Is NO treatment best???

In this week’s NEJM, an article appears from a VA trial that was started in in 1994 and accrued patients through 2002. Of 13,002 patients who were diagnosed during this period, 5032 were eligible to participate but only 731 (~15%) men chose to do so. This highlights the first important issue: MEN do NOT participate in clinical trials the way women do. It’s a shame considering how many questions we have to answer. To be eligible, you had to be less than 75, fit for surgery, have PSA < 50, a small tumor, and a negative bone scan. (this applies to the majority of patients we see these days). The participants were then randomized to observation vs. surgery. WHOA, you mean some men were willing to NOT have treatment……yup…and hats off to the guys who participated !! Half of these guys were detected only because of PSA screening.

Of the 364 assigned to surgery, 281 had a radical and 53 didn’t – 14 had radiation. Among 367 assigned to observation, 36 changed their mind and had surgery and 29 received radiation therapy. By the end of the study, about half of the men had died.  (the median survival was 13 years  – sobering for those of us in our late 60’s) Only 52 of the deaths in the study were due to prostate cancer. Overall, the only group who benefited from treatment were those with  PSA >10 in terms of prostate cancer deaths. “In contrast, among men with low-risk cancers (as determined by a PSA value < ng per milliliter, a score of 6 or less on the Gleason scale, and a stage T1a-c or T2a tumor), there was a 15% non significant increase [my emphasis] in mortality among men assigned to radical prostatectomy…” Intermediate-risk patients (PSA 10-20 or Gleason 7, or tumor on both sides of the prostate) had a 31% decrease risk of dying from all causes, but only 6 of the 59 deaths in this group were from prostate cancer.

For all those who feel that prostate cancer screening “saves lives”, this is a really important trial to know about. If NO treatment is better than treatment in many men, then one wonders why we should screen for this disease. The “cost” of treatment was pretty high. 81% of the surgery patients had erectile dysfunction and 17% had urinary incontinence. I am sure there will be a flurry of commentary in the news media this week. One question is whether the men who have been treated over the past decade will reconsider whether they made the right decision. I doubt it. Once treated, the most satisfying thought is that the side effects were “worth it to be cured” – a cure that might not have been needed – yet 90% of men with low risk disease receive either surgery or radiation.

 

 

17 Comments

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17 responses to “Is NO treatment best???

  1. Dick Beck

    I had a PSA of 7.6 and then 11.9 5 months later. Biopsy shows Gleason 9 throughout entire prostate. And your recommendation is NO treatment? And you want to abolish PSA testing? I disagree. If you think it is over-tested, over-diagnosed, and over-treated because the test is unreliable and the treatments have negative quality of life issues then get busy and develop a reliable test and a cure, not expensive inneffective treatments. If 250,000 men in the U.S. are diagnosed each year, and over 25,000 die each year, the disease needs more attention, not less. Discouraging men from PSA testing will lead to later diagnosis and more deaths.

    • Dick,
      What we have is indeed challenging. The problem is that for every case like yours, there are many more like the low grade cancers that get treated. I sincerely appreciate your comments, but having devoted most of my 34 year career to prostate cancer research, I feel like I have been pretty busy trying hard to do just what you say and there has definitely been some progress. Never-the-less, in 2012, as things stand, I feel there is a compelling argument from this study and others to say that screening is not where we need it to be and until it is, there may be as much harm as benefit. At the very least, men need to know these kinds of studies exist and the implications of being found to have a low grade cancer BEFORE they agree to screening. That is called informed consent, and at present, I think we usually fall short of achieving the desired level of understanding the nuances and implications of screening before guys hold out their arms for a blood test and lean over for the DRE. I have had the opportunity in some screening clinics to explain the details in a brief 5-10 minute chalk talk, and it is VERY clear that the mass screening that goes on in health fairs attracts men who feel that “screening saves lives”. This study points out that it may also cost lives in some men and that the majority of men who die after their 60’s die from other causes, even if they have been diagnosed with prostate cancer, treated or not. There are many aspects of the study (e.g. do VA patients represent the “real world”, would it have been different if more men would have been willing to participate, etc.) that can be criticized, just as criticism has been directed toward various flaws in the two large screening studies. The reality is that this is a disease of aging, most men have prostate cancer at the time they die if they are in their 80’s, and those who never knew about it might be better off having not dealt with the psychological burden of a “disease” that never hurt them.

