title: Neoadjuvant CMV chemotherapy plus radical cystectomy in locally advanced bladder cancer: the impact of pathologic response on long-term results.
abstract: OBJECTIVE
  Neoadjuvant systemic chemotherapy in infiltrating transitional cell carcinoma of the bladder has proved to be effective and to provide a pathologic complete response in about 30% of patients. No survival benefit has yet been proved.
  
  
  METHODS
  We analyzed the outcome of 75 patients with advanced bladder cancer (stages T2-T4 N+/N0 M0) treated from 1985 to 1993 at two institutions in the same geographic area with 2 or 3 cycles of neoadjuvant CMV (cisplatin, methotrexate and vinblastine) chemotherapy plus cystectomy. Transurethral resection of the tumor was expressly avoided in order to keep the tumor intact as a marker lesion to evaluate response to chemotherapy.
  
  
  RESULTS
  At the time of analysis, the median follow-up of 67 assessable patients was 51.5 +/- 3.9 (SE) months. Forty-six patients (69%) had clinical evidence of extravesical spread of the bladder tumor and 6 of lymph node metastases at presentation. After cystectomy, a pathologic complete response (pT0, pN0) was achieved in only 6 cases (9%) and a pathologic partial response in 32 patients (48%). The overall 5-year survival rate of all patients was 61 +/- 6%. Those patients who had a major response to chemotherapy (pCR +pPR) had a 5-year disease-free survival rate of 74%, which was statistically higher (P = 0.0021) than the 44% for the remaining nonresponding patients (pNR). Overall, 43% of the patients with stage T2-T3a disease achieved tumor downstaging (CR, 5%; PR, 38%) compared with 63% of the patients with T3b-T4 (CR, 11%; PR, 52%), although there was no significant difference in 5-year survival curves between the two groups.
  
  
  CONCLUSIONS
  A pathologic complete response was achieved in less than 10% of the cases without a preoperative tumor resection. Unfortunately, most of the responses were only partial. Even though the study appears to suggest a survival advantage for those patients who achieved a downstaging, CMV chemotherapy had a limited curative potential in most of the patients. It seems unlikely that determinant proof will be obtained that neoadjuvant chemotherapy may improve survival over a nontreatment control arm. The intrinsic chemoresistance or the suboptimal response to chemotherapy of bladder cancer remains the most adverse prognostic factor.
authors.affiliation: Department of Urology, Scientific Institute Ospedale San Raffaele, Milan, Italy.
authors.forename: V
authors.initials: V
authors.lastname: Scattoni
authors.forename: A
authors.initials: A
authors.lastname: Bolognesi
authors.forename: C
authors.initials: C
authors.lastname: Cozzarini
authors.forename: F
authors.initials: F
authors.lastname: Francesca
authors.forename: M
authors.initials: M
authors.lastname: Grasso
authors.forename: L
authors.initials: L
authors.lastname: Galli
authors.forename: T
authors.initials: T
authors.lastname: Torelli
authors.forename: B
authors.initials: B
authors.lastname: Campo
authors.forename: E
authors.initials: E
authors.lastname: Villa
authors.forename: P
authors.initials: P
authors.lastname: Rigatti
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D015653:Cystectomy / Q000379:methods; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D006801:Humans; D008727:Methotrexate / Q000008:administration & dosage; D009367:Neoplasm Staging; D011379:Prognosis; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D014747:Vinblastine / Q000008:administration & dosage
chemical_list: D014747:Vinblastine; D002945:Cisplatin; D008727:Methotrexate