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Developing new age-specific prostate-specific antigen thresholds for testing for prostate cancer.

ABSTRACT: PURPOSE:To 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. METHODS:Subjects 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). RESULTS:We 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. CONCLUSION:There 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.

SUBMITTER: Gilbert R

PROVIDER: S-EPMC5834577 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Developing new age-specific prostate-specific antigen thresholds for testing for prostate cancer.

Gilbert Rebecca R Tilling Kate K Martin Richard M RM Lane J Athene JA Davis Michael M Hamdy Freddie C FC Neal David E DE Donovan Jenny L JL Metcalfe Chris C

Cancer causes & control : CCC 20180216 3

<h4>Purpose</h4>To 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.<h4>Methods</h4>Subjects 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; H ...[more]

PMID: 29453511

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Project description:After the introduction of the prostate specific antigen (PSA) test in the 1980s, a sharp increase in the incidence rate of prostate cancer was seen in the United States. The age-specific incidence patterns exhibited remarkable shifts to younger ages, and declining rates were observed at old ages. Similar trends were seen in Norway. We investigate whether these features could, in combination with PSA testing, be explained by a varying degree of susceptibility to prostate cancer in the populations. We analyzed incidence data from the United States' Surveillance, Epidemiology, and End Results program for 1973-2010, comprising 511,027 prostate cancers in men ≥40 years old, and Norwegian national incidence data for 1953-2011, comprising 113,837 prostate cancers in men ≥50 years old. We developed a frailty model where only a proportion of the population could develop prostate cancer, and where the increased risk of diagnosis due to the massive use of PSA testing was modelled by encompassing this heterogeneity in risk. The frailty model fits the observed data well, and captures the changing age-specific incidence patterns across birth cohorts. The susceptible proportion of men is [Formula: see text] in the United States and [Formula: see text] in Norway. Cumulative incidence rates at old age are unchanged across birth cohort exposed to PSA testing at younger and younger ages. The peaking cohort-specific age-incidence curves of prostate cancer may be explained by the underlying heterogeneity in prostate cancer risk. The introduction of the PSA test has led to a larger number of diagnosed men. However, no more cases are being diagnosed in total in birth cohorts exposed to the PSA era at younger and younger ages, even though they are diagnosed at younger ages. Together with the earlier peak in the age-incidence curves for younger cohorts, and the strong familial association of the cancer, this constitutes convincing evidence that the PSA test has led to a higher proportion, and an earlier timing, of diagnoses in a limited pool of susceptible individuals.

Dataset Information

Developing new age-specific prostate-specific antigen thresholds for testing for prostate cancer.

Publications

Developing new age-specific prostate-specific antigen thresholds for testing for prostate cancer.

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