title: Bladder preservation therapy for muscle-invading bladder cancers on Radiation Therapy Oncology Group trials 8802, 8903, 9506, and 9706: vascular endothelial growth factor B overexpression predicts for increased distant metastasis and shorter survival.
abstract: BACKGROUND
  From 1988 to 1999, the Radiation Therapy Oncology Group (RTOG) conducted four prospective studies (8802, 8903, 9506, 9706) of patients with clinical stage T2-4a muscle-invasive bladder cancer. Treatment was selective bladder preservation using transurethral surgery (TURBT) plus cisplatin-based induction and consolidation chemoradiation regimens, reserving radical cystectomy for invasive tumor recurrence. We investigated vascular endothelial growth factor (VEGF) pathway biomarkers in this unique clinical dataset (median follow-up of 3.1 years).
  
  
  METHODS
  A total of 43 patients with tissue available from the entry TURBT were included in this analysis. Expression of VEGF ligands and receptors were quantified and scored by the AQUA platform (HistoRX, now Genoptix, Carlsbad, CA) and analyzed after median split.
  
  
  RESULTS
  VEGF expression levels were not associated with increased rates of complete response to induction chemoradiation. Higher levels of cytoplasmic VEGF-B, VEGF-C, and VEGF-R2 were associated with decreased overall survival rates. The 3-year overall survival estimates for high and low expressers were 43.7% and 75% for VEGF-B cytoplasm (p = .01), 40.2% and 86.7% for VEGF-C cytoplasm (p = .01), and 49.7% and 66.7% for VEGF-R2 cytoplasm (p = .02). Higher expression levels of cytoplasm VEGF-B were associated with higher rates of distant failure (p = .01).
  
  
  CONCLUSIONS
  Although VEGF ligands and receptors do not appear to be associated with complete response to induction chemoradiation for muscle-invasive bladder cancer, we report significant associations with overall survival and distant failure for certain VEGF family members.
authors.affiliation: Department of Radiation Oncology, Wexner Medical Center, Ohio State University, Columbus, Ohio 43210, USA. TL@osumc.edu
authors.forename: Tim
authors.initials: T
authors.lastname: Lautenschlaeger
authors.forename: Asha
authors.initials: A
authors.lastname: George
authors.forename: Alexander C
authors.initials: AC
authors.lastname: Klimowicz
authors.forename: Jason A
authors.initials: JA
authors.lastname: Efstathiou
authors.forename: Chin-Lee
authors.initials: CL
authors.lastname: Wu
authors.forename: Howard
authors.initials: H
authors.lastname: Sandler
authors.forename: William U
authors.initials: WU
authors.lastname: Shipley
authors.forename: William J
authors.initials: WJ
authors.lastname: Tester
authors.forename: Michael P
authors.initials: MP
authors.lastname: Hagan
authors.forename: Anthony M
authors.initials: AM
authors.lastname: Magliocco
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
mesh_terms: D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009132:Muscles / Q000473:pathology / Q000601:surgery; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D015996:Survival Rate; D001743:Urinary Bladder / Q000473:pathology* / Q000601:surgery; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D042561:Vascular Endothelial Growth Factor B / Q000096:biosynthesis / Q000235:genetics*; D042582:Vascular Endothelial Growth Factor C / Q000096:biosynthesis / Q000235:genetics
chemical_list: C467485:VEGFB protein, human; D042561:Vascular Endothelial Growth Factor B; D042582:Vascular Endothelial Growth Factor C; D002945:Cisplatin