title: Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder.
abstract: OBJECTIVE
  Tissue-based markers improve the accuracy of prediction models in urothelial carcinoma of the bladder (UCB). Current smoking status and cumulative exposure also affect outcomes. To evaluate whether the combination of molecular markers and smoking features further improved the prognostication of patients who underwent radical cystectomy (RC) for UCB.
  
  
  METHODS
  A total of 588 patients underwent RC and bilateral lymphadenectomy for UCB from 1995 to 2005. Immunohistochemistry for p53, p21, pRB, p27, Ki-67, and survivin was performed on tissue microarrays from the RC specimen. Smoking features were routinely assessed at diagnosis. Multivariable Cox regression models assessed time to disease recurrence and cancer-specific mortality.
  
  
  RESULTS
  Of the 588 patients, 128 were never (22%), 283 former (48%), and 177 current smokers (30%). In total, 227 patients experienced disease recurrence, whereas 190 died of UCB. Smoking status was independently associated with both outcomes (hazard ratio [HR] = 1.48 and 2.62, for former and current vs. never smokers, respectively, P<0.001). All markers were significantly associated with both outcomes (P<0.05) except for survivin. The combination of the 4 cell cycle markers p53, p21, pRB, and p27 increased the discrimination of clinicopathologic model for former and current vs. never smokers with c-indices 0.779 and 0.780, respectively (base model c-indices of 0.741 and 0.740 for former and current vs. never smokers, respectively). The further addition of smoking features and biomarker status improved the discrimination of the model (c-indices of 0.783 and 0.786 for former and current vs. never smokers, respectively).
  
  
  CONCLUSIONS
  We confirmed that smoking information and tissue markers status improve prognostication of UCB outcomes after RC; the combination of both reaching the highest level of discrimination.
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY.
authors.forename: Lily C
authors.initials: LC
authors.lastname: Wang
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France.
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Kent
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Kluth
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY.
authors.forename: Asha
authors.initials: A
authors.lastname: Jamzadeh
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY.
authors.forename: Malte
authors.initials: M
authors.lastname: Rieken
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY.
authors.forename: Bashir
authors.initials: B
authors.lastname: Al Hussein Al Awamlh
authors.affiliation: Department of Urology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Quoc-Dien
authors.initials: QD
authors.lastname: Trinh
authors.affiliation: Department of Urology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Maxine
authors.initials: M
authors.lastname: Sun
authors.affiliation: Department of Urology, University of Montreal, Montreal, Quebec, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.affiliation: Department of Urology, University of Padua, Padua, Italy.
authors.forename: Giacomo
authors.initials: G
authors.lastname: Novara
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY.
authors.forename: James
authors.initials: J
authors.lastname: Chrystal
authors.affiliation: Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Zerbib
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Centre, Dallas, TX.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY.
authors.forename: Andrew
authors.initials: A
authors.lastname: Vickers
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Division of Medical Oncology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY. Electronic address: sfshariat@gmail.com.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015331:Cohort Studies; D015653:Cystectomy / Q000401:mortality*; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008197:Lymph Node Excision / Q000401:mortality; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D012907:Smoking / Q000401:mortality*; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarkers; Prognostic; Radical cystectomy; Smoking; Survival; Urothelial carcinoma of the bladder