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

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.

Cancer medicine. 2016 Dec 20 [Epub ahead of print]

Jorge D Ramos, Martin F Casey, Simon J Crabb, Aristotelis Bamias, Lauren C Harshman, Yu-Ning Wong, Joaquim Bellmunt, Ugo De Giorgi, Sylvain Ladoire, Thomas Powles, Sumanta K Pal, Guenter Niegisch, Federica Recine, Ajjai Alva, Neeraj Agarwal, Andrea Necchi, Ulka N Vaishampayan, Jonathan E Rosenberg, Matthew D Galsky, Evan Y Yu, RISC Investigators

University of Washington, Seattle, Washington., Icahn School of Medicine at Mount Sinai, New York, New York., University of Southampton, Southampton, England., National and Kapodistrian University of Athens, Athens, Greece., Dana Farber Cancer Institute, Boston, Massachusetts., Fox Chase Cancer Center, Philadelphia, Pennsylvania., Hospital del Mar, Barcelona, Spain., Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy., Georges François Leclerc Center, Dijon, France., Barts and the London School of Medicine, London, England., City of Hope, Duarte, California., Heinrich-Heine-University, Düsseldorf, Germany., University of Michigan, Ann Arbor, Michigan., University of Utah, Salt Lake City, Utah., Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy., Karmanos Cancer Institute, Detroit, Michigan., Memorial Sloan Kettering Cancer Center, New York, New York.