      • Dick Beck

        Michael, thank you for your reply. I certainly appreciate that there are many conflicting views regarding screening and treatment of prostate cancer. I have had a radical prostatectomy which revealed lymph node involvement. I am stage IV and currently undergoing continuous androgen deprivation therapy. So in my case we do not yet know whether I will be the 1 in 1000 whose life was spared as a result of screening. Clearly the psychology of coping with a cancer diagnosis makes it quite difficult to understand or accept a theraputic recommendation of “let’s just wait and see”. Perhaps if men had the same motivation to action that women have displayed in pursuing a cure for breast cancer we might be having a different conversation. So let’s continue to advocate for more research for prostate cancer to provide better screening and curative treatments.
        PS: Do you know where I can view the complete NEJM article that you referenced and the related NEJM editorial?

      • David Chaklai

        Not screening because MDs & their patients may use the information erroneously and choose unneeded procedures is a ludicrous notion. So a patient with a high grade cancer, that may still be contained, is sacrificed so that another won’t ‘know’ to treat a indolent tumor that should’ve been left alone? The PSA test is far from perfect, but unlike many other cancers, with this test, cancers can be detected well before symptoms of progression are present. What you seem to be proposing is akin to an ostrich approach. Since we can’t trust our oncology/urology community to make accurate recommendations regarding prostate cancer, lets not test for it all. Is the current quality of urologic care so poor that we are better off being kept in the dark?
        For a gender that is notoriously uncomfortable seeking medical care, especially when it may involve sexual funcion, discouraging men to screen for a disease that is curable when contained, makes no sense at all.

      • David (and others who feel screening should be continued in spite of potential harm:
        First, thanks for the many heartfelt responses. I fully realize this topic is not an easy one.
        I invite you to read editorail on the topic in last weeks Lancet.

        In case you can’t make the link work, here are the final two paragraphs:
        “Facts, as John Adams observed, are stubborn things. But are facts more stubborn than doctors’ opinions—and what is the way forward? Although it is possible to say, dispassionately, that prostate cancer is a disease more die with than die of, and to repeat the old saw “first do no harm”, the PSA genie is now out of the bottle. While some doctors and patients might be unconcerned by the presence of a slow-growing, non-symptomatic, and very possibly non-fatal cancer, others, quite understandably, feel differently. After all, for some, it is an aggressive, terminal disease. High expectations of physical health in an increasingly consumer-driven system add to the pressure on doctors to help patients make the right decisions. Doctors are not simply the keepers of a store of information, investigations, and treatments: they are advisers and navigators. The PIVOT study indicates the need for better prostate cancer screening methods and understanding of the disease, and provides evidence for watchful waiting as an appropriate form of management for some—perhaps many—patients. It is also an opportunity for doctors and patients to ask themselves what they want from medicine.”

        “For most of its history, medicine has been limited by what is possible: its reach has exceeded its grasp. Rapid technological advances in the past 100 years have, in many areas, reversed this situation. In the early 21st century doctors often find themselves asking not what investigations and interventions can be done, but what should be done. As in the case of PSA screening, there is a real risk that intervention may be worse than observation. The current buzz around medicine’s “creative destruction” via genomic sequencing and smartphones constantly monitoring physical parameters raises the possibility that medicine might yet snatch defeat from the jaws of victory. Would constant checking for disease be reassuring, or would it interfere with the actual business of living? The empowerment of patients with information, where possible from appropriate physical tests, is to be encouraged: but striving after a technology-driven, purely biomedical model of perfect physical health is no form of empowerment at all. The PIVOT trial is a timely reminder of medicine’s—and life’s—imperfections. To the Hippocratic Oath might be added: I will not request an investigation unless I am confident that the answer, and the actions I take on its basis, will substantially improve my patient’s life.”

