The use of Multiple Variables to Predict Response to Endocrine Therapy in Carcinoma of the Prostate: A Preliminary Report

Abstract

A method to predict hormonal response in patients with carcinoma of the prostate was developed. Multiple biochemical variables were measured and Gleason grade was determined in prostatic needle biopsies obtained from 16 patients immediately before castration or initiation of estrogen therapy. Biochemical variables included 6 enzymes (3 enzymes involved in androgen metabolism and 3 hydrolytic enzymes), androgen rceptor content, and tissue testosterone and dihydrotestosterone content. The 16 patients were followed prospectively and the response of each patient to hormonal theapy was assessed clinically. Two groups of patients were identified: 1 group of 7 patients in which the mean duration of response was 7.7 .+-. 1.5 mo. (.+-. standard error) and in which all patients have relapsed and died of their disease, and a 2nd group of 9 patients in which the mean duration of response was 18.6 .+-. 1.6 mo. (.+-. standard error) and in which 7 of the 9 patients (78 %) are still responding. The 2 groups were statistically different (P < 0.001) in terms of duration of response. The 2 groups could not be distinguished by Gleason grade, single enzymatic activities or tissue androgen content. The mean value of nuclear salt extractable androgen receptor was statistically different between the 2 groups (P < 0.05) but with considerable overlap of individual patients between the 2 groups. An index was developed based on multiple enzymatic activities, which separated the 2 response groups better than any single variable alone (P < 0.02). When salt extractable nuclear androgen receptor was included in the numerator of this index the 2 groups were separated almost completely. This preliminary study suggests that the measurement of multiple biochemical variables may be useful in predicting hormonal response.