More harm than good: rethinking routine prostate cancer screening

My offer for a public debate was accepted after I co-published opposing viewpoints about the high rates of over-diagnosis and over-treatment of early stage prostate cancer with leading urologist Professor Tony Costello in a Melbourne newspaper last year. The debate took place at a Melbourne conference…

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A diagnosis of early prostate cancer may end up doing more harm than good. Medical Office picture from Shutterstock

My offer for a public debate was accepted after I co-published opposing viewpoints about the high rates of over-diagnosis and over-treatment of early stage prostate cancer with leading urologist Professor Tony Costello in a Melbourne newspaper last year.

The debate took place at a Melbourne conference on prostate cancer last week. It received wide coverage in newspapers – here, here and here, television radio, and online. All of this is useful and important because it helps stimulate the very important debate about widespread PSA screening.

Prostate specific antigen (PSA) is an enzyme secreted in large amounts by normal as well as cancerous prostate cells. Only small amounts of PSA leak into circulation from a normal prostate, but this increases with any prostatic disease, benign or malignant.

PSA concentration is expressed as a number and its discovery in 1983 led to it being used as a screening blood test for early prostate cancer. A level below four is considered normal and men with abnormal results are usually sent for biopsies. It has been widely performed in Australian men for over ten years as part of a general health check but its ability to save lives is now being assessed and tested.

Ideal health

For years now, family physicians, the Urological Society of Australia and New Zealand and spokespeople for treatment advocacy groups, such as the Prostate Cancer Foundation of Australia have been telling men to have blood tests with a PSA as part of their regular health check up because early diagnosis may save their life.

The constant message is that men need to look closely for any signs of early prostate cancer by having a PSA and a digital rectal examination. This is because, up until recently, our belief and practice was that if the PSA was high, the patient should be referred to a urologist for a transrectal biopsy (a large and very unpleasant needle, inserted under local anaesthetic through the wall of the rectum up to 24 times, just above the anus). And if this biopsy showed prostate cancer, the man would usually be offered immediate radical treatment with surgery or radiation to cure the cancer.

But we’ve long known that prostate cancer is a disease that men can harbour for most of their lives without knowing. It is very commonly found during postmortem (even in very young men). We also now know that PSA is highly unreliable as a predictor of cancer.

False results and consequences

A major prospective prostate cancer trial actually found cancer in 15% of men with normal direct rectal examination results and PSA of less than the “normal” concentration of four (considered as the cut-off between “normal” and “abnormal”). It also found cancer in 25% of the participants with levels between three and four. This is similar to the rate of 25% of biopsies showing prostate cancers in men with so-called abnormal PSA. So you have an almost equal chance of having cancer found irrespective if your PSA is normal or abnormal!

Indeed, the false-positive and false-negative rates of PSA alone make it a useless screening test. Our current rate of PSA testing uptake threatens to diagnose up to 60,000 men a year in Australia, 25 times the number destined to die from it.

Prostate cancer appears to be two diseases, an uncommon one that can kill you (at an average age of 81 years) and a very common one that poses no risks. Even though prostate cancer is a leading cause of male mortality in Australia (with over 2000 deaths a year), it’s never been known whether radical treatment of early stage disease can alter the natural history of those cancers biologically destined to kill the patient or whether it only “cures" those cancers destined to remain indolent for many decades and not affect lifespan.

Man should be asked to provide informed consent for PSA tests. Man choosing his way from www.shutterstock.com

Some believe that the term “early stage prostate cancer” is misleading and a misnomer for most men, similar to the condition called chronic lymphocytic leukaemia, which sounds frightening but is usually a very indolent disease that lies dormant for decades and rarely ever needs treatment.

All harm, no help?

Recent evidence from several high-quality prospectively randomised clinical trials have shown two stunning results. The first two (here and here) showed that regular screening with PSA and treatment of detected cancers produces no overall survival benefit for the treated group, and only a tiny reduction in deaths due to prostate cancer. The third showed that radical treatment with surgery or radiation therapy provides no benefit for the vast majority of men who have been treated this way and causes very serious and long-lasting side-effects.

