title: Continuous finasteride therapy for benign prostate hypertrophy upgrades both neuroendorcine differentiation and aggressive prostate cancer.
abstract: Finasteride has been recognized as a drug suitable for the chemoprevention of prostate cancer (PC) by reducing intracellular dihydrotestosterone (DHT) levels. The Prostate Cancer Prevention Trial (PCPT) database on continuous finasteride treatment of almost 19 thousands patients indicated the reduction in cancer prevalence by about 25% . However, in this same study more than a twofold increase in high grade aggressive prostate tumors was recorded when compared to controls thus arising serious doubts upon the real benefits of the protocol. Here, our investigation was performed three years on a continuous versus intermittent (six month treatment followed by 6 months resting period) finasteride treatment in 125 BPH patients (pts) each. The overall PC prevalence in both finasteride-treated groups was lower that in untreated controls and thus being in accordance with the PCPT data. However, continuous therapy gave significantly higher incidence in Gleason score (GS)>6 carcinomas compared to intermitted therapy and controls (44.5%, 25% and 18.2% of total acquired PC, respectively). In addition, the acquired elevated chromogranin A (CgA) values were also more than doubled in pts treated continuously compared to the other two groups (13.6%, 5.6% and 6.4%, respectively). Acquired PC GS>6 recorded in pts with a raise in CgA was higher in continuously treated pts (50%) than in the other two studied groups (20% and 25%, respectively). In pts with the retained normal CgA concentration highest PC incidence was found in controls (5.1%) and lower prevalence was recorded in continuously (2.8%) and intermittently treated pts (2.5%) while the respective PC GS>6 incidence was lower in controls than in treated pts. Seemingly, finasteride treatment reduces PC prevalence in pts free of NED but elevates the number of aggressive carcinomas in CgA-positive pts only if continuous treatment is applied. In conclusion, current chemoprevention protocols need to be carefully reconsidered prior to the selection between continuous and discontinued finasteride treatment.
authors.affiliation: Department of Oncology and Nuclear Medicine, University Hospital Sestre Milosrdnice, 10000 Zagreb, Croatia. marko_tarle@yahoo.com
authors.forename: Marko
authors.initials: M
authors.lastname: Tarle
authors.forename: Borivoj
authors.initials: B
authors.lastname: Spajic
authors.forename: Ivo
authors.initials: I
authors.lastname: Kraljic
authors.forename: Zvonko
authors.initials: Z
authors.lastname: Kusic
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D018120:Finasteride / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D009490:Neurosecretory Systems / Q000473:pathology*; D011470:Prostatic Hyperplasia / Q000188:drug therapy*; D011471:Prostatic Neoplasms / Q000473:pathology*
chemical_list: D004791:Enzyme Inhibitors; D018120:Finasteride