The dual 5-alpha-reductase inhibitor dutasteride induces atrophic changes and decreases relative cancer volume in human prostate.
OBJECTIVE
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.
Iczkowski
Kenneth A
KA
Department of Pathology and Laboratory Medicine, Veterans Affairs Medical Center, Gainesville, Florida 32608-1197, USA. iczkoka@pathology.ufl.edu
Qiu
Jingxin
J
Qian
Junqi
J
Somerville
Matthew C
MC
Rittmaster
Roger S
RS
Andriole
Gerald L
GL
Bostwick
David G
DG
D058891:5-alpha Reductase Inhibitors; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D000368:Aged; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001284:Atrophy; D001378:Azasteroids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D000068538:Dutasteride; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors*; D010865:Pilot Projects; D011467:Prostate / Q000187:drug effects* / Q000473:pathology; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology / Q000601:surgery; D017154:Stromal Cells / Q000187:drug effects / Q000473:pathology
D058891:5-alpha Reductase Inhibitors; D018931:Antineoplastic Agents, Hormonal; D001378:Azasteroids; D009363:Neoplasm Proteins; D000068538:Dutasteride