PSA screening of the male Australian population probably doesn’t save any lives at all, but leads to a lot of over-diagnosis of a condition called early prostate cancer that will not shorten the lives of the overwhelming majority of men. This creates serious harms, including toxicities from unnecessary and radical treatments and imposes vast financial and manpower costs on our health system.

The harms come from the transrectal biopsies (pain, infection and haemorrhage), and initial radical treatments. Then, there are penile implants and drugs to treat sexual impotence resulting from treatment and the cost of urethral sphincters (around $20,000 for every initial insertion and then replacement). Add to this the time of physiotherapists and nurses for urinary incontinence and the psychologists for the depression and associated relationship stresses.

Time to change

Following an extensive and detailed review of all the literature, an expert team from the US Preventative Services Taskforce has very recently issued the lowest possible recommendation for PSA screening because it’s highly likely that its harms significantly outweigh its benefits. And the test has been called a public health disaster by Dr Richard Ablin, who invented it. I clearly concur with him.

It’s time for family physicians to stop doing routine screening PSA tests of Australian men unless patients decide to proceed after being told about the latest research and indicate they understand the potential benefits and harms. Indeed, they should be asked to provide informed consent.

For those diagnosed with early prostate cancer, immediate and radical treatment is unnecessary for the vast majority and active surveillance or watchful waiting should be recommended. It’s now reasonable and preferable that all men be offered a second opinion before proceeding to radical treatment for early stage prostate cancer.

As with all advances in medical treatment over the last 350 years, we depend on constant clinical research comparing what we currently do with what we hope may be better by some measurable parameter. When the evidence changes, we must all revise our beliefs and practices.


Read the case for PSA testing

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28 Comments sorted by

  1. John Coochey

    Mr

    I have a couple of issues with this paper for example

    "it’s never been known whether radical treatment of early stage disease can alter the natural history of those cancers biologically destined to kill the patient"...
    "and only a tiny reduction in deaths due to prostate cancer."

    Surely if cancer is removed before it can spread then that must stop the patient dying from that particular cancer. The last time I saw figure saying there was no increase in life expectancy from surgery the study was shot down by its own data which actually showed and increased life expectancy but it was not huge, about eight and a half months from memory so fairly low compared with many other interventions but nevertheless it was there. There always seems to be arguments put forward for radical surgery but these never seem to be made against TURP's for treating BPH which is not life threatening.

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    1. Chris O'Neill

      Telecommunications Engineer

      In reply to John Coochey

      "Surely if cancer is removed before it can spread then that must stop the patient dying from that particular cancer."

      Well, no. That's what I thought until I was told that PSA tests continue after Prostatectomy even if the cancer was organ-confined. The problem is that Prostate cells escape into the rest of the body from very, very early (perhaps before there's any cancer as well as after). So if the cancer is dangerous then most probably it has already escaped and it's too late to avoid its effects…

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    2. John Coochey

      Mr

      In reply to Chris O'Neill

      Well actually that is stretching a long bow, even if cancer cells have escaped that is what we have chemo for, otherwise you are saying that treatment is worthless once cancer is detected. One issue not yet examined is why we have a double standard on screening (my wife is being treated for breast cancer which appeared three weeks after a negative test) especially for cervical cancer where testing was originally every year even for women who had never been sexually active, epidemiology recommended every three years and so we have a compromise of every two years despite a inoculation being available. I believe in the Netherlands testing only takes place for sexually active women over the age of 28. Your point about pre emptive removal raises the issue of side effects.

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    3. Michael Macdonald

      Chemist

      In reply to John Coochey

      The 'inoculation' only prevents cervical cancer of viral cause, not all cervical cancers are caused by viruses.

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    4. Chris O'Neill

      Telecommunications Engineer

      In reply to John Coochey

      "Well actually that is stretching a long bow"

      OK, try telling that to your urologist.

      "even if cancer cells have escaped that is what we have chemo for"

      Assuming it works.

      "otherwise you are saying that treatment is worthless once cancer is detected"

      That's what this article is about (but there's no dispute about more advanced cancer).

