title: 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.
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Jorge D
authors.initials: JD
authors.lastname: Ramos
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Martin F
authors.initials: MF
authors.lastname: Casey
authors.affiliation: University of Southampton, Southampton, England.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Crabb
authors.affiliation: National and Kapodistrian University of Athens, Athens, Greece.
authors.forename: Aristotelis
authors.initials: A
authors.lastname: Bamias
authors.affiliation: Dana Farber Cancer Institute, Boston, Massachusetts.
authors.forename: Lauren C
authors.initials: LC
authors.lastname: Harshman
authors.affiliation: Fox Chase Cancer Center, Philadelphia, Pennsylvania.
authors.forename: Yu-Ning
authors.initials: YN
authors.lastname: Wong
authors.affiliation: Hospital del Mar, Barcelona, Spain.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Ugo
authors.initials: U
authors.lastname: De Giorgi
authors.affiliation: Georges François Leclerc Center, Dijon, France.|Université de Bourgogne, Dijon, France.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Ladoire
authors.affiliation: Barts and the London School of Medicine, London, England.
authors.forename: Thomas
authors.initials: T
authors.lastname: Powles
authors.affiliation: City of Hope, Duarte, California.
authors.forename: Sumanta K
authors.initials: SK
authors.lastname: Pal
authors.affiliation: Heinrich-Heine-University, Düsseldorf, Germany.
authors.forename: Guenter
authors.initials: G
authors.lastname: Niegisch
authors.affiliation: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Meldola, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Recine
authors.affiliation: University of Michigan, Ann Arbor, Michigan.
authors.forename: Ajjai
authors.initials: A
authors.lastname: Alva
authors.affiliation: University of Utah, Salt Lake City, Utah.
authors.forename: Neeraj
authors.initials: N
authors.lastname: Agarwal
authors.affiliation: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Necchi
authors.affiliation: Karmanos Cancer Institute, Detroit, Michigan.
authors.forename: Ulka N
authors.initials: UN
authors.lastname: Vaishampayan
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, New York.
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Rosenberg
authors.affiliation: Icahn School of Medicine at Mount Sinai, New York, New York.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Galsky
authors.affiliation: University of Washington, Seattle, Washington.
authors.forename: Evan Y
authors.initials: EY
authors.lastname: Yu
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D002295:Carcinoma, Transitional Cell / Q000150:complications* / Q000188:drug therapy; D002945:Cisplatin / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011379:Prognosis; D012189:Retrospective Studies; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000150:complications* / Q000188:drug therapy; D054556:Venous Thromboembolism / Q000139:chemically induced / Q000453:epidemiology*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine
keywords: Urothelial; bladder cancer; chemotherapy survival; venous thromboembolism