Is There A Role for Testosterone Therapy in the Treatment of Metastatic Prostate Cancer?

There has long been a discussion about the possible effects of using testosterone as a treatment for men with advanced metastatic prostate cancer.  In a poster presentation at ASCO 2019, it was shown that there are androgen receptor changes in the circulating-tumor DNA (ctDNA) in men with metastatic castration-resistant prostate cancer (mCRPC) treated with high-dose testosterone. 

In a small study involving 33 consecutive men coming into a clinic with mCRPC were treated with at least one round of high-dose testosterone (HDT).  They were evaluated to determine the relationship of androgen receptor (AR) gene alterations to the high dose testosterone (HDT) responsiveness. 

Baseline ctDNA analysis at 4.2 months revealed that there were AR alterations with the use of the testosterone therapy and 29% of men exhibiting PSA ≥50% response and 45% exhibiting PSA ≥30% response. 

Only grade 3 or higher adverse events were reported in 6% of the men. Among the men with baseline AR alterations who received HDT treatment, repeated ctDNA analysis revealed decreased alterations in 100% of the men. 

There was no clear relationship identified between PSA response and baseline ctDNA AR characteristics.

These findings demonstrate both the safety and efficacy of using HDT in a subset of men with mCRPC. Additional studies investigating the relationship between genomic alterations and responsiveness to HDT are warranted before it should be considered for general clinical use.

MW Moses, E Ledet, C Manogue, et al