Lily C Wang1, Evanguelos Xylinas2, Matthew T Kent3, Luis A Kluth4, Michael Rink4, Asha Jamzadeh1, Malte Rieken1, Bashir Al Hussein Al Awamlh1, Quoc-Dien Trinh5, Maxine Sun5, Pierre I Karakiewicz5, Giacomo Novara6, James Chrystal1, Marc Zerbib7, Douglas S Scherr1, Yair Lotan8, Andrew Vickers3, Shahrokh F Shariat9. 1. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY. 2. 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. 3. Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY. 4. Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 5. Department of Urology, University of Montreal, Montreal, Quebec, Canada. 6. Department of Urology, University of Padua, Padua, Italy. 7. Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France. 8. Department of Urology, University of Texas Southwestern Medical Centre, Dallas, TX. 9. 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.
Abstract
OBJECTIVES: 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. MATERIALS AND 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.
OBJECTIVES: 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. MATERIALS AND 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: Devin C Koestler; Joseph Usset; Brock C Christensen; Carmen J Marsit; Margaret R Karagas; Karl T Kelsey; John K Wiencke Journal: Cancer Epidemiol Biomarkers Prev Date: 2016-12-13 Impact factor: 4.254