title: Significance of lymphovascular invasion in organ-confined, node-negative urothelial cancer of the bladder: data from the prospective p53-MVAC trial.
abstract: OBJECTIVE
  To investigate the association between lymphovascular invasion (LVI) and clinical outcome in organ-confined, node-negative urothelial cancer of the bladder (UCB) in a post hoc analysis of a prospective clinical trial. To explore the effect of adjuvant chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) on outcome in the subset of patients whose tumours exhibited LVI.
  
  
  METHODS
  Surgical and tumour factors were extracted from the operative and pathology reports of 499 patients who had undergone radical cystectomy (RC) for pT1-T2 N0 UCB in the p53-MVAC trial (Southwest Oncology Group 4B951/NCT00005047). The presence or absence of LVI was determined by pathological examination of transurethral resection or RC specimens. Variables were examined in univariate and multivariate Cox proportional hazards models for associations with time to recurrence (TTR) and overall survival (OS).
  
  
  RESULTS
  Among 499 patients with a median follow-up of 4.9 years, a subset of 102 (20%) had LVI-positive tumours. Of these, 34 patients had pT1 and 68 had pT2 disease. LVI was significantly associated with TTR with a hazard ratio (HR) of 1.78 [95% confidence interval (CI) 1.15-2.77; number of events (EV) 95; P = 0.01) and with OS with a HR of 2.02 (95% CI 1.31-3.11; EV 98; P = 0.001) after adjustment for pathological stage. Among 27 patients with LVI-positive tumours who were randomised to receive adjuvant chemotherapy, receiving MVAC was not significantly associated with TTR (HR 0.70, 95% CI 0.16-3.17; EV 7; P = 0.65) or with OS (HR 0.45, 95% CI 0.11-1.83; EV 9; P = 0.26).
  
  
  CONCLUSIONS
  Our post hoc analysis of the p53-MVAC trial revealed an association between LVI and shorter TTR and OS in patients with pT1-T2N0 disease. The analysis did not show a statistically significant benefit of adjuvant MVAC chemotherapy in patients with LVI, although a possible benefit was not excluded.
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Friedrich-Carl
authors.initials: FC
authors.lastname: von Rundstedt
authors.affiliation: Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Mata
authors.affiliation: USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
authors.forename: Susan
authors.initials: S
authors.lastname: Groshen
authors.affiliation: Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Stein
authors.affiliation: Aresty Department of Urology, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: Skinner
authors.affiliation: Section of Hematology/Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.
authors.forename: Walter M
authors.initials: WM
authors.lastname: Stadler
authors.affiliation: Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA.|Department of Biochemistry and Molecular Biology, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Cote
authors.affiliation: Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL, USA.|Department of Urology, Miller School of Medicine, University of Miami, Miami, FL, USA.
authors.forename: Oleksandr N
authors.initials: ON
authors.lastname: Kryvenko
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Guilherme
authors.initials: G
authors.lastname: Godoy
authors.affiliation: Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D011446:Prospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019459:Urothelium / Q000473:pathology; D014747:Vinblastine / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate
keywords: SWOG; adjuvant chemotherapy; lymphovascular invasion; urothelial cancer