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PSA screening and prostate cancer over-diagnosis

OVER-DIAGNOSIS EPIDEMIC – We finish our first week of this series with Robert Burton, Christopher Stevenson and Mark Frydenberg examining prostate cancer screening. Scientific oncology started with the…

To prevent one death from prostate cancer, 1,055 men would need to be screened and 37 cancers detected. Isaac Leedom

OVER-DIAGNOSIS EPIDEMIC – We finish our first week of this series with Robert Burton, Christopher Stevenson and Mark Frydenberg examining prostate cancer screening.

Scientific oncology started with the creation of the modern microscope, which provided the basis for the modern pathologic study of cancer in the late 19th century, and established the “fatal cancer” myth. As one researcher arguing against breast cancer screening put it, “since then, without pause for thought, the microscopic identification of cancer according to the classic criteria has been associated with the assumed prognosis of a fatal disease if left untreated.”

Earlier this week, an article in this series looked at the adverse effects of breast cancer screening. Today, we will examine the role of screening in the over-diagnosis of prostate cancer.

The fatal cancer myth began to unravel a century later. A 1993 study for instance, noted that prostate cancer was unique because “the frequency of histologically (pathologically) confirmed invasive cancer at autopsy greatly exceeds the prevalence of clinically significant carcinoma during life.”

The authors then affirmed that in no other malignancy was there such a vast reservoir of undetected cases that may never be clinically significant or cause death. They also noted that up to 40% of all men might be treated for prostate cancer but only 8% would ever have a cancer large enough to be diagnosed and only 3% would die of it.

Over-diagnosis of cancer is the detection of asymptomatic cancers that will not become clinically significant and cause disease or death in the patient’s lifetime. How many men have prostate cancer that might never come to light without screening and are therefore at risk of over-diagnosis?

High prevalence

A 2010 review of a 1996 study found that microscopic asymptomatic prostate cancers had been detected in 525 men of various ages killed in motor vehicle accidents in the United States (U.S). The findings indicated that this type of cancer could affect approximately a third of American men aged 30 to 39 years, increasing to about 70% at age 70 to 79 years.

Looking at these figures, together with similar autopsy studies, the authors of the review concluded prostate cancer was likely detectable in between 30 to 70% of men over 60 years old.

And a 2009 Australian study of prostate tissue, sampled from 133 cadavers referred for coronial autopsy, found invasive prostate cancer in about a quarter of the 70 men aged 50 or more years.

It seems over-diagnosis of prostate cancer was already inevitable by the time the Prostate Specific Antigen (PSA) blood test was introduced for prostate cancer screening in Australia in the late 1980s, because it could detect cancers that had previously gone undiagnosed.

Since PSA testing began in the late 1980s, over 75,000 Australian men may have been turned into prostate cancer patients, possibly for only a small benefit. Alex E Proimos

Winds of change

In July 2012, the U.S. Preventive Services Task Force (USPSTF) found that “The mortality benefits of PSA-based prostate cancer screening through 11 years are, at best, small and potentially none, and the harms are moderate to substantial”. The task force recommended against PSA-based screening for prostate cancer, stating that the recommendation applied to men in the general U.S. population, regardless of age.

The recommendation was based on an analysis of the evidence from trials of PSA screening in the U.S. and Europe, but mainly on the 2009 report of the European randomised controlled trial (RCT), where 182,000 men aged 50 to 74 years from seven European countries were randomised to either PSA testing every two to seven years or to usual care.

This report was updated in 2012 with an average follow-up of 11 years. It found a statistically significant reduction (21%) in prostate cancer mortality in the population of men invited to screen and a 29% reduction in those who were actually screened.

But this reduction in mortality came at a cost. The authors reported that to prevent one death from prostate cancer at 11 years follow-up, 1,055 men would need to be invited for screening and 37 cancers would need to be detected. The USPSTF also noted that there was convincing evidence PSA-based screening led to substantial over-diagnosis of prostate tumours.

Unknown quantity

The amount of over-diagnosis of prostate cancer is an important concern because men with cancers that would remain asymptomatic for the remainder of their lives cannot benefit from screening or treatment.

