title: Lack of pathologic down-staging with neoadjuvant chemotherapy for muscle-invasive urothelial carcinoma of the bladder: a contemporary series.
abstract: BACKGROUND
  The postcystectomy survival benefit associated with the combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) neoadjuvant chemotherapy (NC) for muscle-invasive bladder cancer has been most evident in patients who achieve a pathologic complete response. The outcome of NC and open radical cystectomy (RC) was evaluated in a contemporary cohort of patients in a tertiary referral setting.
  
  
  METHODS
  From January 2006 to November 2007, 117 patients underwent open RC at Cleveland Clinic for muscle-invasive bladder cancer, 29 (25%) of whom received NC. Patient information was obtained from a prospective database.
  
  
  RESULTS
  Clinical stage at the time of diagnosis in the NC cohort was T2 in 23 (79%) and T3-4a in 6 (21%) patients. A total of 20 (69%) patients received the combination of gemcitabine and cisplatin (GC), 4 (14%) received MVAC, and 5 (17%) received other regimens. The median interval from the time of diagnosis of muscle-invasive bladder cancer to RC was 208 days (interquartile range, 149 days -327 days) in the NC cohort. Overall, only 2 patients (7%; 95% confidence interval [95% CI], 0 patients-17 patients) achieved a pathologic complete response, 18 (62%; 95% CI, 43 patients-81 patients) had nonorgan-confined residual cancer, and the overall median progression-free survival was 10.5 months (95% CI, 7 months -14 months).
  
  
  CONCLUSIONS
  Few RC patients in these investigators' recent experience achieved a pathologic complete response with NC, and most experienced rapid disease progression. These poor outcomes may be related to the use of non-MVAC-based regimens or excessive delay in performing RC. In the absence of supportive data for GC in the neoadjuvant setting, MVAC remained the preferred regimen. Excessive delays in performing RC may negate the benefit of NC.
authors.affiliation: Glickman Urologic and Kidney Institute, Cleveland Clinic, Cleveland, Ohio 44195-0001, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Weight
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Garcia
authors.forename: Donna E
authors.initials: DE
authors.lastname: Hansel
authors.forename: Amr F
authors.initials: AF
authors.lastname: Fergany
authors.forename: Steven C
authors.initials: SC
authors.lastname: Campbell
authors.forename: Michael C
authors.initials: MC
authors.lastname: Gong
authors.forename: J Stephen
authors.initials: JS
authors.lastname: Jones
authors.forename: Eric A
authors.initials: EA
authors.lastname: Klein
authors.forename: Robert
authors.initials: R
authors.lastname: Dreicer
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Stephenson
mesh_terms: D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000556:secondary; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D015331:Cohort Studies; D003131:Combined Modality Therapy; D015653:Cystectomy; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004317:Doxorubicin / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000188:drug therapy* / Q000556:secondary; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D012307:Risk Factors; D015996:Survival Rate; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology; D014747:Vinblastine / Q000627:therapeutic use; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D014747:Vinblastine; D004317:Doxorubicin; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine