Association of Clinical Benign Prostate Hyperplasia with Prostate Cancer Incidence and Mortality Revisited: A Nationwide Cohort Study of 3 009 258 Men

BackgroundAlthough benign prostate hyperplasia (BPH) and prostate cancer (PCa) share features such as hormone-dependent growth and response to treatment with antiandrogen therapy, BPH is generally not considered a premalignant lesion.ObjectiveTo determine whether clinical BPH is associated with an increased risk of PCa incidence and mortality.Design, setting, and participantsUsing designs with individual participant data from five national registries, we studied the entire Danish male population from 1980 through 2006, a total of 3 009 258 Danish men. We collected PCa diagnoses (n = 53 315), information on PCa mortality (n = 25 459), and ascertained clinical BPH (not histologically proven BPH) through hospitalization (n = 187 591) and/or surgery (n = 77 698) from 1980 to 2006 and the use of α-adrenergic receptor antagonists (n = 143 365) and/or the use of 5α-reductase inhibitors (5-ARIs) (n = 47 465) from 1995 to 2006.MeasurementsPCa incidence and mortality was assessed for each category of clinical BPH using Kaplan-Meier plots of cumulative incidence and Cox proportional hazard ratios (HRs) adjusted for potential confounders.Results and limitationsFor the entire cohort studies, multivariate-adjusted HRs for PCa incidence were 2.22 (95% confidence interval, 2.13–2.31) in men hospitalized and 3.26 (3.03–3.50) in men operated on for clinical BPH versus general population controls. Corresponding HRs for PCa mortality were 2.00 (1.91–2.08) for hospitalization and 7.85 (7.40–8.32) for surgery. For age-matched cohort studies, corresponding HRs for PCa incidence were 3.04 (2.96–3.13) for hospitalization, 2.60 (2.47–2.73) for surgery, 4.49 (4.33–4.65) for α-adrenergic receptor antagonist use, and 2.54 (2.40–2.68) for 5-ARI use. Each category of clinical BPH has limitations, but limitations differ between the categories and therefore are unlikely to explain the results.ConclusionsIn Danish men followed for up to 27 yr, clinical BPH was associated with a two- to three-fold increased risk of PCa incidence and with a two- to eight-fold increased risk of PCa mortality. These data should not be used to infer causality.