BIOSTATISTICAL MODELING USING TRADITIONAL VARIABLES AND GENETIC BIOMARKERS FOR PREDICTING THE RISK OF PROSTATE CARCINOMA RECURRENCE AFTER RADICAL PROSTATECTOMY

BACKGROUND. Approximately 50-60% of patients treated with radical pros tatectomy for clinically localized prostate carcinoma are found to hav e microscopic disease that is not organ-confined, and a significant po rtion of these patients will relapse. Multiple studies have attempted to identify these high risk patients by evaluating many potential prog nostic variables. These studies, however, have not included the more r ecent molecular biomarkers found to be independent predictors of disea se recurrence. METHODS. One hundred thirty-two patients who underwent radical prostatectomy at one center between 1986 and 1993 were subject ed to a multivariable Cox regression analysis to determine the preoper ative and postoperative variables that remain significant predictors f or the likelihood of serologic recurrence. The preoperative variables included in the model were age, race, and prostate specific antigen(PS A); the postoperative variables were Gleason sum, nuclear grade, patho logic stage (capsular status), p53 tumor suppressor gene expression, b cl-2 protooncogene expression, and proliferative biomarker Ki-67 expre ssion. Biomarkers were also evaluated separately. RESULTS. A model tva s developed using only variables that remained significant predictors for the likelihood of recurrence. The following equation calculated th e relative risk of recurrence: R(w) = exp [(0.70 x Race) + (0.79 x PSA {4.1-10}) + (1.34 x PSA{>10}) + (0.91 x Organ confinement) + (0.65 x p 53{1,2+}) + (1.45 x p53{3,4+}) + (0.70 x bcl-2)]. This equation catego rized men into 3 distinct risk groups (low: R(r) < 5.0; intermediate: R(r) = 5.0-15.0; high risk: R(r) > 15.0). CONCLUSIONS. This equation a llows patients at high risk for PSA recurrence to be identified shortl y after radical surgery. These patients at high risk for serologic rec urrence and eventual progression may be considered for currently accep ted adjuvant therapy or enrollment in clinical trials for the newer in vestigational therapies for locally advanced prostate carcinoma. (C) 1 997 American Cancer Society.