        I suppose my blog didn’t do the discussion justice, but maybe the more sophisticated commentary from the Lancet editors explains it better. I would only add that David’s hypothesis of saving one patient the pain of knowing he has cancer in order to find another patient with an early aggressive cancer does not accurately reflect the equipoise in my opinion. What if the number is 48:1 as suggested by the European trial in terms of number needed to treat to save one life? 44 of the treated patients will have significant sexual side effects. If we assume half will be watched, then 24 will have repetitive biopsies with 1-4% risk of sepsis with each biopsy. And on it goes. Again, I am not AGAINST screening. I am not FOR screening either. I am FOR having men fully understand the can of worms issue involved in screening, before they have their blood drawn or DRE performed. THEY should make their own choice, and what I fear is that far too few can really appreciate the kind of discussion that has gone on in this blog given the time/thought that we have all put into writing down our thoughts from a pretty infomed perspective (and how little time men spend in reading informed consent documents).

  2. Absolutely agree that research is the key and that women have been way ahead of us in teaming up with scientists/physicians and getting the studies done that answer questions. Moreover, I would argue that unlike prostate cancer, the treatment teams (surgery, radiation, medical oncology) have learned how to effectively collaborate rather than compete. I have been in a number of conferences where the urologists worry excessively about “losing our patients”. I am fortunate to practice in an academic setting where this is not the case and we all evaluate each other’s cases from the outset to try and come up with a comprehensive plan. An example of where things are going in this regard is here: http://chicago2012.asco.org/ASCODailyNews/Abstract4521.aspx
    As for the NEJM article, you have to have a subscription to read the whole thing, or be at a hospital or med center that has a subscription. You can read the abstract at: http://www.nejm.org

  3. Joe Blue

    The screening debate assumes that men will continue to make bad treatment decisions. “If NO treatment is better than treatment in many men, then one wonders why we should screen for this disease.” Why not separate the screening decision from the treatment decision? Give men being tested better information about treatment outcomes based on the result of their test. Put the emphasis on helping men make good treatment decisions. Perhaps those with low PSA’s are better with wait and see, while those with very high PSA’s may be too late for treatment to work. But why deny the guys in the middle a chance for a longer and better life by telling them not to get tested?
    Many thanks for your terrific blogs.

  4. I don’t advocate denying men anything. What they are being denied (in my opinion) is ENOUGH knowledge about the consequences of having a psa drawn, then finding out they have cancer, and if it is a low grade cancer, living under the “cloud” of knowing about it. The psychologic burden is clearly not trivial, and many men understandably will elect treatment for a “disease” that would never hurt them, then pay the price of the side effects. If they truly understand that risk, then the idea of separating diagnosis from treatment is a reasonable position. I haven’t seen many men who can live with ignoring the diagnosis. At a minimum they enter “active surveillance” with all of the anxiety that creates on a quarterly basis, never mind the discomfort and risk of repetitive biopsies. No one who has been through this seems ready to accept the concept of the happy majority of men in their 80’s who don’t know about their cancer and die of other causes, never having to deal with the difficult choices. I am fully aware of the occasional man whose life is saved by screening. What I’m arguing for is high quality information/knowledge before that choice. Maybe I’m not being clear enough about this concept…however, many physician friends of mine over 65 are choosing not to be screened and I think that is fine.

