title: Does preoperative symptom classification impact prognosis in patients with clinically localized upper-tract urothelial carcinoma managed by radical nephroureterectomy?
abstract: OBJECTIVE
  To evaluate if preoperative symptom classification could refine prediction of outcomes for patients with clinically localized upper-tract urothelial carcinoma (UTUC) managed by radical nephroureterectomy (RNU).
  
  
  METHODS
  Data on 654 patients with localized UTUC who underwent RNU were reviewed. Preoperative symptoms were classified as incidental (S1), local (S2), and systemic (S3). Clinical and pathologic data were compared between the cohorts. Kaplan-Meier analyses and Cox proportional hazard modeling were used to determine recurrence-free and cancer-specific survival amongst the symptom cohorts.
  
  
  RESULTS
  Symptom classification was S1 in 213 (33%) patients, S2 in 402 (61%), and S3 in 39 (6%). S3 symptoms were associated with advanced pathology, including higher stage, grade, and lymph node (LN) positivity. Five and 10-year recurrence-free and cancer-specific survival estimates were similar for patients with S1 and S2 symptoms (P = 0.75 and 0.58, respectively), but was worse for patients with S3 symptoms (P < 0.001 for both). On multivariate analysis adjusting for final pathologic stage, grade, and LN status, S3 symptoms were not an independent predictor of recurrence (HR 1.44, P = 0.19) or death due to disease (HR 1.66, P = 0.07). Addition of symptom classification, however, increased the accuracy of a model consisting of stage, grade, and LNs for prediction of recurrence-free and cancer-specific survival by 1.4% and 1.3%, respectively (P < 0.001 for both).
  
  
  CONCLUSIONS
  Local symptoms do not confer worse prognosis compared with patients with incidentally detected UTUC. However, systemic symptoms are associated with worse outcomes despite apparently effective RNU. Patients with systemic symptoms may harbor micrometastatic disease and could potentially benefit from a more rigorous metastatic evaluation or perioperative chemotherapy regimens.
authors.affiliation: New York-Presbyterian Hospital-Weill Cornell Medical Center, New York, NY 10021, USA. jraman@hmc.psu.edu
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
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: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.forename: Jeffery C
authors.initials: JC
authors.lastname: Wheat
authors.forename: Casey K
authors.initials: CK
authors.lastname: Ng
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.forename: Matthias
authors.initials: M
authors.lastname: Waldert
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000145:classification* / Q000401:mortality* / Q000601:surgery; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009392:Nephrectomy; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011379:Prognosis; D016016:Proportional Hazards Models; D014516:Ureteral Neoplasms / Q000145:classification* / Q000401:mortality* / Q000601:surgery