title: Pretherapeutic gamma-glutamyltransferase is an independent prognostic factor for patients with renal cell carcinoma.
abstract: BACKGROUND
  Gamma-glutamyltransferase (GGT) regulates apoptotic balance and promotes cancer progression and invasion. Higher pretherapeutic GGT serum levels have been associated with worse outcomes in various malignancies, but there are no data for renal cell carcinoma (RCC).
  
  
  METHODS
  Pretherapeutic GGT serum levels and clinicopathological parameters were retrospectively evaluated in 921 consecutive RCC patients treated with nephrectomy at a single institution between 1998 and 2013. Gamma-glutamyltransferase was analysed as continuous and categorical variable. Associations with RCC-specific survival were assessed with Cox proportional hazards models. Discrimination was measured with the C-index. Decision-curve analysis was used to evaluate the clinical net benefit. The median postoperative follow-up was 45 months.
  
  
  RESULTS
  Median pretherapeutic serum GGT level was 25 U l(-1). Gamma-glutamyltransferase levels increased with advancing T (P<0.001), N (P=0.006) and M stages (P<0.001), higher grades (P<0.001), and presence of tumour necrosis (P<0.001). An increase of GGT by 10 U l(-1) was associated with an increase in the risk of death from RCC by 4% (HR 1.04, P<0.001). Based on recursive partitioning-based survival tree analysis, we defined four prognostic categories of GGT: normal low (<17.5 U l(-1)), normal high (17.5 to <34.5 U l(-1)), elevated (34.5 to <181.5 U l(-1)), and highly elevated (⩾181.5 U l(-1)). In multivariable analyses that adjusted for the effect of standard features, both continuously and categorically coded GGT were independent prognostic factors. Adding GGT to a model that included standard features increased the discrimination by 0.9% to 1.8% and improved the clinical net benefit.
  
  
  CONCLUSIONS
  Pretherapeutic serum GGT is a novel and independent prognostic factor for patients with RCC. Stratifying patients into prognostic subgroups according to GGT may be used for patient counselling, tailoring surveillance, individualised treatment planning, and clinical trial design.
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: S L
authors.initials: SL
authors.lastname: Hofbauer
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: K I
authors.initials: KI
authors.lastname: Stangl
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: de Martino
authors.affiliation: 1] Department of Urology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria [2] Department of Urology, Centre hospitalier universitaire vaudois, Rue du Bugnon 46, 1011 Lausanne, Switzerland.
authors.forename: I
authors.initials: I
authors.lastname: Lucca
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: A
authors.initials: A
authors.lastname: Haitel
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: S F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna and General Hospital, Währinger Gürtel 18-20, 1090 Vienna, Austria.
authors.forename: T
authors.initials: T
authors.lastname: Klatte
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D005723:gamma-Glutamyltransferase