title: Neoadjuvant chemotherapy in small cell urothelial cancer improves pathologic downstaging and long-term outcomes: results from a retrospective study at the MD Anderson Cancer Center.
abstract: BACKGROUND
  Small cell urothelial carcinoma (SCUC) is a rare, aggressive malignancy with a propensity for early microscopic metastases. Data suggest that neoadjuvant chemotherapy may lead to improved survival compared with initial surgery.
  
  
  OBJECTIVE
  To determine the influence of neoadjuvant chemotherapy on survival of SCUC patients in a large single-institution cohort.
  
  
  METHODS
  Between 1985 and 2010, 172 patients were treated for SCUC at MD Anderson Cancer Center (MDACC). Clinical, pathologic, and surgical data were collected and analyzed.
  
  
  METHODS
  Overall survival (OS) and disease-specific survival (DSS) were calculated using the Kaplan-Meier method. Multivariable Cox proportional hazards models were used to evaluate the effects of neoadjuvant chemotherapy on survival.
  
  
  CONCLUSIONS
  Of 125 patients with resectable disease (≤ cT4aN0M0), 95 were surgical candidates. Forty-eight received neoadjuvant chemotherapy, and 47 underwent initial surgery. Neoadjuvant treatment was associated with improved OS and DSS compared with initial cystectomy (median OS: 159.5 mo vs 18.3 mo, p<0.001; 5-yr DSS: 79% vs 20%, p<0.001). Neoadjuvant chemotherapy resulted in pathologic downstaging to ≤ pT1N0 in 62% of tumors compared with only 9% treated with initial surgery (odds ratio: 44.55; 95% confidence interval, 10.39-191). Eight patients with clinically node-positive disease had surgical consolidation with cystectomy and extended lymph node dissection after clinical complete response to chemotherapy. Median OS and DSS in this group of patients were 23.3 mo and 21.8 mo, respectively, with 5-yr OS and DSS of 38%.
  
  
  CONCLUSIONS
  Neoadjuvant chemotherapy is associated with a high rate of pathologic downstaging and correlates with significantly higher survival compared with historical expectations. Although limited by a small sample size and retrospective analysis, in the context of a rare disease, this experience suggests neoadjuvant chemotherapy as a standard approach in treating SCUC.
authors.affiliation: Department of Cancer Medicine, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Siobhan P
authors.initials: SP
authors.lastname: Lynch
authors.forename: Yu
authors.initials: Y
authors.lastname: Shen
authors.forename: Ashish
authors.initials: A
authors.lastname: Kamat
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.forename: Jay B
authors.initials: JB
authors.lastname: Shah
authors.forename: Randall E
authors.initials: RE
authors.lastname: Millikan
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.forename: Arlene
authors.initials: A
authors.lastname: Siefker-Radtke
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D015653:Cystectomy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D016015:Logistic Models; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D016017:Odds Ratio; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013781:Texas; D013997:Time Factors; D016896:Treatment Outcome; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000187:drug effects* / Q000473:pathology