Sunday, May 22, 2011

Is This The End Of Prostatectomies?

The annual meeting of the American Urological Association was rocked this year by the release of  PIVOT (Prostate Cancer Intervention Versus Observation Trial).  Journalists at the event stated that the presentation of the data brought a “collective gloom” over the hall filled with urologic surgeons.  The reaction is not surprising as the study basically concluded that radical prostatectomy is not necessary for the management of anything other than aggressive prostate cancer.  So does this study mark the beginning of the end for the widespread use of radical prostatectomy for the management of prostate cancer?  I think that in order to answer this question we first need to take a closer look at the design and results of the study.


PIVOT Study

The PIVOT study was created in 1994 to determine whether the use of prostatectomy in treating prostate cancer added to overall survival and cancer specific survival.  The study was designed to recruit 5000 men (less than 75 years of age) with newly diagnosed, localized prostate cancer.  Men eligible to proceed were then randomized into one of two groups:
1)      Prostatectomy: Actually, only 78% of men in this group underwent prostatectomy   while the rest underwent other therapies
2)      Observation:  Patients in this group did not undergo any treatment aside from palliative therapy for symptomatic management of metastatic disease

The patients in the two groups were then followed for an average of 10 years .

Results of the PIVOT Study

Before I get into the results of the study, I want to stress that just the basic data has been provided and, until the actual paper is published, the nitty gritty of the data cannot be really assessed.  Nonetheless, even the basic data that is available definitely provides a starting point for discussion.

Out of the 5000 patients recruited for the study, only about 700 of the eligible patients actually agreed to proceed.  These 700 men were then divided into two groups with, on average, similar characteristics in terms of age and degree of prostate cancer.  After an average of about 10 years of follow up, the results reported by the study were definitely eye opening:

1)      While 48% of the men in this study died within the 10 years of follow up, only 7% died from prostate cancer
2)      Prostatectomy led to an insignificant, absolute 2.9% increase in overall survival. 
3)      Prostatectomy led to an insignificant, absolute 2.7% increase in prostate cancer specific survival.
4)      For high risk patients with PSA greater than 10, prostatectomy provided a significant, 7.2% increase in survival.

Initial Reaction to the Results

Upon first glance at these results, it is not unreasonable to come to the conclusion that radical prostatectomy is an unnecessary procedure for the majority of men diagnosed with prostate cancer.  After all, with PSA screening, most men are diagnosed with low or moderate risk disease and a PSA well below 10.  This trend towards early stage disease is also demonstrated by the study itself in that 70% of men participating in the study had a Gleason score of 6 or less and 72% were classified as either low or intermediate risk.  If we take the study population as a microcosm of the general population, we would argue that over 70% of men simply do not need to undergo prostatectomy (or any other treatment for that matter) to treat prostate cancer.  We would argue that men should not expose themselves to the significant risks and quality of life impacts of prostatectomy for only a minimally higher chance of surviving prostate cancer.  We would then conclude that treatment for prostate cancer should be reserved only for those men with high risk cancer and a PSA greater than 10.  With the general data provided, these conclusions may very well all be true.  Before hanging up the scalpel for good, however, I thought I would take a closer look at the data.

Digging a Little Deeper

After my initial shock from these results wore off, two big questions became prominent in my mind:

1)  How healthy were the men in the study?  As I noted above, approximately half of the men in the study died within the 10 years of follow up.  Only a small percentage of these men died of prostate cancer.  There are two possibilities to explain the small number of men dying from prostate cancer:

A)   The low risk prostate cancer that afflicted most of the men in the study was just not that lethal.
B)   The men in the study had other health problems that were more lethal than prostate cancer.

The answer is probably a mix of both.  Men with significant medical problems (heart disease, stroke, diabetes) often do not live long enough to be affected by or to die from prostate cancer.  At this point you are probably thinking that I am proving the point of the study: most low or intermediate prostate cancer does not need to be treated.  However, not all men have significant medical problems.  Healthy men, particularly healthy young men, may well live long enough to suffer from and even die from prostate cancer.  A famous, large European study recently demonstrated that, when looking at men as a whole, 50 men with prostate cancer would need to undergo prostatectomy to save one life from prostate cancer.  HOWEVER, a follow up study then went on to demonstrate that, when looking at HEALTHY men, only 4 men with prostate cancer would have to undergo prostatectomy to save one life from prostate cancer.  Quite a difference! Unfortunately, I believe that the PIVOT study is too small to demonstrate this type of distinction.  Nonetheless, I hope that when the final, more specific, data from the trial is published, information about the overall health of these men is included to help us determine whether their overall health precluded them from benefiting from prostate cancer treatment.

