PROGNOSTIC VALUE OF P55 IN MUSCLE-INVASIVE BLADDER-CANCER TREATED WITH PREOPERATIVE RADIOTHERAPY

Objectives, The relationship of p53 mutations. as analyzed immunohisto chemically to radiation response and therapeutic outcome was examined in a cohort of 301 patients with muscle-invasive transitional cell car cinoma of the bladder treated relatively uniformly with preoperative r adiotherapy (50 Gy in 25 fractions) 4 to 6 weeks prior to radical cyst ectomy. Methods. Adequate formalin-fixed paraffin-embedded archival ti ssue for the immunohistochemical staining of p53 using antibody DO1 wa s obtained in 109 patients. The median follow-up for those living was 91 months. Results. Overall, p53 staining was positive in 56% of the c ases, with 60% positive in Stage T2 (n = 48), 42% in Stage T3a (n = 31 ), and 63% in Stage T3b (n = 30), Overexpression of p53 did not correl ate with actuarial local control, distant metastasis freedom, disease freedom, or overall survival. However, significant associations were s een when these analyses were limited to patients with clinical Stage T 3b disease. In this subgroup, the actuarial 5-year rates for patients with p53 positively and negatively stained tumors were 55% and 100%, r espectively, for distant metastasis freedom (P = 0.01), 51% and 91% fo r disease freedom (P = 0.04); and 32% and 91% for overall survival (P = 0.006). Cox proportional hazards models that included p53 staining a nd other prognostic factors of significance in the univariate analyses revealed p53 to be independently predictive of survival for patients with Stage T3b disease. Conclusions. The prognostic value of p53 immun ostaining rested with Stage T3b patients. Although no correlations wer e found with radiation response, p53 positivity in this subgroup was a ssociated with a higher rate of distant metastasis and reduced overall survival. For these patients, p53 negativity would indicate that aggr essive local treatment (that is,preoperative radiotherapy and cystecto my) is sufficient, whereas p53 positivity would indicate that multiage nt chemotherapy is required because of the increased risk of distant m etastasis.