Based on our analysis of trends in prostate cancer incidence (new cases per year) since PSA testing began in the late 1980s, over 75,000 Australian men who might never have known they had prostate cancer may have been turned into prostate cancer patients, possibly for only a small benefit.

At the same time, the men were exposed to the potential harms (incontinence, impotence) of unnecessary treatment. These harms can be avoided if the prostate biopsy shows that they have low-risk disease and are then managed by active surveillance, rather than immediate treatment of their cancer.

Deaths from prostate cancer have fallen by approximately 13,000 during that same time. Some men can be saved by early detection and treatment but others clearly do not benefit.

Performing PSA tests on everyone leads to substantial over-diagnosis. But not performing PSA tests at all would inevitably lead to under-diagnosis of some men who may have been cured by early detection and treatment. Before consenting to undergo PSA screening, men should understand that while there are possible, if modest, benefits to getting tested, they may be exposed to substantial harms from over-diagnosis and over-treatment.

Have you or someone you know been over-diagnosed? To share your story, email the series editor.

This is part five of our series on over-diagnosis, click on the links below to read other articles:

Part one: Preventing over-diagnosis: how to stop harming the healthy

Part two: Over-diagnosis and breast cancer screening: a case study

Part three: The perils of pre-diseases: forgetfulness, mild cognitive impairment and pre-dementia

Part four: How genetic testing is swelling the ranks of the ‘worried well’

Part six: Over-diagnosis: the view from inside primary care

Part seven: Moving the diagnostic goalposts: medicalising ADHD

Part eight: The ethics of over-diagnosis: risk and responsibility in medicine

Part nine: Ending over-diagnosis: how to help without harming

Join the conversation

47 Comments sorted by

  1. Paul Rogers

    logged in via Twitter

    "Before consenting to undergo PSA screening, men should understand that while there are possible, if modest, benefits to getting tested, they may be exposed to substantial harms from over-diagnosis and over-treatment."

    "Modest?" Spoken like a public health professional and not a personal physician. I would hardly call saving someone's life a modest benefit.

    I've no disagreement with the message about over-treatment and the consequences. However, perhaps you could also have a series on where PSA testing has saved lives, rather than resulted in over-diagnosis. You know, for balance . . .

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    1. Wendy Watson

      logged in via Facebook

      In reply to Paul Rogers

      I agree Paul,
      'Save your life' does not seem to me to be a modest benefit!

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    2. Rod Govers

      Retired IT administrator

      In reply to Paul Rogers

      As one who was diagnosed at 50 with PCa followed by a radical prostatectomy then 6 years later 30 radiation treatments when my PSA began to rise again, I have no regrets about that initial PSA test. My PSA is rising again and hormone treatment is indicated sometime in the future.

      The PSA test and digital exam are NOT the tests which lead to treatment. The PSA test really is a marker that can lead to other tests. My high PSA was followed up with a digital exam which found lumps on my prostate. After this I had a biopsy and this was the determining factor that led to my treatment.

      If I had decided not to have that first PSA test, I doubt I would be writing this comment right now.

      Using stats does reveal many older men die with undetected PCa which caused no problems. But what about the younger men?

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    3. Peter Ormonde
      Peter Ormonde is a Friend of The Conversation.

      Farmer

      In reply to Paul Rogers

      I agree with you Paul - up to a point.

      The "treatment" for prostate cancer is a bit like that Vietnam strategy of destroying the village in order to save it isn't it? It can keep the poor bloke alive but what sort of life is on offer?

      It's all very well using the PSA test to identify the serious cases, but without more acceptable treatments and interventions than one is still faced with a horrendous choice - Hobson's Choice in too many cases.

      The PSA test is obviously very effective. But without better options for treatment are we really much better off?

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    4. Margo Saunders

      Public Health Policy Researcher

      In reply to Peter Ormonde

      Are there, in fact, 'better options for treatment'? And are these widely available, or available only for those who can afford them? Just askin'. I recall Alan Joyce (CEO, QANTAS) being full of praise for the type of treatment that he received, but I've never been able to find out how his treatment might have differed from what's generally on offer.

