title: Concomitant carcinoma in situ is a feature of aggressive disease in patients with organ confined urothelial carcinoma following radical nephroureterectomy.
abstract: OBJECTIVE
  Carcinoma in situ (CIS) is associated with increased risk of progression when found with high-grade non-muscle-invasive bladder cancer, yet its impact is less clear in the upper urinary tract. In the current study, we evaluated the impact of concomitant CIS on recurrence-free survival and cancer-specific survival following radical nephroureterectomy for upper tract urothelial carcinoma (UTUC).
  
  
  METHODS
  A multi-institutional retrospective cohort of 1,387 patients undergoing radical nephroureterectomy was identified. Concomitant CIS was defined as the presence of CIS in association with another pathologic stage; patients with CIS alone were excluded from the analysis. The presence of concomitant CIS served as the exposure variable with disease recurrence and cancer-specific mortality as the outcomes. Organ-confined disease was defined as AJCC/UICC stage II or lower.
  
  
  RESULTS
  Concomitant CIS was identified in 371 of 1,387 (26.7%) patients and was significantly more common in patients with a previous bladder cancer history, high grade, and high stage tumors. In a multivariable analysis, concomitant CIS was a predictor of disease recurrence (HR = 1.25, P = 0.04) and cancer specific mortality (HR = 1.34, P = 0.05) for patients with organ-confined UTUC, but not in the entire cohort. Other prognostic variables, such as grade, stage, lymphovascular invasion, and lymph node status, were associated with poorer overall and recurrence-free survival for all patients.
  
  
  CONCLUSIONS
  The presence of concomitant CIS in patients with organ-confined UTUC is associated with a higher risk of recurrent disease and cancer-specific mortality. This information may be useful in refining surveillance protocols and in more appropriate selection of patients for adjuvant chemotherapy.
authors.affiliation: University of Michigan, Ann Arbor, MI 48109, USA. jefwheat@med.umich.edu
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Wheat
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.forename: J Stuart
authors.initials: JS
authors.lastname: Wolf
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.forename: Marco
authors.initials: M
authors.lastname: Roscigno
authors.forename: Eiji
authors.initials: E
authors.lastname: Kikuchi
authors.forename: Richard
authors.initials: R
authors.lastname: Zigeuner
authors.forename: Cord
authors.initials: C
authors.lastname: Langner
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Koppie
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.forename: Mario
authors.initials: M
authors.lastname: Fernández
authors.forename: Pierre
authors.initials: P
authors.lastname: Karakiewizc
authors.forename: Umberto
authors.initials: U
authors.lastname: Capitanio
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Patard
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000175:diagnosis / Q000401:mortality / Q000601:surgery; D002278:Carcinoma in Situ / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D009392:Nephrectomy / Q000379:methods; D010173:Palpation / Q000379:methods*; D011379:Prognosis; D012008:Recurrence; D012189:Retrospective Studies; D012306:Risk; D014513:Ureter / Q000601:surgery*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis / Q000401:mortality / Q000601:surgery*; D014551:Urinary Tract / Q000601:surgery; D019459:Urothelium / Q000601:surgery*