Outcome prediction with p53 immunostaining after radical prostatectomy in patients with locally advanced prostate cancer

Purpose: Conventional pathological variables in prostate cancer may not provide optimal prediction of patient outcome. Pathological findings and p53 immunostaining were measured prospectively in radical prostatectomy specimens to determine the incremental improvement in prediction of patient outcome over clinical findings. Materials and Methods: From a previous prospective study of 392 consecutive patients with prostate cancer who did not receive preoperative therapy and were treated with radical prostatectomy 25 had pathological stage pT3aN0M0, 24 had pT3bN0M0, 2 had pT2bN1M0, 7 had pT3aN1M0 and 14 had pT3bN1 prostate cancer. These locally advanced stage cases comprise the current study population and further analysis was done with p53 immunostaining. All prostate specimens were totally embedded, serially sectioned and whole mounted. We examined pathological, clinical and laboratory findings as well as p53 immunostaining. Results: Median followup was 5.4 years (range 0.5 to 6.4). Univariate analysis revealed that pathological stage, 10% or greater immunostaining for p53, area and length of extraprostatic cancer extension, and cancer volume (all p ≤0.03) were associated with biochemical (prostate specific antigen) or clinical failure. When all variables were considered in stepwise multivariate analysis none attained statistical significance after p53 status entered the model (p <0.01, risk ratio 2.9 for 10% or greater versus less than 10%, 95% confidence interval 1.4-6.2). The concordance index analysis for the predictive ability of prostate specific antigen, stage, grade and ploidy (c = 0.66) was inferior to the predictive ability of a statistical model also including p53 status (c = 0.71). Conclusions: In cases of locally advanced stage cancer p53 immunoreactivity after radical prostatectomy improves outcome prediction. Addition of this variable to those routinely determined may identify a subset of patients who would benefit from more intensive postoperative surveillance and adjuvant therapy.