Baseline prostate-specific antigen level and risk of prostate cancer and prostate-specific mortality: Diagnosis is dependent on the intensity of investigation

Background: When considering prostate biopsy, men and their physicians must balance the potential benefits of early diagnosis of localized cancer with the implications of overdiagnosis of clinically insignificant cancers. We investigated the risk of prostate cancer and prostate cancer-specific and all-cause mortality by baseline prostate-specific antigen (PSA) level in a population-based cohort study in Northern Ireland, where PSA screening is not recommended and where low to moderately raised (< 10.0 ng/mL) PSA levels were not routinely investigated. Methods: From a regional electronic database of PSA results, men who had their initial PSA between January 1, 1994 and December 31, 1998 were identified and followed for diagnosis of prostate cancer and prostate cancer-specific and all-cause mortality until December 31, 2003. Results: 68,354 men (mean age, 65.2 years) were included, with 50,676 (74.1%) having a baseline PSA of < 4.0 ng/mL; 402 (0.8%) of these were subsequently diagnosed with prostate cancer. PSA level was positively associated with risk of prostate cancer and prostate-specific mortality. In men with baseline PSA < 4.0 ng/mL, the rate of prostate cancer and high-grade cancer diagnosis was < 2 and < 1 cases per 1,000 person-years, respectively, whereas prostate-specific mortality was very low (0.18 cases per 1,000 person-years) compared with overall mortality (28.71 cases per 1,000 person-years). Conclusion: Following a PSA result, men need to be aware not only of the risk of prostate cancer but also of having cancer that may cause them harm during their lifetime or, more importantly, kill them. These data should inform and reassure men of their risk of clinically significant prostate cancer.