title: A systematic review and meta-analysis of adjuvant and neoadjuvant chemotherapy for upper tract urothelial carcinoma.
abstract: BACKGROUND
  The role of adjuvant chemotherapy (AC) or neoadjuvant chemotherapy (NC) remains poorly defined for the management of upper tract urothelial carcinoma (UTUC), although some studies suggest a benefit.
  
  
  OBJECTIVE
  To update the current evidence on the role of NC and AC for UTUC patients.
  
  
  METHODS
  We searched for all studies investigating NC or AC for UTUC in Medline, Embase, the Cochrane Central Register of Controlled Trials, and abstracts from the American Society of Clinical Oncology meetings prior to February 2014. A systematic review and meta-analysis were performed.
  
  
  RESULTS
  No randomized trials investigated the role of AC for UTUC. There was one prospective study (n=36) investigating adjuvant carboplatin-paclitaxel and nine retrospective studies, with a total of 482 patients receiving cisplatin-based or non-cisplatin-based AC after nephroureterectomy (NU) and 1300 patients receiving NU alone. Across three cisplatin-based studies, the pooled hazard ratio (HR) for overall survival (OS) was 0.43 (95% confidence interval [CI], 0.21-0.89; p=0.023) compared with those who received surgery alone. For disease-free survival (DFS), the pooled HR across two studies was 0.49 (95% CI, 0.24-0.99; p=0.048). Benefit was not seen for non-cisplatin-based regimens. For NC, two phase 2 trials demonstrated favorable pathologic downstaging rates, with 3-yr OS and disease-specific survival (DSS) ≤ 93%. Across two retrospective studies investigating NC, there was a DSS benefit, with a pooled HR of 0.41 (95% CI, 0.22-0.76; p=0.005).
  
  
  CONCLUSIONS
  There appears to be an OS and DFS benefit for cisplatin-based AC in UTUC. This evidence is limited by the retrospective nature of studies and their relatively small sample size. NC appears to be promising, but more trials are needed to confirm its utility.
  
  
  RESULTS
  After a comprehensive search of studies examining the role of chemotherapy for upper tract urothelial cancer, the pooled evidence shows that cisplatin-based adjuvant chemotherapy was beneficial for prolonging survival.
authors.affiliation: Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA; Division of Urology and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Leow
authors.affiliation: University of Massachusetts Medical School, Worcester, MA, USA.
authors.forename: William
authors.initials: W
authors.lastname: Martin-Doyle
authors.affiliation: Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: André P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA; Division of Urology and Center for Surgery and Public Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Steven L
authors.initials: SL
authors.lastname: Chang
authors.affiliation: Bladder Cancer Center, Dana-Farber/Brigham and Women's Cancer Center, Harvard Medical School, Boston, MA, USA. Electronic address: joaquim_bellmunt@dfci.harvard.edu.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002277:Carcinoma / Q000188:drug therapy* / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000601:surgery; D020360:Neoadjuvant Therapy; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate; D014516:Ureteral Neoplasms / Q000188:drug therapy* / Q000601:surgery; D019459:Urothelium
chemical_list: D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin
keywords: Adjuvant; Chemotherapy; Kidney neoplasms; Neoadjuvant; Nephroureterectomy; Renal pelvic tumors; Upper tract urothelial carcinoma; Ureteral neoplasms; Urothelial carcinoma