P53 expression in patients with advanced urothelial cancer of the urinary bladder

Study Type - Prognosis (inception cohort) Level of Evidence 1b Objective To test whether assessing p53 expression could improve the ability to predict disease recurrence and disease-specific survival in a multi-institutional cohort of patients with advanced urothelial carcinoma of the urinary bladder (UCB). Patients and Methods The study comprised 692 patients with pT3-4 N0 or pTany N+ UCB treated with radical cystectomy and lymphadenectomy. The predictive accuracy (PA) was quantified using the 200 bootstrap-corrected concordance index. The base model comprised age, gender, stage, grade, lymphovascular invasion, number of lymph nodes removed, number of lymph nodes positive, concomitant carcinoma in situ, and adjuvant chemotherapy. Results p53 expression was altered in 341 (49.3%) patients. In multivariable analyses, p53 expression was independently associated with disease recurrence (hazard ratio, 1.66; P < 0.001) and cancer-specific mortality (hazard ratio 1.65, P < 0.001). Overall, adding p53 did not significantly improve the PA of the base model (recurrence +0.7%, P = 0.085, and cancer-specific mortality +1.2%, P = 0.050). In the subgroups of pT3N0 (280) and pT4N0 (83) patients, p53 slightly improved the PA of the base model by a statistically significant degree (recurrence +1.7% and +3.6%, respectively; cancer-specific mortality +1.9% and +3.5%, respectively; all P < 0.001). In 329 patients with pTany N+ disease p53 status did not improve the PA of the base model. Conclusion While assessing p53 expression has limited utility in patients with lymph node-positive UCB, it marginally improves prognostication in patients with advanced non-metastatic UCB. Integration of p53 into a panel of biomarkers might be necessary to capture a more accurate picture of the biological potential of advanced UCB.