To PSA or not to PSA

By John Pickering 23/05/2012 5

As a male, 40 mumble years old, do I do it?  Do I get a prostate exam and PSA test?  Do I plan to keep doing tests every few years?

PSA (prostate specific antigen) is a blood test where elevated levels may indicate the presence of prostate cancer.  A powerful group, the US Preventative Services Task Force has come out against screening with PSA giving the test its lowest (D) grade.  They conclude “that many men are harmed as a result of prostate cancer screening and few, if any, benefit.”  Strong words. TV3 (misleadingly, but that’s another story!) and other media reported on this last night. The response of the Urological Society (at least its president) is to reject the report and urges men “not to be deterred” and to “discuss the PSA blood test with their GP.

This is approximately how my conversation went a couple of years ago.

GP: We’ll do a PSA test while we are at it.

ME:  Isn’t that a waste of time? Doesn’t it have a lot of false positives?

GP: Yes, but we can monitor for changes.

Hmmm…so it is not just the value of the test, but how it changes in time that is important.  A quick check on the internet I find that this is called the PSA “velocity.”  Interestingly in the evidence provided by the US Task Force I can find no mention of PSA velocity.

In the meantime, a quick check on the Canterbury Health Labs web site (see here) tells me that the test has a reference range of 0 to 4.0 ug/L (this is a concentration in plasma).  If a test is above this range a GP is likely to want to discuss it with you and may recommend a biopsy.

This is where life gets interesting.  A couple of weeks ago I talked of “False Positives” and introduced the diagram below.  A “False Positive” for myself would have been a PSA above 4.0 ug/L which didn’t turn out to be cancer.  The main issue with PSA tests is the high number of False Positives.  The Task Force suggested that in a screening regime after 3 or 4 tests (over several years) 12 to 13% of participants have a positive test.  Most, though, are False Positives.  Approximately 80% of Positive tests are False Positives!  Consider this – if screening happened in NZ and 500,000 men had a test every 5 years then after 15 to 20 years 500,000 * 0.12 *0.8 = 4800 men will have had a False Positive test.  Another 1200 a True Positive test.

Ideally every test result will lie in the dark blue (true negative) or dark red (true positive). In reality, there is always a few false positives and false negatives [A good test would have few (the narrow ellipse), a poor test would have many (broader ellipse)].

Importantly, the Urological Society put it this way “The PSA blood test does not diagnose prostate cancer. But it raises a red flag and identifies those men who need to have prostate cancer excluded through further investigation via a prostate biopsy.”

PSA does not diagnose – this is a very important point that a GP must communicate BEFORE a test is done.  I would be surprised if even 10% of men realize that PSA does not a diagnose.  So what happens to all the False Positives and True Positives?  This is what the Task Force focused on.

First they asked “Does PSA-Based Screening Decrease Prostate Cancer–Specific or All-Cause Mortality? Does PSA-Based Screening Decrease Prostate Cancer–Specific or All-Cause Mortality?

There was no clear evidence it does (contradictory studies).  In their useful “stats at a glance” publication they state “1 man in 1,000 – at most – avoids death from prostate cancer because of screening.”

If this is so, then it could be worth it (by the way – at a cost of $11.92 + GST + cost of GP visit – say $60 (low), then I estimate screening of 100,000 men a year would cost a minimum of $7.2M annually in NZ).

It is the next questions of the Task Force that are revealing.  The looked at the harms of screening.  The harms of those with Positive test (True or False) and then the harm to those finally diagnosed with prostate cancer.  Again the summary is revealing:

Most prostate cancers found by PSA screening are slow growing, not life threatening, and will not cause a man any harm during his lifetime. However, there is currently no way to determine which cancers are likely to threaten a man’s health and which will not. As a result, almost all men with PSA-detected prostate cancer opt to receive treatment. In addition to the frequent complications of biopsy that lead to a cancer diagnosis, there can be serious harms from treatment of screen-detected prostate cancer.

For every 1,000 men who are screened with the PSA test:

  • 30 to 40 men will develop erectile dysfunction or urinary incontinence due to treatment
  • 2 men will experience a serious cardiovascular event, such as a heart attack, due to treatment
  • 1 man will develop a serious blood clot in his leg or lungs due to treatment 

For every 3,000 men who are screened with the PSA test:

  • 1 man will die due to complications from surgical treatment

And they did not attempt to assess social or psychological harm!  Imagine the conversation at home:

Man: Hi honey, I’m home.  I got a positive PSA test today.

Woman:  That’s nice dear.  Did you get an appointment for a biopsy.

Man:  Yes, in 3 months time.

Woman: Great.  Shall we go out for dinner?

Somehow, I don’t think it would be like that, except perhaps the waiting time for a next appointment.

So where does this leave us.  My opinion, for what it is worth, is that:

  1. A PSA screening program should not take place in New Zealand.
  2. GPs should use PSA tests only where there are other risk factors
  3. Prior to any other procedure, repeat tests of positives should be done under strict conditions. Particularly the diet of the person involved should be changed to minimize the risk of false positives (there is still debate about the role of diet in false positives – so some research should be done at the same time: “Does changing diet change PSA levels in the short term?”).  Men – you can ask for this!
  4. GPs should explain that:
  •            a positive test does not mean cancer (most probably already do explain this, but it worth emphasizing),
  •            there are risks with biopsies, and
  •            there are great risks with treatment (prostectomy or radiation normally).

I qualify this with what appears to me to be a lack of assessment of the benefit of “changes in PSA” levels.  The sort of question which comes to mind is “How accurate is the diagnosis of a 2 ug/L or 100% increase (say) in PSA over 5 years?”

I wonder, would you have a PSA test?

Tagged: medical tests, prostate cancer, PSA, Risk

5 Responses to “To PSA or not to PSA”

  • Thanks for this really good summary.

    FWIW, the teaching and reading I have had on the role of PSA is that its role is to monitor the tumour load of someone who already has the diagnosis of prostate cancer, i.e. it tells us how effective treatment is.

    It’s not appropriate to use PSA as a screening tool; the morbidity and mortality that arises with investigation of false positives has huge costs to the patient, their family, and to the country as a whole.

    I would like to know why health insurance companies still use it as part of their screening despite its lack of efficacy. None I have approached have given me an answer.

    Anecdotally, my fathers’ GP used it as a screening test on him, recording 4.2. A repeat at 12 months was 9.6. Further investigation showed a high grade carcinoma that was successfully treated without any morbidity. It’s the one case I am aware of where it was useful as a “screen” and probably prevented a death.

    Despite this, would I have a PSA done on myself for screening purposes? The answer is a definite NO.

  • I went to a talk by a clinical colleague of mine today and they were talking about the risk of getting a really nasty infection through having the biopsy. Its pretty high. And all that because of a test with a really high rate of false positives? Doesn’t sound worth it.

  • Good points Stuart and Siouxsie. I’ve been thinking about why the Urologists may have come out so strongly against the report. A cynical view would be that without the test they would get fewer referrals. To be fair, though, they seem to be saying that it is “the best they’ve got.” My own research is about tests in nephrology that are also poor. The difference is that the treatment options are not (yet) doing more harm than good. It’ll be interesting to see if Medsafe make any moves to “review” the test.

  • Excellent review and sound conclusion.

    As far as I’m aware Medsafe has no control over the use of PSA tests in medical laboratories.

    The MOH essentially agreed with the Health Select Committee’s inquiry into prostate screening of otherwise healthy people which concluded; “There is no currently no evidence that shows a population based screening programme for men with no symptoms of prostate cancer would improve outcomes for men, however men who are concerned can be tested if they choose to…. Prostate cancer is an important men’s health issue and preventing deaths from prostate cancer is a high priority. However, there is no conclusive international evidence that screening for prostate cancer saves lives, nor whether the potential benefits of this testing outweighs the associated risks.

    Current international best practice is not to have a screening programme for prostate cancer. The British Association of Urological Surgeons states “Prostate cancer screening cannot be justified on current evidence. PSA testing should only be performed after full counselling. There is no evidence to support opportunistic screening”.

    There are different views even among urologists, and most urology professional bodies are clear that the evidence is still insufficient to actively encourage men to be tested…”

    Urologists clearly have a vested interest in maintaining routine testing.

  • By the way, the graphic should be rotated and raised… there are far more false positives than true positives…

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