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    5. Rod Govers

      Retired IT administrator

      In reply to Margo Saunders

      I believe, with keyhole surgery, treatment is better today than it was just 12 years ago when I had my radical prostatectomy.

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    6. Chris O'Neill

      Retired Way Before 70

      In reply to Rod Govers

      If, by keyhole surgery, you mean robotic surgery then, apart from the size of the surgical wound, the side-effects (rates of impotence and incontinence) are no better than they are with normal surgery.

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    7. Rod Govers

      Retired IT administrator

      In reply to Chris O'Neill

      Interesting. From people in my various PCa support groups, I've been led to believe side-effects outcomes were better.

      One thing that has been better for me is that the inability to ejaculate or have intercourse has led me to concentrating on the orgasm and they are so much more intense and mind-blowing than ejaculation-focused release. You don't need a full erection to achieve them and with practice they get better and better .....

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    8. Chris O'Neill

      Retired Way Before 70

      In reply to Paul Rogers

      ""Modest?" Spoken like a public health professional and not a personal physician. I would hardly call saving someone's life a modest benefit."

      I'd hate to defend the experts but the writer was using the term in the sense of the ratio of lives saved to the number of tests and treatments performed.

      I note that you no longer give the unalloyed support to Professor Fryndenberg's views that you did when he wrote this: https://theconversation.edu.au/giving-men-choice-the-case-for-routine-prostate-cancer-screening-8633 .

      I presume you would not call saving more than 3000 lives a year a "modest" benefit. How then do you justify not removing the Prostate Glands of all men before they become at risk of developing Prostate Cancer? Is saving 3000 lives a year a modest benefit or not?

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    9. Paul Rogers

      logged in via Twitter

      In reply to Chris O'Neill

      "I'd hate to defend the experts but the writer was using the term in the sense of the ratio of lives saved to the number of tests and treatments performed."

      Of course he was, but that was the point of my criticism. Ultimately this debate should be about patients and not public health statistics. Yes, I understand there is a 'sweet spot', but let's not give patients only the stats advice rather than the personalised health advice.

      Quite a fundamental error I would think.

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    10. Paul Rogers

      logged in via Twitter

      In reply to Chris O'Neill

      Of course I still support the gist of Frydenberg's article.

      For those newer to this debate, and Mr O'Neill's odd absurdity that uses the early removal of prostate glands in a comparative scenario, follow the link to a previous Conversation article and see how I rebutted his obviously untenable position. (Although long and boring for some!)
      http://tinyurl.com/94ed5f9

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    11. Chris O'Neill

      Retired Way Before 70

      In reply to Paul Rogers

      "Ultimately this debate should be about patients and not public health statistics."

      That's a misrepresentation of what's happening. Of course it's about public health statistics. People are given treatment because of public health statistics. You're advised to get treatment because of statistics.

      "but let's not give patients only the stats advice"

      When are they going to get that?

      "Quite a fundamental error I would think."

      Rather an ironic statement. When will I ever get an answer to the question:

      Is saving 3000 lives a year a modest benefit or not?

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    12. Chris O'Neill

      Retired Way Before 70

      In reply to Paul Rogers

      "Of course I still support the gist of Frydenberg's article."

      Perhaps you didn't notice that Professor Fryndenberg is a joint author of this very article https://theconversation.edu.au/psa-screening-and-prostate-cancer-over-diagnosis-8568

      "see how I rebutted his obviously untenable position."

      Sure, if you say so. You simply refuse to believe that people could possibly make a trade-off between quality of life and risk to life.

      Apparently I'll never get an answer to the question:

      Is saving 3000 lives a year a modest benefit or not?

      It must belong in the "too hard" basket.

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    13. Paul Rogers

      logged in via Twitter

      In reply to Chris O'Neill

      You missed the word "only".

      Here is what I would want as a patient (I'm not one, but we're all fair game):

      1. The stats, eg percentages of false positives, negatives, adverse surgery outcomes etc, communicated in a manner that had some meaning for a non-medically trained person.
      2. How this relates to my particular diagnosis, tests and prognosis - PSA, biopsy, family history, other risk factors.

      Is that too difficult to understand? What docs surely need is a clinical practice guideline on PSA testing. OMG, it's on its way:

      http://www.nhmrc.gov.au/your-health/testing-prostate-cancer

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    14. Paul Rogers

      logged in via Twitter

      In reply to Chris O'Neill

      Huh? Of course. Prof Frydenberg is entitled to contribute to an article like this without compromising his earlier contribution. This is an internet "conversation" not a royal commission hearing.

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    15. Chris O'Neill

      Retired Way Before 70

      In reply to Paul Rogers

      "Prof Frydenberg is entitled to contribute to an article like this"

      So where in this article do you support the gist of Frydenberg?

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    16. Chris O'Neill

      Retired Way Before 70

      In reply to Paul Rogers

      "The stats, eg percentages of false positives, negatives, adverse surgery outcomes etc, communicated in a manner that had some meaning for a non-medically trained person."

      Good luck to you then. You could also specifically mention the success rate in making a difference to your outcome. You'll need even more luck to be given that.

      "How this relates to my particular diagnosis, tests and prognosis - PSA, biopsy, family history, other risk factors."

      More or less the statistics applying to your situation. Good luck.

      "What docs surely need is a clinical practice guideline on PSA testing. OMG, it's on its way"

      Oh great. They've been doing PSAs for more than 20 years and finally they're going to come up with a clinical practice guideline on PSA testing. How timely is that!

      You still haven't explained why you prefer treatment with a 2.5% chance of success to treatment with a 4.4% chance of success.

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  2. Dennis Alexander

    logged in via LinkedIn

    My father has had his prostate removed as a result of cancer detection and treatment. His was not asymptomatic. But the side effects have not been fun for him - sometimes he reckons the life he is having might not be even a modest benefit. As a result, I have a PSA every couple of years. Having had a cancerous polyp removed from my bowels, perhaps I'm a little bit careful and given the polyp location, I understand the weighing of life as a modest benefit, sometimes that is exactly what it is, modest.
    What the article does say is the cancer=fatal myth needs to be challenged. Another clear implication is that it is not the test or the diagnosis that is problematic, it is the reflex to radical treatment. As Rod Govers says, the PSA test is a marker that leads to examination that, if problematic, leads to biopsy, and then prognosis, monitoring, treatment etc. We all need to be smarter about how we detect, confront, deal with and treat cancers.

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  3. Colin Kline

    logged in via Facebook

    Hi

    This issue, "overdiagnosis", or "over medicalisation", could apply to all cancers, diseases and genders.

    But the argument : "Information is always better than ignorance" is not at all addressed.

    One can receive information, and choose to act on it, or not.
    Without that information, no such choice is available.

    Also, with information, alternative options can be explored, perhaps less harmful, less painful, less expensive.

    Without information, choice is unavailable.

    This article could therefore have been written by some Govt spin-doctor, or another incarnation of mongrel ministers like Peter REITH, Chris PYNE, attempting to mercilessly prune budgets without compassion or care.

    Bet that spin-doctor would NEVER forego information and treatment for him/herself.

    Cheers,
    'im.

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    1. Julia Thornton

      PhD Candidate

      In reply to Colin Kline

      Agreed. I think the problem is under information, not over diagnosis.

      My husband just had an aggressive prostate cancer removed via radical prostatectomy. It was removed just as it was about to break out of the prostate capsule. Several years of PSA follow up tests yet to go to make sure it had not spread. We're both very glad he had those tests previously. Had it been left, we were told, he would not have survived five years.

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    2. Chris O'Neill

      Retired Way Before 70

      In reply to Colin Kline

      "One can receive information, and choose to act on it, or not."

      Indeed. But that's not what patients were led to believe in the past and the situation may still be the same now. There was no statement that the success rate of surgery at early stages in making a difference to survival was very low. So low, in fact, that it was lower than the success rate of surgery for men who don't yet have Prostate Cancer.

      One thing to bear in mind is that the studies are not comparing early diagnosis and treatment with doing nothing. They are comparing it with treatment after symptoms appear which only occurs in a fraction of cases.

