The number of patients diagnosed with prostate cancer (CaP) has increased 63% in the last seven years. Over the same time period, the number of deaths has risen from 24,000 to 32,000 cases a year. With the aging of the American male population and the increased use of screening for CaP, these figures can only be expected to rise over the coming years. Although increased numbers of patients are currently being diagnosed with localized CaP, the malignant potential of an individual tumor cannot be accurately determined with present methodology. Without definition or identification of the malignant potential of the tumor, clinical investigators are unable to distinguish the cancers that will remain dormant from those that will progress and compete as a cause of mortality. For patients who require therapy, current knowledge is also lacking to allow clinicians to predict whether their tumor will respond to radiation therapy. If an accurate marker of tumors malignant potential were found, patients could be offered a more rational approach to therapy that, in many cases, would mean observation alone. Presently, two markers show promise in both these areas, namely tumor ploidy and mutation in the p53 gene. These markers have not yet been evaluated in a large, multi-institutional study. This proposal will study ploidy and p53 in patients with CaP who are entered on an ongoing clinical trial (INT-0086/SWOG-8794). Eligible patients will have been found to be margin positive after radical prostatectomy and thus have a high likelihood of disease progression. In this trial, patients are randomized to observation or adjuvant radiation therapy. The usefulness of these markers will then be evaluated utilizing specimens of 558 patients from this large multi-institutional trial. Specific aims of this proposal include the following: 1) to evaluate the clinical usefulness of DNA ploidy of a prostate biopsies; 2) to determine whether the ploidy of the positive margins predicts clinical outcome; 3) to determine whether ploidy is a stronger predictor of outcome than whether the patient receives adjuvant radiation therapy; 4) to determine whether the p53 status of the tumor is an accurate predictor of malignant potential and response to radiation therapy; and 5) to evaluate whether determining the ploidy and p53 status of the tumor gives additive information. Determination of the usefulness of these markers in CaP may be an initial step in the rationalization and individualization of treatment of patients with localized CaP.