Objective: To determine the longitudinal changes of benign prostate-specific antigen (BPSA) and [-2]proPSA and how these changes relate to the outcomes. These markers have been shown to be predictive of prostate cancer (CaP) and benign prostatic hyperplasia treatment; however, little is known about longitudinal changes in these markers. Methods: In 1990, a 25% subsample from a cohort of white men aged 40-79 years, who were randomly selected from Olmsted County, Minnesota residents, completed a detailed clinical examination. BPSA and [-2]proPSA were measured from frozen sera. The men were evaluated biennially (median follow-up 7 years; range 0-8.8). Mixed-effects regression models were used to estimate the longitudinal changes in the BPSA and [-2]proPSA levels overall and by outcomes. Spearman correlations were used to compare these changes with the baseline levels and the annualized changes in urologic measures. Results: The median and 25th and 75th percentiles annualized percent change for [-2]proPSA and BPSA was 3.7%, 2.5% and 5.2% and 7.3%, 6.8%, and 7.7%, respectively. The annualized percent change for both markers correlated with the baseline and annualized changes in PSA and prostate volume. The annualized percent change increased with increasing age decade for [-2]proPSA but not for BPSA. The rate of increase in [-2]proPSA was significantly greater for men who developed enlarged prostates (median 3.5%, 25th and 75th percentile 2.6% and 4.4%, respectively) or CaP (median 8.1%, 25th and 75th percentile 6.6% and 9.8%, respectively) compared with those who did not develop enlarged prostates (median 1.9%, 25th and 75th percentile 0.9% and 3.0%, respectively) or CaP (median 3.5%, 25th and 75th percentile 2.3% and 4.8%, respectively). Conclusion: BPSA and [-2]proPSA levels increase over time. The annualized percent change in [-2]proPSA increases with age and might be a useful predictor of CaP development.
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