power; therefore, we performed a retrospective cohort study using the larger Surveillance, Epidemiology and End Results (SEER) Medicare‐linked database to assess whether particular chemotherapy combinations had an impact on VTE rates in patients with urothelial tract cancer.…”

Thromboembolism in Patients with Bladder Cancer: Incidence, Risk Factors and Prevention

“…Both cisplatin and carboplatin-based regimens were associated with an increased VTE risk. An analysis of the Retrospective International Study of Cancers of the Urothelium (RISC), which included 1,762 patients with metastatic UC, of whom 1,337 received chemotherapy, showed a cumulative incidence of VTE of 9.6% and 3.2% among patients treated with and without chemotherapy, respectively [ 43 ]. On multivariate analysis, receipt of chemotherapy (but not type of chemotherapy regimen), pre-existing cardiovascular disease, moderate to severe renal dysfunction and variant histology were associated with an increased risk of VTE.…”

The Impact of Cisplatin- or Non-Cisplatin-Containing Chemotherapy on Long-Term and Conditional Survival of Patients with Advanced Urinary Tract Cancer

“…The Retrospective International Study of Cancers of the Urothelium (RISC) database represents the largest multinational database of patients with urinary tract cancer worldwide . It includes patients regardless of their participation in clinical trials, treated in the U.S., Europe, Israel, and Canada during the last decade.…”