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

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.

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).

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.

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.

Cancer causes & control : CCC. 2018 Feb 16 [Epub ahead of print]

Rebecca Gilbert, Kate Tilling, Richard M Martin, J Athene Lane, Michael Davis, Freddie C Hamdy, David E Neal, Jenny L Donovan, Chris Metcalfe

Population Health Sciences, Bristol Medical School, University of Bristol, 39 Whatley Road, Bristol, BS8 2PS, UK. ., Population Health Sciences, Bristol Medical School, University of Bristol, 39 Whatley Road, Bristol, BS8 2PS, UK., Nuffield Department of Surgical Sciences, University of Oxford, John Radcliffe Hospital, Headington, Oxford, OX3 9DU, UK., Department of Oncology, University of Cambridge, Addenbrook's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.


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