title: Prognostic value of serum CA9 in patients with metastatic clear cell renal cell carcinoma under targeted therapy.
abstract: OBJECTIVE
  Carbonic anhydrase 9 (CA9) has been found to be one of most powerful biomarkers for clear-cell renal cell carcinoma (RCC). The serum CA9 is detectable. The aim of this study was to evaluate the potential prognostic role of serum CA9 in patients with metastatic clear-cell RCC patients under targeted therapy.
  
  
  METHODS
  Serum samples came from the randomized phase 2 TORAVA trial. All patients received a targeted therapy (arm A designed as experimental group: temsirolimus and bevacizumab combination; arm B: sunitinib; arm C: interferon-alfa and bevacizumab). Seventy cases of metastatic clear-cell RCC were analyzed. There were 49 males and 21 females. The age ranged from 33.5 to 79.1 years with a median of 61.2 years. Serum samples were collected before treatment. Serum CA9 was quantified by enzyme-linked immunosorbent assay (ELISA). The correlation of the serum CA9 levels with the clinical parameters, treatment response and overall survival was analyzed. Overall survival estimates were calculated using the Kaplan-Meier method and compared by the log-rank test.
  
  
  RESULTS
  Serum concentrations of CA9 ranged between 0 and 897.3 pg/ml, with an average of 94.4±176.6 pg/ml. There was no association between serum CA9 and clinical parameters such as Eastern Cooperative Oncology Group (ECOG) Performance Status (p=0.367) or Motzer classification (p=0.431). The serum CA9 levels were lower in the response group (64.7±104.7 pg/ml) than the no-response group (108.2±203.8 pg/ml), but the difference was not statisticlly significant (p=0.366). For the patient group overall, the Kaplan-Meier survival curve showed that high serum CA9 levels were significantly associated with shorter overall survival (hazard ratio=2.65, 95% confidence interval=1.19-5.92, log-rank test p=0.0136). For the major group of patients treated with temsirolimus and bevacizumab, the Kaplan-Meier survival curve showed that high serum CA9 levels were significantly associated with shorter overall survival (p=0.0006).
  
  
  CONCLUSIONS
  Serum CA9 levels may be of clinical interest to predict the outcome for patients under targeted therapy for metastatic clear-cell RCC. CA9 may be used to select patients with metastatic clear cell RCC for clinical trials.
authors.affiliation: Department of Urology and Kidney Transplantation, CHU La Réunion, 97405 Saint Denis cedex, La Réunion, France. marc.gigante@chu-reunion.fr
authors.forename: Marc
authors.initials: M
authors.lastname: Gigante
authors.forename: Guorong
authors.initials: G
authors.lastname: Li
authors.forename: Celine
authors.initials: C
authors.lastname: Ferlay
authors.forename: David
authors.initials: D
authors.lastname: Perol
authors.forename: Ellen
authors.initials: E
authors.lastname: Blanc
authors.forename: Stephane
authors.initials: S
authors.lastname: Paul
authors.forename: An
authors.initials: A
authors.lastname: Zhao
authors.forename: Jacques
authors.initials: J
authors.lastname: Tostain
authors.forename: Bernard
authors.initials: B
authors.lastname: Escudier
authors.forename: Sylvie
authors.initials: S
authors.lastname: Negrier
authors.forename: Christian
authors.initials: C
authors.lastname: Genin
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000951:Antigens, Neoplasm / Q000097:blood*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D016898:Interferon-alpha / Q000008:administration & dosage; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009362:Neoplasm Metastasis; D011758:Pyrroles / Q000627:therapeutic use*; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D007211:Indoles; D016898:Interferon-alpha; D011758:Pyrroles; D000068258:Bevacizumab; C401859:temsirolimus; C089226:CA9 protein, human; D000071231:Carbonic Anhydrase IX; D002256:Carbonic Anhydrases; D000077210:Sunitinib; D020123:Sirolimus