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Abstract: Background: It is largely unknown whether prostate-specific antigen (PSA) level at first date of testing predicts long-term risk of prostate cancer (PCa) incidence and mortality in the general population. Objective: Determine whether baseline PSA levels predict long-term risk of PCa incidence and mortality. Design, setting, and participants: We examined 4383 men aged 20–94 yr from the Danish general population in the prospective Copenhagen City Heart Study. PSA was measured in plasma samples obtained in 1981–1983. Measurements: PCa incidence and mortality as a function of baseline PSA was assessed using Kaplan-Meier plots of cumulative incidence and competing risk subhazard ratios. Results and limitations: During 28 yr of follow-up, 170 men developed PCa, and 94 men died from PCa. Median follow-up was 18 yr (range: 0.5–28 yr). For PCa incidence, the subhazard ratio was 3.0 (95% confidence interval [CI], 1.9–4.6) for a PSA level of 1.01–2.00 ng/ml, 6.8 (95% CI, 4.2–11) for PSA 2.01–3.00 ng/ml, 6.6 (95% CI, 3.4–13) for PSA 3.01–4.00 ng/ml, 16 (95% CI, 10.4–25) for PSA 4.01–10.00 ng/ml, and 57 (95% CI, 32–104) for PSA >10.00 ng/ml versus 0.01–1.00 ng/ml. For PCa mortality, corresponding subhazard ratios were 2.2 (95% CI, 1.3–3.9), 5.1 (95% CI, 2.8–9.0), 4.2 (95% CI, 1.8–10), 7.0 (95% CI, 3.8–14), and 14 (95% CI, 6.0–32). For men with PSA levels of 0.01–1.00 ng/ml, the absolute 10-yr risk of PCa was 0.6% for ages <45 yr, 0.7% for ages 45–49 yr, 1.1% for ages 50–54 yr, 1.2% for ages 55–59 yr, 1.3% for ages 60–64 yr, 1.1% for ages 65–69 yr, 1.3% for ages 70–74 yr, and 1.5% for ages ≥75 yr; corresponding values for PSA levels >10.00 ng/ml were 35%, 41%, 63%, 71%, 77%, 69%, 75%, and 88%, respectively. Conclusions: Stepwise increases in PSA at first date of testing predicted a 3–57-fold increased risk of PCa, a 2–16-fold increased risk of PCa mortality, and a 35–88% absolute 10-yr risk of PCa in men with PSA levels >10.00 ng/ml. Equally important, the absolute 10-yr risk of PCa in men with PSA levels 0.01–1.00 ng/ml was only 0.6–1.5%. [Copyright &y& Elsevier]

Abstract: Background: It remains unclear whether adding long-term prostate-specific antigen velocity (PSAV) to baseline PSA values improves classification of prostate cancer (PCa) risk and mortality in the general population. Objective: To determine whether long-term PSAV improves classification of PCa risk and mortality in the general population. Design, setting, and participants: We studied 503 men aged 30–80 yr, with and without PCa, who had repeated PSA measurements over 20 yr and up to 28 yr before PCa diagnosis. These were selected from among 7455 men in the Copenhagen City Heart Study, a prospective, general population study with follow-up from 1981 through 2010. Results were subsequently applied to all 1 351 441 men aged 40–80 yr living in Denmark from 1997 through 2006. Outcome measurements and statistical analysis: PCa risk and mortality were assessed using Cox regression. Improvement in risk classification was assessed using the net reclassification index (NRI). Results: Age-adjusted hazard ratios for PCa risk and mortality were 2.7–5.3 and 2.3–3.4, respectively, for long-term PSAV when added to models already including baseline PSA values. For PCa risk and mortality, adding long-term PSAV to models already including baseline PSA values and age yielded continuous NRIs of 98–99% and 56–106%, respectively. Used on a nationwide scale (eg, for men aged 60–64 yr), long-term PSAV >0.35 versus ≤0.35 ng/ml per year appropriately reclassified 128 of 10 000 men with PCa and 8095 of 10 000 men with no PCa. Correspondingly, inappropriately reclassified were 49 of 10 000 men with PCa and 1658 of 10 000 men with no PCa. Conclusions: Long-term PSAV in addition to baseline PSA value improves classification of PCa risk and mortality. Applying long-term PSAV nationwide, the ratio of appropriately to inappropriately classified men would typically be 5:1. [Copyright &y& Elsevier]

Abstract: Background: Although 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. Objective: To determine whether clinical BPH is associated with an increased risk of PCa incidence and mortality. Design, setting, and participants: Using 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. Measurements: PCa 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 limitations: For 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. Conclusions: In 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. [Copyright &y& Elsevier]