2) Why was the study only carried out for 10 years?  During my residency training I, like most other urologists-to-be, learned that men with a life expectancy less than 15 years probably should not undergo aggressive treatment for low risk prostate cancer.  Studies have demonstrated that prostate cancer typically takes around 15 years to create metastatic disease significant enough to be lethal.  As a result, men that did not expect to live that long would not derive any benefit from treatment.  This previous data makes it not very surprising that, at 10 years, only a minimal survival advantage was noted in PIVOT for men undergoing treatment versus those men that chose to observe their cancers.  At 10 years, metastatic prostate cancer starts to present itself but usually not to the extent that can kill.  I would imagine that, like in previous studies, metastatic disease was found more often in men in the observation arm of the PIVOT trial.  I am not sure, however, that this was an endpoint recorded for the trial.  I would bet that if the investigators running the PIVOT trial would continue to collect data up to the 15 and 20 year marks, the tiny difference demonstrated in the survival curves  of men in the treatment versus observation arms of the study would prove to be only the initial separation point of two very divergent curves.

Of course, the average age of the men in the study was 67.  Men in this age group have a life expectancy of about 15 years so, for them, a survival benefit achieved 15-20 years after surgery is pretty useless.  But what about a 50 year old man?  His life expectancy is over 30 years.  For him, a survival advantage 15 years after surgery can mean the possibility of 15 extra years of life.  I don’t think the value of this survival advantage is really debatable.  This concept was demonstrated in a recent study of Scandinavian men with prostate cancer which, after 15 years of follow up, demonstrated a 38% survival advantage for men younger than 65 years of age undergoing surgery as opposed to observation.  For this reason, I feel that while the 10 year survival data from this study may be helpful in guiding a treatment (or no treatment) decision for a man in his late 60s or 70s, the data is not relevant to a healthy man in his fifties. 

Take Home Message

The purpose of this post was not to criticize the PIVOT trial.  Any well run, randomized trial evaluating 700 men deserves significant attention and must be taken very seriously.  The study, indeed, reaffirms many important concepts in the management of prostate cancer.  First, men with low risk prostate cancer should definitely be advised of the option of active surveillance, particularly if they are in their 60s or older and/or if they have significant medical problems.  These men, as the study demonstrates, may not derive significant benefit from prostatectomy or other treatments.  In the same vein, men with aggressive prostate cancer should be offered treatment, even if they are older or may have some other medical problems.  These aggressive cancers, as demonstrated by PIVOT, can lead to premature death even within a 10 year time frame. 

What the PIVOT trial does NOT prove to me, however, is that prostatectomy is useless for YOUNG, HEALTHY men with low or intermediate risk prostate cancer. Of course, these young men need to be counseled on the risks and quality of life implications of treatments such as prostatectomy. They need to be told that any survival advantage from surgery or other treatments would not be enjoyed for more than a decade. They also need to be advised of the risks and benefits of active surveillance as well.  However, until large, randomized, long term studies prove otherwise, I believe that these young, healthy men should not be told that treating their prostate cancer is unnecessary.


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This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician

8 comments:

  1. "Of course, these young men need to be counseled on the risks and quality of life implications of treatments such as prostatectomy."

    You mean having the cojones to tell them that they'll end up in diapers and have 30 years of life left to spend in platonic relationships, bereft of intimacy and physical contact?

    Rushing, bullying, and deceiving young men with very low and low risk prostate "cancer" (a little wager: within a decade what is now called 'very low risk' or 'indolent' PCa will be reclassified as something else before 2020) into treatment that could be postponed for decades, if not forever, with inevitable devastating, quality-of-life destroying, irreversible effects is inexplicably cruel (note I did not use the most disingenuous of self-justifying phrases, 'side' effects). The degree to which the urology and oncology community dissembles to patients and mitigates itself from the consequences of these treatments is shameful.

    "However, until large, randomized, long term studies prove otherwise, I believe that these young, healthy men should not be told that treating their prostate cancer is unnecessary."