    • Dick Beck

      Michael, I still have an issue with the direction of this conversation. I think that it should be made very clear that the PSA test does not provide a diagnosis of cancer. It merely provides an indication of whether additional investigation or testing could be considered to determine if there is cancer. It is the follow up testing, usually a biopsy that actually determines if it is cancer or not. I believe that the follow up testing is necessary to assess the agressiveness of the cancer which is usually determined by the Gleason score. It is at this point that the discussion with the patient needs to get into extensive detail regarding the implications and the consequences of treatment options. I still do not hear anything being discussed about an alternative to the current method of PSA and biopsy for diagnosis. The fact remains that PSA screening and follow up biopsy are all that is available at this time. Until such time that better testing methods are available for early detection and diagnosis we should neither abandon nor discourage the use of what is currently available. We should continue to encourage early detection which improves the liklihood of cure, not suffering with palliative treatment, which usually is the outcome when detected at late, advanced stages. We should not be suggesting that anyone stick their head in the sand and cross their fingers in blind hope that they will live to be “happy . . . in their 80’s”.

      • I guess we will just have to disagree in a mild way. Your approach is willing to accept harm in a large number of men to find out who might be helped. By harm, I mean that all positive men now live with the burden of a cancer diagnosis (which by the way makes them ineligible for life insurance) and needing to make a choice that is by no means easy nor clear. As the study indicates, the men who are surgically treated with low grade cancers may actually have an increase in mortality. Many of these individuals understandably are completely frightened into treatment by the word “cancer” and are emotionally unable to not be treated. Combining that with the lack of evidence at the macro level that “prostate cancer screening saves lives” in the two very large studies, I tend to give a lot of credence to the old medical aphorism, “first do no harm”. I am fully prepared to agree that there can be harm in either screening/treating, or not screening/treating up to around age 75. After that, I don’t think it is very hard to come down on the side of not screening unless someone is insistent, and then, it is “freedom of choice”. For that matter it remains freedom of choice all along at this point, so it really doesn’t matter much what either of us think and that is as it should be. Informed men can make up their own minds. Too many, I fear, are ill-informed.

  5. Joe Blue

    Perhaps we agree that the correct path is
    1. High quality information/knowledge before the screening choice
    2. IF the man chooses screening and tests positive, more information based on level, biopsy etc.
    At each point the information includes all the trade-offs.

    In other words we do not presume to make the decision for men. We give them the best information we have so they can make their own choices. What do you think?

    • Completely agree. The challenge is to make #1 high quality before referral to urologists. They understandably feel that if someone is referred they are obligated to biopsy or else face liability issues if there is a bad outcome down the road. And getting the kind of time to transmit knowledge of the pros and cons done in a primary care setting is tough.

  6. Joe Blue

    Could the American Cancer Society or similar organization write, post and maintain easy-to-read information on the web? PCP’s could refer their patients to it.

  7. Dan

    Dr Glode, I can understand the point of view you present , and surely much harm has been done to many men as a result of being diagnosed with an insignificant cancer. For Me I am over 6 years out with high grade metastatic PC ,actually gs5+5 as confirmed by Jon Epstien, psa in the hundreds with widespread bone mets, I have maintained a good QOL as I passed through zolodex,nilandron, casodex,HDK,TDE, and now failing zytiga(worked for 1 month) TDE gave the most time 3 years,do you think DES would work after that?.My question now, Is it worth it to do chemo and ruin that qol that I have had,has taxotere given much benefit, or is it the chemo that makes them sick. If so do you reccomend q21taxotere, or every 3 out of 4 weeks.

    • Dan, I don’t give specific advice here. That said, first – very sorry for your situation, but glad you are focusing on qol. My experience is that taxotere is reasonably well tolerated by most men and probably “worth it” when/if symptoms arise. I have taken care of some men who were in deep trouble with symptoms that nearly disappeared with a few cycles. I have also had experience with individuals who had nothing but a rising psa and then had drastic complications due to side effects. So, generally I advise waiting until symptoms appear before jumping to toxic treatment. I have also had folks who didn’t tolerate q21 days and did much better on 3/4 or 4/6 lower dose regimens. Hope that helps.

  8. Dan

    Dr Glode,
    Thank You for your response.
    Fortunately my cerrent labs show a 30% decline in psa after 4 months on zytiga. So for now I am a responder and I will go from there.
    Dan

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