title: The effect of cystectomy, and perioperative methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy on the risk and pattern of relapse in patients with muscle invasive bladder cancer.
abstract: OBJECTIVE
  Trials have demonstrated decreased relapse with perioperative methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) chemotherapy in patients with muscle invasive bladder cancer. We evaluated whether the benefit of chemotherapy correlates with its effects on distant or pelvic relapse.
  
  
  METHODS
  We retrospectively evaluated the records of all 107 patients who underwent cystectomy for muscle invasive bladder cancer at our institution between 1988 and 1994. Factors predicting relapse were identified and used to group patients at high or low risk. The outcome in each group with and without M-VAC chemotherapy was then analyzed in terms of overall, metastatic and pelvic relapse. Univariate analysis was performed using the Kaplan-Meier method and log rank statistic, and multivariate analysis was done using the Cox proportional hazards model. Median survival was 29 months for patients free of disease.
  
  
  RESULTS
  Pathological stage T3 or greater according to the American Joint Committee on Cancer, tumor greater than 3 cm. and creatinine greater than 1.5-fold normal were independent poor prognostic factors in patients treated with cystectomy only. Patients with any of these factors or metastatic involvement of the pelvic lymph nodes were considered at high risk. All 35 low risk patients were treated with cystectomy only and had an excellent outcome with a 3-year relapse-free survival plus or minus standard error of 93% +/- 5%. The 3-year rates in 52 and 20 high risk patients treated without and with chemotherapy, respectively, were 42% +/- 8% versus 57% +/- 13% for relapse-free survival (p = 0.17), 38% +/- 9% versus 8% +/- 8% for pelvic failure (p = 0.02) and 39% +/- 9% versus 38% +/- 13% for distant metastases (not significant). Multivariate analysis of patients who underwent pelvic lymphadenectomy revealed that perioperative chemotherapy improved relapse-free survival and pelvic control but not metastatic control (p = 0.03, 0.02 and 0.31, respectively).
  
  
  CONCLUSIONS
  Low risk patients have excellent disease control when treated with cystectomy only. Those with high risk features are at substantial risk for pelvic failure (38% at 3 years) after cystectomy only. Perioperative M-VAC chemotherapy has a profound impact on pelvic but not on metastatic failure.
authors.affiliation: Department of Radiation Oncology, College of Physicians and Surgeons, School of Public Health, Columbia University, New York, New York, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Ennis
authors.forename: D P
authors.initials: DP
authors.lastname: Petrylak
authors.forename: P
authors.initials: P
authors.lastname: Singh
authors.forename: E
authors.initials: E
authors.lastname: Bagiella
authors.forename: K M
authors.initials: KM
authors.lastname: O'Toole
authors.forename: M C
authors.initials: MC
authors.lastname: Benson
authors.forename: C A
authors.initials: CA
authors.lastname: Olsson
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015653:Cystectomy; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D009130:Muscle, Smooth; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D009367:Neoplasm Staging; D012189:Retrospective Studies; D012307:Risk Factors; D017211:Treatment Failure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D014747:Vinblastine / Q000627:therapeutic use
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate