Elevated Prostate-Specific Antigen Levels Up to 25 Years Prior to Death from Prostate Cancer

Abstract

Abstract Objective: We tested the hypothesis that prostate-specific antigen (PSA) levels would be higher among prostate cancer deaths as compared with controls over time in the 25-year follow-up of the Multiple Risk Factor Intervention Trial of participants ages 35–57 at entry. Methods: The initial stored serum samples were collected in 1973–1975 and the mean length of follow-up to prostate cancer death was 17 years. Results: There were 63 prostate cancer deaths and 63 controls matched by age, clinical site, and length of follow-up. The mean PSA level for prostate cancer decedents was 2.84 ng/ml as compared with 1.10 ng/ml for controls (P = 0.002 for difference). There were nine men who died from prostate cancer and no controls with PSA levels > 4 ng/ml. Risk of prostate cancer death increased with increasing PSA levels, with increased risk observed even at moderate levels of PSA. Many of those with high PSA levels in 1973–1975 died from prostate cancer many years after the elevated PSA. Conclusion: PSA levels measured from blood obtained before the introduction of widespread PSA testing were a strong predictor of prostate cancer death over 25 years of follow-up. Studies of prostate cancer etiology and chemoprevention need to focus on middle-aged or younger men with longer follow-up.