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Prostate-specific antigen and prostate cancer: prediction, detection and monitoring

Nature Reviews Cancer volume 8, pages 268–278 (2008)Cite this article

A Corrigendum to this article was published on 01 May 2008

Key Points

  • Prostate-specific antigen (PSA) is one of the few molecular markers routinely used for detection, risk stratification and monitoring of a common cancer.

  • PSA is specific to the prostate but not to prostate cancer: benign prostate diseases often cause increases in serum PSA and most men with increased PSA do not have prostate cancer.

  • PSA strongly discriminates different cancer stages: it is higher in men with localized disease than in cancer-free controls, is associated with stage and grade in localized disease and is higher in patients with metastatic compared with localized disease.

  • Men with a higher PSA at the time of initial therapy have increased risk of recurrence.

  • PSA is a sensitive indicator of recurrence after radical prostatectomy, but far less sensitive as an indicator of recurrence after radiation therapy.

  • PSA before age 50 is a strong predictor of prostate cancer occurring up to 25 years later.

  • The introduction of PSA as a screening test has led to a sharp increase in the incidence of prostate cancer because there has been a shift to diagnosis at earlier stages and there is probably substantial 'overdiagnosis' — men diagnosed with prostate cancer whose cancer would never have affected their lives if they had not had a PSA test.

  • The effects of PSA screening on prostate cancer mortality are not yet clear.

Abstract

Testing for prostate-specific antigen (PSA) has profoundly affected the diagnosis and treatment of prostate cancer. PSA testing has enabled physicians to detect prostate tumours while they are still small, low-grade and localized. This very ability has, however, created controversy over whether we are now diagnosing and treating insignificant cancers. PSA testing has also transformed the monitoring of treatment response and detection of disease recurrence. Much current research is directed at establishing the most appropriate uses of PSA testing and at developing methods to improve on the conventional PSA test.

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Figure 1: Distribution of prostate-specific antigen (PSA) values among men of different age groups.
Figure 2: Early prediction of prostate cancer risk.
Figure 3: Three non-exclusive hypotheses to explain the association between prostate-specific antigen (PSA) level in younger men and prostate cancer diagnosed up to 25 years subsequently.
Figure 4: Prostate-specific antigen (PSA) subforms and interactions.

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Acknowledgements

We thank A. M. Cronin of Memorial Sloan–Kettering Cancer Center for compiling data on the distribution of PSA levels. We also thank J. Novak of Helix Editing for assistance with writing the manuscript. She was paid for her work by Memorial Sloan–Kettering Cancer Center.

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  1. Departments of Surgery (Urology), Clinical Laboratories, Medicine (Genitourinary-Oncology), Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, 10065, New York, USA

    Hans Lilja & Andrew J. Vickers

  2. Department of Laboratory Medicine, Lund University, University Hospital UMAS, 205 02, Malmö, Sweden

    David Ulmert

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Correspondence to Hans Lilja.

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Dr Hans Lilja is patent holder for free PSA and hK2 blood assays.

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Glossary

Stage migration

The decrease over time in the proportion of men with prostate cancer who are found to have advanced stage disease at diagnosis, commonly attributed to the introduction of PSA testing, which identifies prostate cancer at an earlier stage in the disease process.

Specificity

The number of people who test negative for a disease and who are disease-free, divided by the total number of people who are disease-free and who were tested. For a PSA test this is the proportion of men with no prostate cancer who have a low level of PSA.

Sensitivity

The number of people who test positive for a disease and who have the disease, divided by the total number of people who have disease and who were tested. For a PSA test this is the proportion of men with prostate cancer who have increased PSA.

AUC

Area under the receiver-operating characteristic curve. This value gives the probability that, in a pair of patients, one of whom had the event and the other of whom did not, the patient who had the event was given the higher risk by the predictive model.

External beam therapy

The use of radiation from a high-energy source external to the patient as a treatment for cancer.

Brachytherapy

Implantation of radioactive pellets, approximately the size of a grain of rice, into the tissue being treated for cancer.

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Lilja, H., Ulmert, D. & Vickers, A. Prostate-specific antigen and prostate cancer: prediction, detection and monitoring. Nat Rev Cancer 8, 268–278 (2008). https://doi.org/10.1038/nrc2351

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