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    3. John Walker

      Project Manager - Security

      In reply to Chris O'Neill

      My story so far: I had a rising rate PSA. My GP sent me to a highly regarded specialist. He did a digital exam and said he felt lumps on one side of my prostate.Then I had a biopsy with 14 samples which detected 3 cancerous specimens (Gleeson 6) My specialist recommended he operate using a robot after I had CT scans etc.
      HOWEVER, my intuition decided to dump my first specialist and I went elsewhere and started again 6 months later. To cut the story shorter, the second specialist said the prostate felt "unremarkable" and the second biopsy with 23 specimens found NO cancer (zero Gleeson) - so I had this pathology re checked a second time and still no evidence of any malignancy.
      So, research your topic, check your doctor, trust your instincts, get a second or third opinion as there are two separate medical camps who don't agree on the best way forward. Cheers John

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    4. Chris O'Neill

      Retired Way Before 70

      In reply to John Walker

      "I had a biopsy with 14 samples which detected 3 cancerous specimens (Gleeson 6)"

      "the second biopsy with 23 specimens found NO cancer (zero Gleeson)"

      That's amazing really but there is the well-known case of Jeff Hoober: http://www.theage.com.au/national/be-wary-of-results-before-rushing-in-20120801-23fn1.html who was told they couldn't find any cancer in his Prostate after it was removed. The Gleason Score is made from a visual inspection of the tissue alteration: http://en.wikipedia.org/wiki/Gleason_Grading_System

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    5. Rod Govers

      Retired IT administrator

      In reply to John Walker

      I would definitely be getting a third opinion in your case, John. It's hard to imagine how you could get two sets of such opposite results.

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    6. Rodney Lovel

      logged in via Facebook

      In reply to Chris O'Neill

      On examination of my removed prostate, the details of tumour was as the preceding biopsy indicated.
      I had the surgery 4 and a bit weeks ago. I have been doing extensive walking most days since my release from hospital, like 4hrs some days and up to 14km, and looking forward to starting running again in less than two weeks. The bladder still leaks a little but is improving each day and nothing that cannot be dealt with easily.

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    7. Chris O'Neill

      Retired Way Before 70

      In reply to Colin Kline

      Colin Kline: "Bet that spin-doctor would NEVER forego information and treatment for him/herself."

      According to "Let Sleeping Dogs Lie?" by Chapman, Barratt and Stockler:

      "So do Australia’s male doctors aged over 50 also “take their own medicine” when it comes to being tested for prostate cancer? One 2002 study from Victoria has given us information on this. It found a minority – 45% – of doctors aged 49 or more had been tested [115]."

      What does that tell you?

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    8. Chris O'Neill

      Retired Way Before 70

      In reply to Chris O'Neill

      There is no Gleason Grade 0. 1 is the lowest. Hence the Lowest Gleason Score is 1+1=2. "Let Sleeping Dogs Lie" states that:

      "In practice, it is unusual for pathologists to report a Gleason score of less than 4 (2+2). Most cancers have Gleason scores between 5 and 10."

      The Gleason score still doesn't make sense to me. Fo example, what is the difference between Gleason 3+3 (commonest and second commonest altered tissue are both 3) and Gleason 3+1? How do they decide the "commonest" and "second commonest" should be separate if they both display the same degree of alteration?

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    9. Chris O'Neill

      Retired Way Before 70

      In reply to Colin Kline

      Colin Kline:

      "Bet that spin-doctor would NEVER forego information and treatment for him/herself."

      Actually, according to Dr Ian Haines: "I am yet to meet a urologist who has had a radical prostatectomy himself although there must be some somewhere." http://blogs.crikey.com.au/croakey/2010/03/22/psa-screening-is-a-public-health-disaster-says-cancer-doc

      So you would probably lose your bet.

      Might be good advice to find a urologist who has actually had a radical prostatectomy if you want someone to perform the operation on you.

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  4. bill parker

    editor wirter

    I would like to know where we have reached in the proteomics studies of malignant prostate cancer.

    To me the idea of finding a specific marker might be more valuable.

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  5. Guy Hibbins

    Medical Officer

    I am bemused by the fact that we so often see articles about cancer screening which do not even mention causation or prevention.

