The dual 5-alpha-reductase inhibitor dutasteride induces atrophic changes and decreases relative cancer volume in human prostate.

Abstract

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.

• Authors: Kenneth A Iczkowski, Jingxin Qiu, Junqi Qian, Matthew C Somerville, Roger S Rittmaster, Gerald L Andriole, David G Bostwick
• Journal: Urology (Urology) Vol. 65 Issue 1 Pg. 76-82 (Jan 2005) ISSN: 1527-9995 [Electronic] United States
• PMID: 15667867 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial)

Chemical References

• 5-alpha Reductase Inhibitors
• Antineoplastic Agents, Hormonal
• Azasteroids
• Neoplasm Proteins
• Dutasteride

Topics

• 5-alpha Reductase Inhibitors
• Adenocarcinoma (drug therapy, enzymology, pathology, surgery)
• Aged
• Antineoplastic Agents, Hormonal (administration & dosage, pharmacology, therapeutic use)
• Atrophy
• Azasteroids (administration & dosage, pharmacology, therapeutic use)
• Combined Modality Therapy
• Double-Blind Method
• Dutasteride
• Epithelial Cells (drug effects, pathology)
• Humans
• Image Processing, Computer-Assisted
• Male
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Proteins (antagonists & inhibitors)
• Pilot Projects
• Prostate (drug effects, pathology)
• Prostatectomy
• Prostatic Intraepithelial Neoplasia (drug therapy, enzymology, pathology, surgery)
• Prostatic Neoplasms (drug therapy, enzymology, pathology, surgery)
• Stromal Cells (drug effects, pathology)