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.

Keywords: Urothelial; bladder cancer; chemotherapy survival; venous thromboembolism.

Figure 1

Flowchart of patient inclusion and exclusion criteria.

Figure 2

Absolute cumulative incidence of venous thromboembolic events based on first‐line chemotherapy regimen. CTX, chemotherapy; VTE, venous thromboembolism. *Carboplatin and oxaliplatin regimens (excluding gemcitabine and carboplatin) not shown due to comparatively smaller sample size, representing 4.3% of the cohort.

Figure 3

Kaplan–Meier survival curve of patients who had a venous thromboembolic event (VTE) and no venous thromboembolic event (no VTE). P‐value is a result of the log‐rank test. OS, overall survival (in months).