title: High-grade prostate cancer and biochemical recurrence after radical prostatectomy among men using 5α-reductase inhibitors and alpha-blockers.
abstract: BACKGROUND
  Two clinical trials have shown that users of 5α-reductase inhibitors finasteride and dutasteride (5-ARIs) have reduced overall prostate cancer risk, while the proportion of high-grade tumors is increased. We studied tumor characteristics, risk of biochemical recurrence and mortality after radical prostatectomy in 5-ARI and alpha-blocker users.
  
  
  METHODS
  The study cohort consisted of 1,315 men who underwent radical prostatectomy at the Tampere University Hospital during 1995-2009. Biochemical relapse was defined as serum PSA ≥ 0.2 ng/ml after the operation. Information on mortality and medication purchases was obtained from national registries. Cox proportional regression was used to analyze hazard ratios (HRs) and 95% confidence intervals (95% CI) of biochemical relapse and death.
  
  
  RESULTS
  The proportion of high-grade (Gleason 7-10) tumors was significantly elevated among men who had used 5-ARIs for 4 years or longer compared to the non-users (83.3% vs. 53.3%, respectively). Survival curves for biochemical relapse-free survival differed between long-term and short-term 5-ARI users, but the hazard ratio remained statistically non-significant. Risk of biochemical recurrence was elevated among alpha-blocker users (HR 1.68, 95% CI 1.37-2.06), but in sensitivity analyses this was evident only in men using alpha-blockers after prostatectomy. Mortality was not associated with medication usage.
  
  
  CONCLUSIONS
  Long-term users of finasteride or dutasteride had more often high-grade prostate cancer. Our results suggest also worse progression-free survival. The association between risk of biochemical recurrence and post-operative alpha-blocker usage suggests that voiding or storage symptoms after prostatectomy may predict biochemical relapse.
authors: Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. teemu.murtola@uta.fi
authors: Teemu J
authors: TJ
authors: Murtola
authors: Paula M
authors: PM
authors: Kujala
authors: Teuvo L J
authors: TL
authors: Tammela
mesh_terms: D058891:5-alpha Reductase Inhibitors / Q000008:administration & dosage*; D058668:Adrenergic alpha-1 Receptor Antagonists / Q000008:administration & dosage*; D001378:Azasteroids / Q000008:administration & dosage; D015331:Cohort Studies; D018572:Disease-Free Survival; D000068538:Dutasteride; D018120:Finasteride / Q000008:administration & dosage; D005387:Finland / Q000453:epidemiology; D006801:Humans; D007610:Kallikreins / Q000097:blood; D008297:Male; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000097:blood / Q000453:epidemiology / Q000473:pathology / Q000517:prevention & control*; D016016:Proportional Hazards Models; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D011799:Quinazolines / Q000008:administration & dosage; D013449:Sulfonamides / Q000008:administration & dosage; D015996:Survival Rate; D000077409:Tamsulosin
chemical_list: D058891:5-alpha Reductase Inhibitors; D058668:Adrenergic alpha-1 Receptor Antagonists; D001378:Azasteroids; D011799:Quinazolines; D013449:Sulfonamides; D018120:Finasteride; C047638:alfuzosin; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen; D000077409:Tamsulosin; D000068538:Dutasteride