title: Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for histologically proven lymph node positive bladder cancer.
abstract: OBJECTIVE
  We gained insight into the effect of neoadjuvant chemotherapy and subsequent surgery in patients with bladder cancer with tumor positive lymph nodes.
  
  
  METHODS
  A total of 52 patients with histologically proven positive lymph nodes (by lymph node dissection or aspiration cytology) were treated with chemotherapy and post-chemotherapy surgery in case of partial or complete response. We evaluated response in the primary tumor and lymph nodes, long-term clinical outcome, and clinicopathological features potentially predictive of survival.
  
  
  RESULTS
  Complete response, partial response and stable/progressive disease were attained in 29%, 57% and 14%, and resulted in a 5-year survival of 42%, 19% and 0%, respectively. Objective response (HR 4.1), especially complete response (HR 8.0), was independently associated with survival. The prognostic values of lymph node status and bladder tumor status after methotrexate, vinblastine, doxorubicin and cisplatin were evaluated separately. A tumor negative bladder combined with tumor negative nodes were associated with improved survival (HR 4.4) as was a tumor negative lymph node region in the presence of residual bladder disease (HR 2.8). All patients with post-chemotherapy tumor positive nodes died within 2 years. In resected specimens residual disease was found in 4 of 15 clinically complete responders while no tumor could be detected in 3 of 29 clinically assessed as partial responders.
  
  
  CONCLUSIONS
  Response to chemotherapy is associated with improved survival, and our data suggest that lymph node status after methotrexate, vinblastine, doxorubicin and cisplatin is more important than local tumor status in this aspect. In the absence of reliable noninvasive methods, post-chemotherapy surgery in this series was the most adequate method of response evaluation and in limited partial responders led to long-term progression-free survival.
authors.affiliation: Departments of Urology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
authors.forename: J A
authors.initials: JA
authors.lastname: Nieuwenhuijzen
authors.forename: A
authors.initials: A
authors.lastname: Bex
authors.forename: W
authors.initials: W
authors.lastname: Meinhardt
authors.forename: J M
authors.initials: JM
authors.lastname: Kerst
authors.forename: J H
authors.initials: JH
authors.lastname: Schornagel
authors.forename: H
authors.initials: H
authors.lastname: VAN Tinteren
authors.forename: S
authors.initials: S
authors.lastname: Horenblas
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use*; D003663:Decision Trees; D004317:Doxorubicin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D014747:Vinblastine / Q000627:therapeutic use*
chemical_list: D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate