Prognostic factors in transitional cell cancer of the bladder: an emergingrole for Bcl-2 and p53

Background and purpose: In a recent study on patients with transitional cel l cancer of the bladder treated with curative radiotherapy following TUR-T, we demonstrated that a low apoptotic index and p53 positivity were associa ted with poor local control. The purpose of this study was to assess the pr ognostic significance of additional markers implicated in regulation of cel l cycle and apoptosis. Patients and Methods: Bcl-2, Bax and p21 positivity were detected immunohis tochemic ally on paraffin-embedded pre-treatment biopsies from 83 patients with invasive transitional cell cancer (TCC) of the bladder, treated with r adiotherapy. In addition, markers determined in an earlier analysis, i.e.: p53, apoptotic index, cyclin D1, retinoblastoma protein and Ki-67 were incl uded in the multivariate analysis. A stepwise proportional hazard analysis was performed, adjusting for classic prognostic factors (T-stage, grade, mu ltifocality and macroscopic completeness of the TUR). Positivity was define d as >10% of tumor cells staining positive for Bcl-2, Bax and p21, and >20% for p53. Results: Bcl-2 positivity was found in 63%, Bax was positive in 52% and p21 in 55% of cases. In the PH analysis Bcl-2 positivity was found to be relat ed to poor local control (36 vs. 72% at 3 years; P = 0.003), as well as to shorter disease-specific survival (74 vs. 94% at 3 years; P = 0.017). Evide nce for an adverse effect of p53 positivity was also found (local control: 32 vs. 69% at 3 years; P = 0.037, disease-specific survival: 76 vs. 92% at 3 years; P = 0.043). In an additional PH analysis, we found poor local cont rol rates for bladder cancers with combined Bcl-2 and p53 positivity (17 vs . 65% at 3 years; P = 0.0017), and lower disease specific survival (60 vs. 92%; P = 0.0024), disease-free survival (7 vs. 35%, P = 0.0023) and overall survival (39 vs. 80%; P = 0.0018). Conclusion: This study provides evidence for a poor outcome in patients tre ated with radiotherapy for TCC of the bladder expressing both Bcl-2 and p53 . This relationship was found for local control and disease-free, disease-s pecific and overall survival. (C) 2001 Elsevier Science Ireland Ltd. All ri ghts reserved.