Correlation of Prostatic Nuclear Androgen Receptor Content with Duration of Response and Survival Following Hormonal Therapy in Advanced Prostatic Cancer

Abstract

To assess whether pre-treatment prostatic androgen receptor measurements would be of value in predicting the response to hormonal therapy in patients with prostatic cancer 23 men with metastatic carcinoma of the prostate underwent prostatic biopsy before treatment. Cytosolic and nuclear prostatic androgen receptor contents were measured by a single saturating dose, dextran-charcoal assay. All patients had measurable levels of androgen receptor in prostatic tissue and all demonstrated objective evidence of improvement following hormonal therapy. Thus, if androgen receptor measurements are to be useful in predicting prognosis correlations between quantitative levels of receptor and quantitative aspects of response must be established. In our study response was quantitated by measuring the duration of response and survival following hormonal treatment. The strong correlation between duration of response and survival (p less than 0.01) demonstrated herein suggests that survival in these patients is related directly to the duration of time patients respond to hormonal therapy. Neither total cellular nor cytosolic androgen receptor content correlated with response. However, nuclear androgen receptor content correlated with the duration of response and survival following hormonal treatment (p less than 0.05). Furthermore, in patients with nuclear receptor levels less than 110 fmol. per mg. deoxyribonucleic acid the duration of response (7.1 plus or minus 3.8 months) and survival (14.4 plus or minus 5.9 months) was significantly shorter than in patients with higher levels of nuclear receptor (17.3 plus or minus 10.4 and 24.7 plus or minus 8.8 months, respectively) (p less than 0.05). These findings, which are the first report of a correlation between nuclear androgen receptor content and hormonal responsiveness, suggest that measurements of nuclear receptor may aid in identifying those patients unlikely to obtain a prolonged response from hormonal therapy.