Prostate tissue androgen content predicts ADT outcome

By Sally Robertson, B.Sc.Mar 6 2013

Determining the androgen content in prostate tissue could predict patients' responses to androgen deprivation therapy (ADT) and the risk for castration-resistant prostate cancer (CRPCa), show study findings.

"This is the first report to detail the relationship between pretreatment prostate tissue androgen and response or prognosis of PCa treated by ADT using precise simultaneous quantitative analysis of androgen," say Yasuhiro Shibata (Gunma University Graduate School of Medicine, Japan) and team.

The researchers developed an analytical method utilizing liquid chromatography-tandem mass spectrometry that was sensitive enough to evaluate the tissue androgen content in a single needle biopsy specimen.

They used the technique to determine the pre-ADT prostate tissue androgen content in 165 PCa patients who were followed up for the development of CRPCa, defined as a prostate specific antigen (PSA) value continuously raised by more than 25% above the nadir and a 2.0 ng/mL increase in PSA, and/or the progression of preexisting disease and/or the appearance of new metastasis.

As reported in Andrology, 23 of the individuals developed CRPCa during the treatment period. These individuals had a significantly higher tissue testosterone (T) level and a significantly lower 5a-dihydrotestosterone (DHT) level than those without CRPCa, at medians of 0.98 versus 0.45 pg/mg and 4.92 versus 16.89 pg/mg, respectively. This resulted in a significantly higher tissue T/DHT ratio for those with than without CRPCa, at 0.192 versus 0.056.

A significant difference was also found in response to ADT, with CRPCa patients having shorter PSA half-times, at 19 versus 41 days, compared with nonCRPCa patients, as well as a higher PSA nadir value, at 0.60 versus 0.19 ng/mL.

Furthermore, a multivariate Cox proportional hazard model showed that the pre-ADT tissue T/DHT ratio and Gleason score were significant predictors for CRPCa development, and that these two variables could be used to calculate the relative risk for future CRPCa.

"Previous reports have revealed that, while lowering of the circulating T to a castration level with ADT, its active metabolite DHT still exists in PCa tissues after ADT at levels sufficient to activate AR [androgen receptor]," explains the team.

"The results of this study suggest that the evaluation of prostate androgen content using a single needle biopsy specimen may be useful for predicting future CRPC[a] development after primary ADT," say Shibata et al. "If CRPC[a] candidates could be predicted at the initial induction of ADT, it would be important information for planning the management of PCa patients."

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