Combining smoking information and molecular markers improves prognostication in patients with urothelial carcinoma of the bladder.
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.
['Wang|Lily C|LC|', 'Xylinas|Evanguelos|E|', 'Kent|Matthew T|MT|', 'Kluth|Luis A|LA|', 'Rink|Michael|M|', 'Jamzadeh|Asha|A|', 'Rieken|Malte|M|', 'Al Hussein Al Awamlh|Bashir|B|', 'Trinh|Quoc-Dien|QD|', 'Sun|Maxine|M|', 'Karakiewicz|Pierre I|PI|', 'Novara|Giacomo|G|', 'Chrystal|James|J|', 'Zerbib|Marc|M|', 'Scherr|Douglas S|DS|', 'Lotan|Yair|Y|', 'Vickers|Andrew|A|', 'Shariat|Shahrokh F|SF|']
D000368:Aged D014408:Biomarkers, Tumor D015331:Cohort Studies D015653:Cystectomy D005500:Follow-Up Studies D006801:Humans D007124:Immunoenzyme Techniques D008197:Lymph Node Excision D008207:Lymphatic Metastasis D008297:Male D008875:Middle Aged D060787:Neoplasm Grading D009364:Neoplasm Recurrence, Local D009367:Neoplasm Staging D011379:Prognosis D012907:Smoking D015996:Survival Rate D001749:Urinary Bladder Neoplasms
Smoking Prognostic Urothelial carcinoma of the bladder Radical cystectomy Biomarkers Survival