title: High rates of advanced disease, complications, and decline of renal function after radical nephroureterectomy.
abstract: OBJECTIVE
  Recurrences remain common following radical nephroureterectomy (RNU) for locally advanced upper-tract urothelial carcinoma (UTUC). We review a cohort of RNU patients to identify the incidence of locally advanced disease, decline in renal function, complications, and utilization of adjuvant chemotherapy (AC).
  
  
  METHODS
  Institutional databases from 7 academic medical centers identified 414 RNU patients treated between 2003 and 2012 who had not received neoadjuvant chemotherapy. Glomerular filtration rate was estimated using the Modification of Diet in Renal Disease equation. Complications were classified according to the modified Clavien system. Cox proportional hazard modeling and Kaplan-Meier analysis determined factors associated with cancer-specific survival.
  
  
  RESULTS
  Of 414 patients, 177 (43%) had locally advanced disease, including 118 pT3N0/Nx, 13 pT4N0/Nx, and 46 pTanyN+. Estimated 3- and 5-year cancer-specific survival was 47% and 34%, respectively. Only 31% of patients with locally advanced UTUC received AC. Mean estimated glomerular filtration rate declined from 59 to 51 ml/min/1.73 m(2) following RNU, including a new-onset decline below 60 and 45 ml/min/1.73 m(2) in 25% and 15% of patients, respectively (P<0.001 for both). Complications occurred in 46 of 177 (26%) patients, of which one-quarter were grade III or IV. Increasing age (Hazard Ratio (HR) 1.4, P = 0.03), positive surgical margins (HR 2.1, P = 0.01), and positive lymph nodes (HR 4.3, P<0.001) were associated with an increased risk of death from UTUC, whereas receipt of AC (HR 0.85, P = 0.05) was associated with a decrease in UTUC mortality.
  
  
  CONCLUSIONS
  Under one-third of RNU patients with locally advanced UTUC cancers received AC. Perioperative complications and decline in renal function may have contributed to this low rate. Such data further underscore the need for continued discussion regarding the use of chemotherapy in a neoadjuvant setting for appropriately selected patients with UTUC.
authors.affiliation: Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA. Electronic address: jraman@hmc.psu.edu.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Yu-Kuan
authors.initials: YK
authors.lastname: Lin
authors.affiliation: Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Kaag
authors.affiliation: Division of Urology, University of Kentucky Medical Center, Lexington, KY.
authors.forename: Timothy
authors.initials: T
authors.lastname: Atkinson
authors.affiliation: Division of Urology, University of Kentucky Medical Center, Lexington, KY.
authors.forename: Paul
authors.initials: P
authors.lastname: Crispen
authors.affiliation: Division of Urology, Stroger Cook County Hospitals, Chicago, IL.
authors.forename: Mark
authors.initials: M
authors.lastname: Wille
authors.affiliation: Section of Urology, University of Chicago Medical Center, Chicago, IL.
authors.forename: Norm
authors.initials: N
authors.lastname: Smith
authors.affiliation: Department of Urology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Mark
authors.initials: M
authors.lastname: Hockenberry
authors.affiliation: Department of Urology, University of Pennsylvania, Philadelphia, PA.
authors.forename: Thomas
authors.initials: T
authors.lastname: Guzzo
authors.affiliation: Department of Urology, University of Rennes, Rennes, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Peyronnet
authors.affiliation: Department of Urology, University of Rennes, Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.affiliation: Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Jay
authors.initials: J
authors.lastname: Simhan
authors.affiliation: Division of Urologic Oncology, Fox Chase Cancer Center, Philadelphia, PA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kutikov
authors.affiliation: Department of Urology, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.
authors.forename: Eugene
authors.initials: E
authors.lastname: Cha
authors.affiliation: Department of Urology, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.
authors.forename: Michael
authors.initials: M
authors.lastname: Herman
authors.affiliation: Department of Urology, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.
authors.forename: Douglas
authors.initials: D
authors.lastname: Scherr
authors.affiliation: Department of Urology, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY; Division of Medical Oncology, New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Urology, Mayo Clinic, Rochester, MN.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Boorjian
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000503:physiopathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate; D006801:Humans; D053208:Kaplan-Meier Estimate; D007677:Kidney Function Tests; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009392:Nephrectomy / Q000009:adverse effects / Q000379:methods*; D017063:Outcome Assessment, Health Care / Q000379:methods / Q000706:statistics & numerical data; D011183:Postoperative Complications; D016016:Proportional Hazards Models; D012307:Risk Factors; D014513:Ureter / Q000601:surgery*; D014571:Urologic Neoplasms / Q000503:physiopathology / Q000601:surgery*
keywords: Clavien complications; Locally advanced disease; Perioperative chemotherapy; Renal-function changes; Urothelial carcinoma