title: Radical nephroureterectomy for pathologic T4 upper tract urothelial cancer: can oncologic outcomes be improved with multimodality therapy?
abstract: OBJECTIVE
  To report the outcomes of patients with pathologic T4 UTUC and investigate the potential impact of peri-operative chemotherapy combined with radical nephroureterectomy (RNU) and regional lymph node dissection (LND) on oncologic outcomes.
  
  
  METHODS
  Patients with pathologic T4 UTUC were identified from the cohort of 1464 patients treated with RNU at 13 academic centers between 1987 and 2007. Oncologic outcomes were stratified according to utilization of perioperative systemic chemotherapy and regional LND as an adjunct to RNU.
  
  
  RESULTS
  The study included 69 patients, 42 males (61%) with median age 73 (range 43-98). Median follow-up was 17 months (range: 6-88). Lymphovascular invasion was found in 47 (68%) and regional lymph node metastases were found in 31 (45%). Peri-operative chemotherapy was utilized in 29 (42%) patients. Patients treated with peri-operative chemotherapy and RNU with LND demonstrated superior oncologic outcomes compared to those not treated by chemotherapy and/or LND during RNU (3Y-DFS: 35% vs. 10%; P = 0.02 and 3Y-CSS: 28% vs. 14%; P = 0.08). In multivariate Cox regression analysis, administration of peri-operative chemotherapy and utilization of LND during RNU was associated with lower probability of recurrence (HR: 0.4, P = 0.01), and cancer specific mortality (HR: 0.5, P = 0.06).
  
  
  CONCLUSIONS
  Pathological T4 UTUC is associated with poor prognosis. Peri-operative chemotherapy combined with aggressive surgery, including lymph node dissection, may improve oncological outcomes. Our findings support the use of aggressive multimodal treatment in patients with advanced UTUC.
authors.affiliation: UT Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Ramy F
authors.initials: RF
authors.lastname: Youssef
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.forename: Richard
authors.initials: R
authors.lastname: Zigeuner
authors.forename: Marco
authors.initials: M
authors.lastname: Roscigno
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.forename: Wassim
authors.initials: W
authors.lastname: Kassouf
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008197:Lymph Node Excision; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods*; D012044:Regression Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014513:Ureter / Q000601:surgery*; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery*
chemical_list: D000970:Antineoplastic Agents