Abstract
PurposeTo examine whether age-related reference ranges for “normal” prostate-specific antigen (PSA) change (determined in men without prostate cancer) can be used to identify men at high risk of having prostate cancer.MethodsSubjects were men aged 50–69 years with PSA < 10 ng/mL from the UK-based Prostate Testing for cancer and Treatment (ProtecT) study. Men with prostate cancer were categorized as high or low risk of progression (Low risk: Gleason score ≤ 6 and stage T1–T2a; High risk: Gleason score 7–10 or stage T2C). Men without prostate cancer were those with no histological confirmation of prostate cancer. Previously developed longitudinal reference ranges for normal age-related PSA change were used to calculate an age-specific PSA threshold. We compared the ability of our age-specific PSA threshold to discriminate between high- and no/low-risk prostate cancer with that of two existing thresholds: (i) threshold of PSA = 3 ng/ml for all ages; (ii) National Institute of Clinical Excellence (NICE) guidelines dependent on age-group thresholds (age 50–59: PSA = 3 ng/mL; age 60–70: PSA = 4 ng/mL; age ≥ 70: PSA = 5 ng/mL).ResultsWe included 823 men with high-risk prostate cancer and 80,721 men with no/low-risk prostate cancer. A threshold of PSA = 3 ng/ml for all ages identified more high-risk prostate cancers, recommending biopsy in 9.8% of men, of which 10.3% (n = 823) had high-risk prostate cancer. Using the NICE guidelines as the threshold for biopsy, 6.9% men were recommended for biopsy, of which 11.9% (n = 668) had high-risk prostate cancer. Using the new age-specific threshold for biopsy, 2.3% men were recommended for biopsy, of which 15.2% (n = 290) had high-risk prostate cancer. The age-specific threshold identified fewer high-risk prostate cancers, but fewer men received unnecessary biopsy.ConclusionThere is no benefit to using reference ranges for “normal” PSA that change with age nor the age-specific thresholds suggested by the NICE guidelines. While the age-varying thresholds are more discriminatory, too many high-risk cancers are missed.
Highlights
Prostate-specific antigen (PSA) testing, followed by biopsy if the PSA level is raised, is a widely accepted screening method for prostate cancer [1]
There were 81,553 men aged ≥ 50 years with at least one PSA result and PSA ≤ 10 ng/mL. 9 men were dropped from analysis as their clinical information was missing
There were no substantial differences in baseline characteristics between men with high-risk prostate cancer and no/ low-risk prostate cancer other than mean age (62.4 years vs. 59.3 years, p ≤ 0.001) and mean PSA level (5.5 vs. 1.3 ng/ mL, p ≤ 0.001) (Table S1)
Summary
Prostate-specific antigen (PSA) testing, followed by biopsy if the PSA level is raised (typically ≥ PSA 3–4 ng/mL), is a widely accepted screening method for prostate cancer [1]. PSA levels increase with age, and the natural variability in PSA level (both within men over time, and between men) is likely to be greater in older men [5], obscuring disease-related changes. Current age-related PSA thresholds are based on cross-sectional data and do not attempt to distinguish these different sources of variability, nor to describe serial changes in PSA level for aging individuals
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