    Who said anything about not treating YOUNG, HEALTHY men with very low and low risk PCa? Of course they need treatment - but most of them don't need to START their treatment process by having their penises shortened by 1.5-2", never ejaculating again, giving up the experience of orgasm, and not being able to have an erection for months, years, or FOREVER!!!

    I know all you guys are still trying to pay off your Da Vinci's and want to make sure you have a market available, but haven't you seen the research that shows it's possible to make MORE money from managing men under Active Surveillance protocols than a one-hit, right-off-the-bat surgery?

    Better yet, why don't you be the first-kid-on-your-block to adopt lesion-specific focal therapy techniques? You can get that cool new Artemis technology that lets you overlay MRI results onto a guided ultrasound so that you can pinpoint where the actual lesions are to biopsy, zap w/ some cryo or those cool little laser spurts of PCa-destroying energy...

    And then you get to keep following them, running tests, checking to make sure there aren't any residual cancer cells to zap away again, and some will even need you to break out the old Da Vinci...

    Prostatectomy is a bitterly cruel pill-to-swallow of a treatment - PARTICULARLY for young healthy men. Someday (hopefully very, very soon) it will be remembered with shudders as the male sexual health equivalent of radical, take-everything-even-vaguely-related-to-sexual-reproduction hysterectomies of the 1950-80s for non-life threatening conditions like... menopause and 'nervousness' or early breast cancer treatments that simply involved lopping women's chests in concave hollows.

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  2. Everyone's life will be so improved when the urology community decides to treat very-low and low risk prostate cancer like a chronic disease to be managed, rather than as immediately life-threatening when the evidence so overwhelmingly proves that it isn't and when the urology community will take responsibility for ALL the outcomes of the treatments it provides including the ones that diminish men into home-bound, diaper-clad eunuchs.

    I'm sure there were plenty of docs who managed polio with iron lungs and leg braces who were beside themselves at the thought of a polio vaccination, yet who would argue that we're not all better off that those particular medical treatments have been rendered obsolete.

    Physicians have to own everything they do - not just claim the outcomes that justify their business models and make them feel good about themselves. If a urologist insists upon ‘overtreating’ a man with a radical prostatectomy when he didn't need it, based on an arbitrary criterion like age, that urologist has done more harm than good - horrible and irreversible harm.

    Tracy Greever-Rice (You ought to let people know who you are. Potential patients have a right to understand your attitudes toward their whole health, not just whether or not their prostate has a minute foci of indolent PCa)

    P.S. Your interpretation of the Scandinavian trial is spurious (as were many others' interpretations, I'll grant you that). The men in the Scandinavian trial - both young and old - were NOT diagnosed with 'low risk' PCa. They were not even necessarily diagnosed with organ-confined PCa! Those in the non-treatment arm were not on AS protocols but on watchful waiting protocols - palliative care without intent to cure. So, while maybe you've got it worked out in your head that it's okay to unnecessarily, permanently maim 3 or 6 men to prevent one man from eventual prostate cancer mortality (as if the quality of those mens' lives have no value), you don't get to make that claim based on these two studies. These two studies don't tell us ANYTHING that should preclude treating young men conservatively and with high priority given to maintain their quality of life.

    It is DEEPLY disingenuous and puts the quality of life of thousands and thousands of men at risk for you (or anybody else who's currently making a buck off the current 'standard of care') to interpret either the Scandinavian trial or the PIVOT trial as relevant in ANY way to men <60 with very low risk and low risk PCa.

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  3. Tracy: I can see that you have very strong opinions about prostatectomy. A few thoughts on your comments:

    1) If you read the other posts on my blog you would see that I am very open about lifestyle impacts and complications of prostatectomy. While I cannot speak for all Urologists, I would hope that the majority of them take the time to discuss these issues thoroughly with their patients before undertaking surgery.
    2) If you read the other posts of my blog you would see that I am actually a strong advocate of active surveillance for patients with low risk prostate cancer.
    3)You seem to misunderstand the point of my post which is not an endorsement for prostatectomy but, rather, a warning to young healthy men to not apply the findings of the PIVOT trial ( a study composed of men in their late 60s and early 70s) to their own situations. My point, as I mentioned in the post, is that men in their 50s should not do "nothing" but, rather, seek treatment in whatever capacity. While you appear knowledgeable about some aspects of prostate cancer, I assume you are not a physician and have not dealt with young patients who, when hearing that not doing anything for their cancer is an option, take that as validation of ignoring the fact that they have cancer once and for all.
    4) My point about the Scandinavian trial was about the time frame as the earlier results( less follow up) from the same trial did not show a difference in survival across the board, like the PIVOT trial. The later follow up did.
    5) My reason for anonymity speaks exactly to the point you make. I DO NOT want this blog to be a source of business for my practice. I DO NOT write this blog according to the business model of a practice. I write it to provide some unbiased information to readers who chose to read it. Like you, they are free to disagree with it. The one thing I ask from my readers is to be courteous and respectful to each other and to me. I would request that you adhere to that request if you wish to post future comments. I sense some obvious anger in you about prostate surgery that I would assume was generated from a VERY bad experience. I think that experience deserves to be shared with others. However, I feel that it is deeply disingenuous of you to generalize your experiences to those of all men with prostate cancer. While it may seem shocking, many men actually live happy, cancer free lives after going through treatment for prostate cancer, whichever they may choose.

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  4. The anonymity is a good thing -- shows a doc giving something back by providing information and thoughtful analysis without expecting anything in return. Keep it up!

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  5. Your postings are a really valuable source of information to weave into the complex picture of my prognosis and my personal plan for handling my prostrate cancer.
    Keep up the great work,

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  6. Balnastraid: Thanks for the positive feedback! I am happy that is helpful.

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  7. Tracy, I was 43 when I had my prostate removed with bilateral nerve preservation in March 2011! My post surgical Gleason was 6, 2 positive margins, microscopic bladder neck involvement with clear margins, nodes clear, seminal vesicles clear.

    To date my PSA is undetectable. As for incontinence, three months after surgery I stopped using pads entirely. Afterwards, I had a stress leak almost daily. Today, it's down to maybe 1-2 leaks a week! Actuall, at 9 months I did some pretty strenuous yard work with NO leaks.

    Now on to what concerns ALL guys in the PCa boat...impotency or ED. First off, before my surgery I was 100% potent! Never relied on anything, but my loving wife! She was all I needed! I was given the green light to have sex 6 weeks after surgery. Well, as expected I was as limp as you can be! I even leaked urine on my wife! But, I had a wonderful orgasm! Yet, I was embarrassed and yes I cried, but my assured me it was OK. She kept saying that I was expecting waaaay too much. My surgeon and his PA agreed with her! Although, I was given a Rx for Viagra it didn't seem to help for months and during those months I never penetrated my wife...talk about depression! Then at about 6-7 months whamo! I could tell during the day, while at work nonetheless, that something was coming alive down there! One night in particular after a Halloween party before we got home I took 1 100mg generic Viagra (online pharmacy). When we got home and started our foreplay there it was not as rock hard as pre surgery but, definitely useable! That night was the first time after surgery I had actually "made love" to my loving wife. It was so good I was able to go again in about 15 mins!

    Almost a year out I am able on some occasions have sex without the pill. Those time when I do I use 1/2 a pill. The orgasms don't have the same satisfaction at times as actually "cumming", but they are definitely GOOD. Sometimes, it's hard to say why, but they are mind blowing!!! As a whole though, ejaculation is better.

    My surgeon says that my continence and return to potency is far ahead of all his patients. Of course, he attributes this to my age...I'm his youngest patient. He has performed over 1000 RP's. So surely, his skill played a role too.

    So see Tracy all is not gloom and doom with surgery! But, of course, I would be nieve to think that my age didn't playe a large role in my recovery. To be honest, I doubt I would have had surgery if I was in my 60+ years of age.

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  8. I just want to share this personal story about how my husband survived the problem of NO ERECTION after prostate surgery.
    My husband undertook prostate surgery 3 years ago and before then i always looked forward to great sex with him and after the surgery he was unable to achieve any erections, we were bothered and we tried so many drugs, injections and pumps and rings but none could give him an erection to even penetrate. I searched for a cure and got to know about Dr. Hillary who is renowned for curing problems of this nature and he did encouraged me not to give up and he recommended his herbal medication which my hubby took for 3 weeks and today his sexual performance is optimum. You too can contact him for similar problems on hillaconn@gmail.com. A man who cannot satisfy his wife's sexual need is not a real man!

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