title: Impact of preoperative anemia on oncologic outcomes of upper tract urothelial carcinoma treated with radical nephroureterectomy.
abstract: OBJECTIVE
  We evaluated the impact of preoperative anemia on oncologic outcomes in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy.
  
  
  METHODS
  A total of 282 patients with upper tract urothelial carcinoma underwent radical nephroureterectomy. Preoperatively measured hemoglobin values were stratified into normal and anemia based on the WHO classification of 13 gm/dl or less and 12 or less considered anemia in males and females, respectively. We performed sensitivity analysis based on contemporary anemia classifications adjusted for the impact of age, gender and race with anemia considered a hemoglobin value of 13.7 gm/dl or less and 13.2 or less in white males younger than 60 and 60 years old or older, respectively, and 12.2 gm/dl or less in white females of all ages. Univariable and multivariable Cox regression analyses were done to assess the effects of anemia on oncologic outcomes.
  
  
  RESULTS
  Median preoperative hemoglobin was 13.2 gm/dl (IQR 11.7, 14.3). A total of 112 patients (39.7%) were anemic by the WHO classification vs 129 (45.7%) by the contemporary classification. Anemia was associated with lymph node metastasis, lymphovascular invasion, sessile tumor architecture, tumor necrosis, advanced age and a higher ECOG (Eastern Cooperative Oncology Group) performance score using the WHO and/or the contemporary definition (p ≤0.044). At a median 30-month followup anemia was associated with decreased recurrence-free (p ≤0.008) and cancer specific (p <0.001) survival on Kaplan-Meier analyses. On multivariable analysis adjusted for standard clinicopathological factors anemia remained an independent predictor of disease recurrence (HR 1.76, 95% CI 1.17-2.63 and 1.89, 95% CI 1.26-2.86) and cancer specific mortality (HR 1.88, 95% CI 1.15-3.08 and 2.04, 95% CI 1.21-3.45) by the WHO and contemporary classifications, respectively.
  
  
  CONCLUSIONS
  Preoperative anemia is an independent predictor of disease recurrence and cancer specific mortality. It is associated with aggressive tumor features in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. Hemoglobin is a promising marker for patient counseling and risk stratification for additional treatment decision making.
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: mrink@uke.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Nasim
authors.initials: N
authors.lastname: Sharifi
authors.affiliation: Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany.
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.affiliation: Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Regensburg, Germany.
authors.forename: Atiqullah
authors.initials: A
authors.lastname: Aziz
authors.affiliation: Department of Urology, University of Tübingen, Tübingen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Miller
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Kluth
authors.affiliation: Department of Urology, University of Tübingen, Tübingen, Germany.
authors.forename: Theofanis
authors.initials: T
authors.lastname: Ngamsri
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Roland
authors.initials: R
authors.lastname: Dahlem
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Felix K
authors.initials: FK
authors.lastname: Chun
authors.affiliation: Department of Urology, Medical University Vienna, Vienna, Austria.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, University of Tübingen, Tübingen, Germany.
authors.forename: Arnulf
authors.initials: A
authors.lastname: Stenzl
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Margit
authors.initials: M
authors.lastname: Fisch
authors.affiliation: Department of Urology, University of Tübingen, Tübingen, Germany.
authors.forename: Georgios
authors.initials: G
authors.lastname: Gakis
mesh_terms: D000368:Aged; D000740:Anemia / Q000628:therapy*; D016063:Blood Loss, Surgical / Q000706:statistics & numerical data; D015897:Comorbidity; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D057234:Preoperative Period; D012008:Recurrence; D012189:Retrospective Studies; D014513:Ureter / Q000601:surgery*; D014571:Urologic Neoplasms / Q000453:epidemiology / Q000401:mortality / Q000601:surgery*; D013520:Urologic Surgical Procedures / Q000379:methods*; D019459:Urothelium / Q000473:pathology
keywords: CT; LVI; RNU; UCB; URS; UTUC; anemia; bladder urothelial carcinoma; carcinoma; computerized tomography; hemoglobins; kidney; lymphovascular invasion; radical nephroureterectomy; upper tract urothelial carcinoma; ureter; ureterorenoscopy