p53 and p21 expression levels predict organ preservation and survival in invasive bladder carcinoma treated with a combined‐modality approach

Abstract

BACKGROUND The purpose of the current study was to evaluate the expression levels of p53, p21 and pRB as predictors of for long‐term organ preservation and survival in patients with bladder carcinoma who were treated with bladder‐sparing intent using a combined‐modality approach. METHODS Tumor samples from 82 consecutive patients with localized invasive bladder carcinoma treated on 3 different bladder‐sparing studies were examined for p53, p21, and pRB expression by immunohistochemical methods. Treatment consisted of transurethral resection, platinum‐based neoadjuvant chemotherapy, and, according to response, either radiotherapy or radical cystectomy. The median follow‐up duration was 55 months. RESULTS Positive immunoreactivity for p53, p21, and pRB was observed in 47%, 52%, and 67% of patients, respectively. Positive p53 immunoreactivity and positive p21 immunoreactivity were independent predictors of decreased survival with bladder preservation (P = 0.02 and P = 0.02, respectively) and disease‐free survival (DFS; P = 0.005 and P = 0.009, respectively) in a multivariate analysis adjusting for clinical stage, ureteral obstruction, and age. Regarding overall survival (OS), p53 overexpression was associated with poor outcome (P = 0.03), whereas the association of poor outcome with p21 expression did not reach statistical significance (P = 0.07). No association between pRB immunoreactivity and outcome was found. When the combined expression of p53 and p21 was assessed, the positive expression of both markers was a strong and unfavorable prognostic factor for survival with bladder preservation (P = 0.006), DFS (P = 0.003), and OS (P = 0.02). CONCLUSIONS Expression levels of p53 and p21, especially when simultaneously assessed, exhibit independent predictive value for long‐term bladder preservation and survival in patients with bladder carcinoma treated with combined‐modality therapy. These determinations could be useful in the selection of candidates for bladder‐preserving treatment. Cancer 2004. © 2004 American Cancer Society.