    Why for example does the WHO's IARC Globoscan database show Australia as having the highest age specific incidence rates of prostate and bowel cancer and the second highest rate of breast cancer after Western Europe.
    See http://globocan.iarc.fr/

    With prostate cancer the difference between Australia and East Asia is particularly stark. In 1958 in Japan there were only 16 cases of autopsy proven prostate cancer in the entire country, for example. Now that Japan has adopted a more Western diet and lifestyle they have half the Western rate of the disease and this is increasing rapidly.

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    1. Chris O'Neill

      Retired Way Before 70

      In reply to Guy Hibbins

      "I am bemused by the fact that we so often see articles about cancer screening which do not even mention causation or prevention."

      Indeed. Far more lives could be saved than using our present screening and treatment strategy if we could find out and put into effect the factors that cause the vast majority of the world's population to have a much lower prostate cancer death rate than Australia's: http://www.worldlifeexpectancy.com/cause-of-death/prostate-cancer/by-country/

      It's interesting that…

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  6. John Harland

    bicycle technician

    If the PSA test can detect cancers, why can the antigen not be used to deliver chemotherapies to precisely the right place?

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  7. Chris O'Neill

    Retired Way Before 70

    The success rate of surgery in making a difference to the survival of men diagnosed with Prostate Cancer is so low (2.5%), that they would actually score a higher success rate (at least 4%) if they instead operated on men who don't yet have Prostate Cancer. Ironically they are using the test to choose the wrong men to operate on.

    This bizarre situation comes about because once a man has Prostate Cancer, he has already given up the vast majority of the opportunity (perhaps 90%) to avoid dying from…

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    1. Chris O'Neill

      Retired Way Before 70

      In reply to Chris O'Neill

      Nice to have such a detailed response to my detailed statistics and considerations (nothing but red ticks). Pathetic really.

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  8. Rodney Lovel

    logged in via Facebook

    I have just had my prostate removed due to PC, all contained fortunately.
    The PSA test is only one part of the big picture and some initial information regarding a man's prostate health. Arriving at the decision to remove the prostate involved a lot more information than purely the first screening test, which is just an indicated that we needed to delve a deeper. I think the original article is an gross over simplification.

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  9. bill parker

    editor wirter

    I thought it might help if readers were better informed as to what the PSA actually is. Ralph Valle's succinct (2007) history of the test is here

    http://www.phoenix5.org/Basics/psavalle.html

    One of the things I noted was the value of regular PSA readings - but that said, always use the same pathology laboratory.

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  10. Chris O'Neill

    Retired Way Before 70

    I have a question for all men out there who still have a Prostate gland. Are you or are you not considering having your Prostate gland removed? If not, then why are you taking the risk of dying from Prostate Cancer? If you think you can avoid this risk by early detection then you are dead wrong.

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  11. Sue Ieraci

    Public hospital clinician

    I have just done a quick scan of local Urologists and each website had a wealth of patient information. It is also easily accessible on the Cancer Council website. I know not all elderly men have internet access but there appears to be a wealth of easily accessible information about diagnosis and therapeutic options. Perhaps patients are being better informed than some people assume.

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    1. Chris O'Neill

      Retired Way Before 70

      In reply to Sue Ieraci

      I don't know that I'd call it a "wealth" of information but there's a lot of information about all the detail involved. Statements like:

      "Your doctor will consider your test results, the rate and depth of tumour growth, how well you respond to treatment, and other factors such as your age, fitness and medical history. These factors will also help your doctor give you advice on the best treatment options and let you know what to expect"

      are statements of a general nature and don't provide any hard information.

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    2. Chris O'Neill

      Retired Way Before 70

      In reply to Sue Ieraci

      "Perhaps patients are being better informed than some people assume."

      I still haven't found any clear statement on those websites about what the likely success rate of treatment is and how this compares with the risks that virtually everyone takes to avoid the high risk of damaging their bodies' functionality.

      Perhaps patients aren't being as well informed as some people assume.

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    3. Chris O'Neill

      Retired Way Before 70

      In reply to Chris O'Neill

      Perhaps the red-tickers would be considerate enough to point out what these websites are that provide information about the likely success rate of treatment. More likely they are just childish and pathetic.

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