      "One issue not yet examined is why we have a double standard on screening"

      Cancers ain't cancers. Different cancers have different risks of causing…

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    5. John Coochey

      Mr

      In reply to Michael Macdonald

      And how much cervical cancer is non viral? The double standard on screening does exist because I remember when working for an independent MHR and had a letter published pointing out the epidemiology of breast cancer screening for women under forty and the very high cost of screening in Australia compared with the UK the switch board lit up like a Christmas tree with calls from everything short of the Minister's office. There was an empire under threat, if they had been sanguine about the issue a simple letter in reply would have sufficed.

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    6. John Coochey

      Mr

      In reply to Michael Macdonald

      Then the cost per QALY is obviously high for indiscriminate screening

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  2. William Ferguson

    Software Developer

    It's interesting contrasting this article with the one that is for PSA screening.

    This one contains a large amount of emotive and inflammatory language (eg 7 instances of "radical treatment"). While the other is concise and clear.

    If I didn't know better it almost seems like this author has attempted to sabotage his own position.

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    1. Michael Macdonald

      Chemist

      In reply to William Ferguson

      The term 'radical treatment' usually refers to the total removal of the prostate or other organ e.g. radical mastectomy. I assume this is what the author was referring to when they repeated 'radical treatment' throughout the essay.

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    2. Chris O'Neill

      Telecommunications Engineer

      In reply to Michael Macdonald

      "The term 'radical treatment' usually refers to the total removal of the prostate or other organ"

      Yes, it always does. "Radical" is the normal technical term for completely removing an organ.

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  3. Jon Hunt

    Medical Practitioner

    As a GP I have the difficulty of explaining all of the above to male patients sufficiently that they can understand it. I doubt that many do because I'm not even sure that I do. My feeling is that they ask for the test because it is a "test for prostate cancer".

    The test has also been used what I would say is a flippant manner in that many of my patients have had yearly PSAs by another GP, I then have to convince them that this may not be the correct thing to do without considering the ramifications. Or they may know someone whose cancer was picked up "early" because they had their PSA done.

    There is also the legal issues of failure to diagnose which I understand is starting to rear its head..

    All in all, I think it is more likely than not to be a stupid test and for simplification I would not complain if it were to be banned..

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    1. Chris O'Neill

      Telecommunications Engineer

      In reply to Jon Hunt

      "As a GP I have the difficulty of explaining all of the above to male patients sufficiently that they can understand it."

      I'm not a GP of course but I'd say the responsibility for explaining the above should rest with the Urologist that the patient is referred to on the basis of the PSA test.

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    2. Sue Ieraci

      Public hospital clinician

      In reply to Chris O'Neill

      But that misses Jon Hunt's point - he needs to have the discussion with his patient about WHETHER to do the test in the first place.

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    3. Chris O'Neill

      Telecommunications Engineer

      In reply to Sue Ieraci

      Yes you're right but my view is that the ultimate problem is over-treatment rather than over-testing so on that basis I don't have much of a problem with doing useless tests. It's nothing more than a waste of taxpayers' money to me. Whether something is a waste of taxpayers' money or not is not something that a GP needs to discuss with his patient.

      Over-treatment is a far more serious issue, and that issue arises in the context of patient and his urologist.

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    4. Paul Rogers

      logged in via Twitter

      In reply to Chris O'Neill

      If a PSA test saves a life, I can't see that it is a "useless test". Are you claiming that the PSA test has never saved a life -- or many?

      Over-treatment is another issue, and essentially unrelated to the debate about the fundamental utility of the PSA test.

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    5. Chris O'Neill

      Telecommunications Engineer

      In reply to Paul Rogers

      "If a PSA test saves a life"

      It doesn't save lives compared with giving Prostatectomies to the same number of randomly selected 45 year old men. Doesn't that satisfy the definition of useless?

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    6. Paul Rogers

      logged in via Twitter

      In reply to Chris O'Neill

      Of course not, because you have ignored the cultural and social imperatives. that make random prostatectomies impossible. And you would also have to account for the substantial morbidities from such surgery.

      Would you apply the same premise of random mastectomies for 45 year old women with BRCA1/2 mutation? How about random heart bypasses at 45 compared to LDL screens and statins?

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    7. Chris O'Neill

      Telecommunications Engineer

      In reply to Paul Rogers

      "Of course not, because you have ignored the cultural and social imperatives."

      You're dodging the issue. Just because cultural and social imperatives make random Prostatectomies for 45 year olds impossible does not mean that the current strategy is any better.

