Early Results of the Value of p53 in Predicting Survival in a Homogeneous Cohort of Patients with Invasive Bladder Cancer Treated with a Neoadjuvant Carboplatin-Based Regimen (M-CAVI)

Abstract

Aims and Background

Several reports on prognostic factors for infiltrating bladder cancer have given controversial results. We assessed the prognostic value of p53 nuclear overexpression together with known prognostic factors for survival in patients with invasive T2-4 NO MO bladder cancer treated with neoadjuvant chemotherapy.

Study Design

Thirty-five paraffi-nized tumor samples from initial transurethral resection of patients with bladder cancer were analyzed immunohistochemi-cally to detect overexpression of p53 protein. Patients were treated with 3 to 4 cycles of neoadjuvant methotrexate, carboplatin, and vinblastine (M-CAVI) and then underwent radical cystectomy. Prechemotherapy, treatment, and postchemotherapy factors were analyzed for correlation with survival by univariate and multivariate analysis. Fifty-seven percent of tumors were positive for p53 protein, 71.5% had grade III-IV tumors, and 72% had organ-confined disease. The median follow-up was 20 months (range 5-71+).

Results

By univariate analysis, the significant pretreatment factors were initial tumor (T) stage (P <0.0001) and the male sex (P = 0.03). Five postchemotherapy variables were found significant: surgery performed according to protocol (P = 0.003), overall clinical (P = 0.004), and overall pathologic (P = 0.02) response to therapy, postchemotherapy pathologic stage (P = 0.0002), and tumor status after surgery (P = 0.0006). By multivariate analysis, the initial prechemotherapy T stage was the only factor that demonstrated independent significance.

Conclusions

Although the median follow-up of the study is still too short, in this group of patients treated with a neoadjuvant carboplatin-based regimen, a classical variable (prechemotherapy T stage) rather than p53 nuclear overexpression was an independent prognostic factor for survival. Further follow-up will be required to assess the value of p53 overexpression as a prognostic factor in invasive bladder cancer patients treated with neoadjuvant carboplatin-based chemotherapy.