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

Becky Gilbert, Kate Tilling, Richard Martin, J. Athene Lane, Michael Davis, Freddie Hamdy, David E Neal, Jenny Donovan, Chris Metcalfe

Research output: Contribution to journalArticle (Academic Journal)peer-review

12 Citations (Scopus)
560 Downloads (Pure)


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.
Original languageEnglish
Number of pages6
JournalCancer Causes and Control
Early online date16 Feb 2018
Publication statusE-pub ahead of print - 16 Feb 2018

Structured keywords

  • BTC (Bristol Trials Centre)
  • BRTC
  • Centre for Surgical Research


  • Prostate cancer
  • Prostate-specific antigen testing
  • Biopsy
  • Age
  • Reference ranges


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