      "you would also have to account for the substantial morbidities from such surgery."

      The only reason for making that statement is the implication that morbidity of the current strategy is somehow better. That hardly seems likely.

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    8. Paul Rogers

      logged in via Twitter

      In reply to Chris O'Neill

      "The only reason for making that statement is the implication that morbidity of the current strategy is somehow better. That hardly seems likely."

      Well, of course! The putative incidence of morbidity from surgery in any PSA screening strategy would be demonstrably lower that what it would be if random prostatectomies were performed.

      In a cohesive risk management strategy that includes PSA testing, invasive approaches are not mandatory.

      BTW, your argument sets up a 'straw man' because the comparison should not reference PSA screens per se in the current 'over-treatment' scenario, but PSA as a valid and useful element of a risk assessment.

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    9. Chris O'Neill

      Telecommunications Engineer

      In reply to Paul Rogers

      "The putative incidence of morbidity from surgery in any PSA screening strategy would be demonstrably lower that what it would be if random prostatectomies were performed."

      How so? Is there something special existing Prostatectomies that makes them less likely to cause morbidity?

      "In a cohesive risk management strategy that includes PSA testing, invasive approaches are not mandatory.

      BTW, your argument sets up a 'straw man'"

      The irony. As I pointed out in the other article:

      Current strategy: 48 treatments per life saved.

      "Unachievable" or whatever you want to call it strategy: 23 treatments per life saved (deaths from Prostate cancer in 2010 were 4.4% of the total).

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    10. Chris O'Neill

      Telecommunications Engineer

      In reply to Sue Ieraci

      Sue Ieraci:

      "But that misses Jon Hunt's point - he needs to have the discussion with his patient about WHETHER to do the test in the first place."

      That's also correct from the point of view that once you're shipped off to the urologist, the advice you receive is somewhat biassed.

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  4. Chris O'Neill

    Telecommunications Engineer

    The Age-standardised death rate from Prostate Cancer in Australia was 15.7 per 100,000 men in 1982 and 14.1 per 100,000 in 2005. this was in spite of the rate of diagnosis more than doubling from 1993 onwards. So we knew a while ago that the treatments weren't having much effect.

    Some argue that the treatment success rate is much greater then it used to be but that's simply because far more asymptomatic cases are detected now which are nearly always not dangerous.

    There has been obviously excessive…

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  5. John Holmes

    Agronomist - semi retired consultant

    Having had a high PSA for some time, which over the last 3-4 years is slowly declining, and having been subjected to 2 biopsies due to this with so far no diagnosis of cancer, I would concur with others that as a patient this is not a good experience. The last biopsy resulted in a massive urinary track infection (passing barb wire!) the only benefit to me was the loss of 10% of my body weight which has assisted in managing my type 2 diabetes. Now that the frequency of antibiotic resistant bugs is rapidly increasing, I would suggest that these procedures have the potential to cause more problems than the disease its self.

    Is there any interaction with the causes of Type 2 Diabetes or as a result of having such a problem and the high PSA's?

    Do not mind the need to have a check up every 12 months, but when the tests can nearly kill you, not so good.

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  6. Paul Rogers

    logged in via Twitter

    What would you suggest we do: wait until we start peeing blood?

    After 20 years of PSA tests, I'll make up my own mind how to handle this (with the advice of my doctor of course ;-).

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    1. Chris O'Neill

      Telecommunications Engineer

      In reply to Paul Rogers

      "What would you suggest we do?"

      Given that the PSA test is not significantly better than rolling a dice, if you really want to do something useful then get your prostate removed without bothering with any tests.

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  7. Roger Peters

    Psychologist

    I thought that the article by Arkes H, et al (2012) Psychological Research and Prostate Cancer screen controversy in Psychological Science last month (23(6) 547-553, was particularly useful and for me slam dunked the argument against. By the way I will not be trying to convince "survivors", it becomes a very emotive issue for so many and I want to stay friends.

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    1. Chris O'Neill

      Telecommunications Engineer

      In reply to Roger Peters

      "By the way I will not be trying to convince "survivors""

      The first thing to realize is that the vast majority (probably > 80%) would have survived without doing anything anyway (or die from something else). Even that fact seems to often be ignored.

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