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

We are attempting to develop a method to predict hormonal response in patients with carcinoma of the prostate. We have measured multiple biochemical variables and determined Gleason grade 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 receptor content, and tissue testosterone and dihydrotestosterone content. The 16 patients were followed prospectively and the response of each patient to hormonal therapy was assessed clinically. Two groups of patients were identified: 1 group of 7 patients in which the mean duration of response was 7.7 plus or minus 1.5 months (plus or minus standard error) and in which all patients have relapsed and died of their disease, and a second group of 9 patients in which the mean duration of response was 18.6 plus or minus 1.6 months (plus or minus standard error) and in which 7 of the 9 patients (78 per cent) are still responding. The 2 groups were statistically different (p less than 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 less than 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 less than 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.