title: Prognostic serum markers in patients with high-grade upper tract urothelial carcinoma.
abstract: The role of preoperative serum-based markers in predicting survival outcomes of patients has been reported for several cancer types; however, their association with upper tract urothelial carcinoma (UTUC) prognosis is unclear. We evaluated the role of systemic serum-based markers in predicting adverse pathological features and survival outcomes in patients surgically treated for high-grade (HG) UTUC.
  
  
  
  We retrospectively reviewed all patients undergoing surgery for HG UTUC between June 2006 and July 2013 at our institution. Comprehensive clinicopathologic data and preoperative serum-based markers including hemoglobin, white blood cell count, platelet count, serum albumin, calcium, and liver function tests were recorded. Associations of serum markers with pathologic features and recurrence-free survival (RFS) were determined by logistic and Cox regression analyses, respectively. The concordance index for the oncologic outcomes model was determined.
  
  
  
  In total, 101 patients were identified with a median follow-up of 18.5 months (range: 1-74mo). In all, 60% of patients had pT2 or less and 11% had nodal metastases. Preoperative elevated alkaline phosphatase (ALP) (≥116IU/l) was associated with multiple adverse pathologic features including advanced T stage, lymphovascular invasion, and histologic necrosis. On univariate analysis, serum markers independently associated with RFS included hemoglobin≤12.9 (hazards ratio [HR] = 2.51; 95% CI: 1.17-5.36, P = 0.018), albumin≤4g/dl (HR = 4.4; 95% CI: 2.04-9.30; P<0.0001), ALP≥116U/l (HR = 13.3; 95% CI: 5.3-33.52, P<0.0001), alanine transaminase≥27 (HR = 2.63, 95% CI: 1.11-6.21, P = 0.028), serum aspartate transaminase≥20 (HR = 2.21, 95% CI: 1.04-4.69, P = 0.038), and corrected calcium≥9.3 (HR = 2.45, 95% CI: 1.01-5.93, P = 0.047). The 2 strongest predictors, albumin and ALP, were combined to form an AA score (range: 0-2), which improved the baseline preoperative clinical model concordance index for prediction of RFS from 0.626 to 0.799.
  
  
  
  In HG UTUC, elevated preoperative ALP was associated with adverse pathologic features. Additionally, elevated ALP and low albumin were independently associated with worse RFS and overall survival. These serum-based markers are often measured in the preoperative workup of UTUC, and thus they can be included in future prognostic models to risk stratify patients.
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Kunj R
authors.initials: KR
authors.lastname: Sheth
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Ahmed Q
authors.initials: AQ
authors.lastname: Haddad
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Omotola S
authors.initials: OS
authors.lastname: Ashorobi
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Meissner
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, The University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: vitaly.margulis@utsouthwestern.edu.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D014571:Urologic Neoplasms / Q000097:blood* / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D000469:Alkaline Phosphatase
keywords: Inflammatory markers; Recurrence-free survival; Upper tract urothelial carcinoma