The dual 5-alpha-reductase inhibitor dutasteride induces atrophic changes and decreases relative cancer volume in human prostate. Urology 2005 Jan;65(1):76-82
Date
01/26/2005Pubmed ID
15667867DOI
10.1016/j.urology.2004.08.042Abstract
OBJECTIVES: To perform the first evaluation of the effects of the 5-alpha-reductase inhibitor class of drugs on cancer histopathologic features at radical prostatectomy in a placebo-controlled multicenter trial.
METHODS: We analyzed prostatectomy slides in a blinded manner from 17 men treated with dutasteride, an inhibitor of types 1 and 2 isoenzymes of 5-alpha-reductase, and 18 men treated with placebo for 5 to 11 weeks before radical prostatectomy. The histopathologic features of benign epithelium, high-grade prostatic intraepithelial neoplasia, and cancer were recorded, and the treatment effect was scored. Digital imaging analysis was used to measure the stroma/epithelium ratio and epithelial height, as well as the nuclear area in cancer.
RESULTS: In benign epithelium, treatment caused distinctive cytoarchitectural changes of atrophy and a decrease in the epithelial height (P = 0.053). The peripheral zone showed the most marked response to treatment. In cancer tissue, the tumor volume was significantly lower in the dutasteride-treated men than in the placebo-treated men (mean 15% versus 24%, respectively, P = 0.025), the percentage of atrophic epithelium was increased (P = 0.041), and the stroma/gland ratio was doubled (P = 0.046). The treatment alteration effect score was doubled (P = 0.055) and did not correlate with any Gleason score changes.
CONCLUSIONS: After short-term dutasteride treatment, benign epithelium showed involution and epithelial shrinkage, and prostate cancer tissue demonstrated a decrease in epithelium relative to stroma. These findings indicate that dutasteride induces significant phenotypic alterations in both the benign and the neoplastic prostate, supportive of a chemopreventive or chemoactive role.
Author List
Iczkowski KA, Qiu J, Qian J, Somerville MC, Rittmaster RS, Andriole GL, Bostwick DGAuthor
Kenneth A. Iczkowski MD Professor in the Pathology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
5-alpha Reductase InhibitorsAdenocarcinoma
Aged
Antineoplastic Agents, Hormonal
Atrophy
Azasteroids
Combined Modality Therapy
Double-Blind Method
Dutasteride
Epithelial Cells
Humans
Image Processing, Computer-Assisted
Male
Middle Aged
Neoadjuvant Therapy
Neoplasm Proteins
Pilot Projects
Prostate
Prostatectomy
Prostatic Intraepithelial Neoplasia
Prostatic Neoplasms
Stromal Cells
