Preliminary evaluation of the effect of dutasteride on PCA3 in post-DRE urine sediments: a randomised, open-label, parallel-group pilot study

van Gils MPMQ, Hessels D, Peelen WP, Vergunst H, Mulders PFA, Schalken JA. Prostate 2009;69:1624-34

• This pilot study evaluated the effect of 3- month treatment with the 5α-reductase inhibitor dutasteride 0.5 mg and 3.5 mg once daily (od) on the PCA3 Score in men with lower urinary tract symptoms (LUTS)/benign prostatic hyperplasia (BPH) or with biopsy-proven, clinically localised PCa
• Please note that the PROGENSA™ PCA Assay was not used in this study. Instead a research protocol using urine sediments was performed. A total of 25 subjects were randomised: 8 LUTS/BPH patients to dutasteride 0.5 mg od; 8 LUTS/BPH patients to dutasteride 3.5 mg od; 5 PCa patients to dutasteride 0.5 mg od; 4 PCa patients to dutasteride 3.5 mg od
• The effect of dutasteride on the PCA3 Score was not consistent in all four groups; it varied between groups, between subjects within one group and also in subjects over time
• In contrast, the effect of dutasteride on e.g. serum dihydrotestosterone (reduction >= 90%), prostate volume (reduction 10-16%) and serum prostate specific antigen (PSA; reduction around 50%) were time dependent, consistent and as expected
• It was concluded that in this small-size, exploratory pilot study the effect of dutasteride on the PCA3 Score was variable and requires further evaluation

Reviewed by

Prof. J. Schalken

Editorial comment

The effect of endocrine treatment on biomarkers that are regulated by the androgen receptor is well documented, e.g. serum values drop by about 50 %. This is the first report to address this issue for PCA3. PCA3 is also regulated by the androgen receptor, hence an influence of endocrine therapy on PCA3 values needed to be studied. The study is preliminary and points in a direction that the influence of dutasteride on the PCA3 score is variable. Differences in androgen receptor activity in cancer versus normal cells and the fact that PCA3 is strongly over expressed in cancer cells (whereas PSA mRNA is similar between cancer and normal) make it rather a tough equation with too many unknowns. The study stresses the need to further evaluate the effect and for the time being PCA3 scores after endocrine therapy cannot be interpreted in the light of the currently available literature.

More information

http://www.ncbi.nlm.nih.gov/pubmed/19588525?itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum&ordinalpos=9