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Early detection of prostate cancer: myth or magic?

Sandy Tyndale-Biscoe
Chairman
Prostate Cancer Support Federation

In its early stages, prostate cancer does not normally have any symptoms. So what should we do if the only means of early detection is a controversial and flawed test? Such a test is the prostate specific antigen (PSA) test, and clinicians and patients are deeply divided on its use ...

Prostate specific antigen (PSA) is a protein, the purpose of which is to liquify semen. It is produced in large quantities in a man's prostate, which is where most of it should stay, except during ejaculation. However, a small, but quite variable quantity is normally found in the bloodstream, and this frequently increases with age. The PSA test, a simple and cheap blood test, measures the serum level of PSA.

Where there is prostate disease, the PSA serum level is often elevated. In particular, an active advanced prostate cancer will almost invariably result in a high PSA reading. But the extent to which it does so in early stage prostate cancer is very variable. As a result, there is often no cut-off level at which a clinician could confidently state whether cancer is present or not.

A reliable indicator?
In short, a single PSA test can be a poor test for prostate cancer; it produces many false positives, and sometimes fails to detect lethal cancers. It can, however, act as an indicator of possible prostate disease, of which prostate cancer is the most life threatening. It is claimed that a very high proportion of PSA-detected cancers are harmless and will never cause any problems. Unfortunately, distinguishing these from the more serious cases is, currently, very difficult. Nonetheless, in countries where PSA testing of symptomless men is commonplace (ie, not in the UK), mortality from the disease has declined significantly, and many believe that this fact is attributable to earlier diagnosis after PSA testing.

Many clinicians argue that, for all its limitations, it's still the o
only test that might indicate early stage (curable) prostate cancer, and that, when taken into consideration with other key factors, such as ethnicity, family history of the disease and PSA history ("What was it last year?" would be the first question anyone would ask when faced with a suspicious reading), a PSA test result, or better still a PSA history, is a vital early diagnosis tool.

The Great PSA Debate
Clinicians are divided on the issue of PSA testing, and by no means all of them are in favour. At a meeting of the British Prostate Group a couple of years ago, a majority of clinicians present said that they would not themselves have a PSA test.

In this they were making a personal decision: avoiding the high risk of unnecessary treatment and its attendant side-effects, particularly sexual dysfunction, is, to them, worth the penalty of a small increase in risk of dying of the disease through late diagnosis. This is a sophisticated decision, probably beyond the capability of most laymen. It is also predicated on the view that over-treatment is somehow inevitable. Research is beginning to show that this need not be the case.

Earlier this month, at an event known as The Great PSA Debate, nearly 100 representatives of patient groups, all members of the Prostate Cancer Support Federation, joined with a panel of six experts from both sides of the argument, representing clinicians, charities and patients to debate the issues. In a breakthrough moment, unanimity was achieved and all present, with one abstention, voted for a motion that all men at risk should be made aware of the PSA test, its benefits and limitations, and their right to have it.

So what should you say to a man who, having no symptoms, asks for a PSA test? The government initiative, the Prostate Cancer Risk Management Programme (PCRMP), states that all men over 50 are entitled to the test, having been fully informed about it. But the guidance offered is based on old evidence, it is lengthy, complex, and it does not reflect current clinical practice. The Prostate Cancer Support Federation, supported by Prostate UK, the UK's largest prostate charity, have produced a simple leaflet entitled the "real" PCRMP (available from www.pcrmp.org.uk). Its key points are summarised below:

  • The PSA test is a blood test used to help detect prostate cancer. In its early stages, prostate cancer generally produces no symptoms, so it is important to diagnose the disease before any symptoms arise and while it is still potentially curable. Recent results of a major European trial suggest that treating prostate cancer may significantly prolong a man's life.1
  • A high level of PSA is likely to be an indication of prostate cancer and should, therefore, prompt further investigation.
  • A moderately raised PSA means that other factors, including digital rectal examination, ethnicity, family history, prostate volume, PSA history, and free-to-total PSA ratio, should be considered in determining whether to send a man for further tests such as biopsy.
  • However, in three-quarters of such cases, further tests do not detect cancer. There can be other reasons for a moderately elevated PSA (eg, urinary infection and enlarged prostate) and these may need treatment.
  • Prostate cancer is not always aggressive or life threatening and a clinician may not be able to tell whether the condition, once diagnosed, is life-threatening or harmless.
  • A low level of PSA does not guarantee the absence of prostate cancer. This is because localised prostate cancer does not always produce a raised level of PSA.
  • The uncertainties may be reduced by men having an annual test. Regular monitoring can highlight any significant or gradual increase, so that even when the PSA is within the "normal" range, one may be alerted to the need for further investigation.

Reference
1. Schröder FH, Hugosson J, Roobol MJ et al. Screening and prostate-cancer mortality in a randomized European study. New Engl J Med 2009;360:1320-8.

Resources
Prostate Cancer Support Federation
W: www.prostatecancerfederation.org.uk

Prostate UK
W: www.prostateuk.org

"Real" PCRMP
W: www.pcrmp.org.uk