Seven critical prostate cancer controversies

Long-time prostate cancer advocates (and of course all members of the clinical treatment community) are well aware of the controversies that complicate testing for, diagnosing, and managing prostate cancer. However, for men approaching their mid 40s and early 50s and newly diagnosed patients this can come as a major shock.

What we thought it would be useful to do would be to provide people with a list of seven really well-known and truly controversial issues that affect and complicate risk assessment for, diagnosis of, and treatment of prostate cancer. These are issues that affect very large numbers of men, and are truly divisive — not just for patients but also for many in the prostate cancer treatment community, which is why they are so problematic, and why, if you are a patient, who you choose as your doctor(s) can profoundly affect how your condition is assessed, managed, and treated.

Now let us be very clear. The seven controversial issues listed below are by no means the only controversial issues in the world of prostate cancer. However,

  • The first two affect every single male in the world.
  • The next three affect every single male in the world who is diagnosed with prostate cancer.
  • The last two are highly likely to affect every single male in the world who has progressive prostate cancer.

From that perspective, they were the seven most important controversies that we could identify.

So, here we go:

  • Who should receive regular tests (“screening”) for risk of prostate cancer and how? This is a hugely controversial question that affects everything about the diagnosis and management of prostate cancer. The truth is that we really don’t know the right answer to this question. We’ve been working on it for 40 years. We do know that many men who are diagnosed today with low-risk prostate cancer are being diagnosed with a biological condition that will never have clinical consequences if it is left untreated. We also know that if we stopped all PSA testing of asymptomatic men tomorrow, then the risk for diagnosis of clinically significant and metastatic disease would (slowly) return to the levels evident in the mid to late 1980s.
  • Does ANYthing actually prevent prostate cancer? People swear by all sorts of different things from vegan diets to patented nostrums. In fact, there is a host of things that we can do that may lower risk for a diagnosis of prostate cancer, but nothing (we repeat, NOthing) has ever been proven to lower risk for the onset of prostate cancer by even 50 percent among undiagnosed men in a well-structured, randomized clinical trial. If you exercise regularly and eat well (i.e., eat healthier types of food and keep your body mass index within reasonable limits) this on its own will lower your risk for a multitude of chronic diseases … but it won’t eliminate risk for any of them (prostate cancer included).
  • Who does NOT need immediate treatment for low-risk prostate cancer and how can we best identify them? We do know that many men with low-risk prostate cancer don’t need immediate treatment. This group of men definitively includes the patients who have indolent disease and who will never have any significant clinical symptoms associated with their prostate cancer in their remaining lifetime. The problem is that we don’t know how to identify these men with accuracy. We also do know that many men with low-risk disease can certainly delay having treatment for some or for many years and still be given effective (curative) treatment when it becomes apparent that they really need it.
  • Can we actually cure prostate cancer in MOST men diagnosed with high-risk disease? We know that we can cure (i.e., eliminate prostate cancer in) some men with high-risk, apparently localized disease. We also know that many men initially diagnosed with high-risk, apparently localized disease are not cured and will progress (over time, which may be many years) to have metastatic prostate cancer which can lead to their deaths. However, we really don’t know why we can cure some of these men but not all of them … however early their disease is identified. Why? Because we don’t have simple ways to tell whether their disease really is localized at the time of diagnosis, so treatment is a “hit or miss” affair based largely on guesswork.
  • What is the “best” type of treatment for localized prostate cancer? We don’t know. There are many options, and some physicians definitely have very strong opinions about this. Almost none of the different options have been compared to each other in well-designed clinical trials in well-identified groups of patients. All that any truly honest clinician can tell a patient is that he (the patient) appears to be a good or a less good candidate for a particular type of treatment. Most newly diagnosed patients with localized prostate cancer are at least decent candidates for several different types of management.
  • When should androgen deprivation therapy (ADT, also known as “hormone” therapy) be started in men with progressive prostate cancer? Again, we really don’t know. Some physicians like to start ADT early; others like to avoid using ADT for as long as they can. There is no right answer to this question.
  • Is intermittent ADT as good as continuous ADT for men with progressive prostate cancer? The truth is that the studies done to date are flawed in a variety of ways and so we don’t have a definitive answer to this question either.

In our view, many of these “controversial” issues are absolutely not about black/white or right/wrong dichotomies at all. Rather they are about a whole host of factors that have to be considered in coming to optimal decisions, and about how the physiological, medical, and psychological profile of an individual man or patient and his family history affect risk and decision making for all concerned.

The intensity of these controversies is well exemplified by two articles in the September issue of the AUA News on the much discussed topic of who (if anyone) needs to be “screened” for risk of prostate cancer, and how this should be done. The articles are based on presentations at the annual meeting of the American Urological Association (AUA) back in May 2014.

On one side we have Dr. William Catalona, the arch-advocate for true, regular screening of all men at potential risk. Arguably, this would include every man between about 40 and 80 years of age. He takes the position that the American Urological Association’s 2013 guidelines on prostate cancer detection were misguided from day 1 and need to be revised immediately (although he doesn’t offer any particularly insightful suggestions about how to do that).

On the other side we have Dr. Ballentine (“Bal”) Carter, a senior author of the AUA’s guidelines, who emphasizes that the guidelines are constructed based on the best available evidence (as opposed to the opinions of “experts”, which all too often turn out to be rather less than “expert” after all) for men aged between about 55 and 69 years. Because these guidelines are evidence-based, they deliberately did not address protocols for risk assessment among subsets of men who are (probably) at elevated levels of risk but for whom there is no useful and truly data-based evidence suggesting screening either earlier or later.

The pros and cons of the two very different positions above-mentioned can be argued to the death, and that is not our intent here. These types of debate have been going on for decades with respect to all of the controversies identified above. We don’t expect any of them to be resolved in a definitive manner any time soon.

16 Responses

  1. What about the “controversy” of the long-term, negative effects of radiation therapies on the quality of life of prostate cancer victims.

  2. I’ve said in many posts that it will be yet another century or so before The Beast is under control and possibly curable for all. This article convinces me I am right. Many scoff at that notion but, then, it has been 110 years since the first radical prostatectomy for prostate cancer and, yet, here we are still unable to beat The Beast.

  3. Thanks for the clear demarcation of the issues re prostate cancer assessment of prevention, care and cure. Perhaps I’m reading too much into your comments, but the way you have framed them implies we really don’t know what specifically causes prostate cancer (other than generalized inflammation often of unknown causes). As such it appears you’re saying we really can’t prevent prostate cancer — with or without screening. At best we can slow it down or care or “cure” it after it manifests itself. I wonder if this is your thinking, or not?

    Also I wonder if your statement that the “… pros and cons … can be argued to the death” is a subconscious reference to one of the main worries we prostate cancer patients and survivors (and partners) all have, however overstated, in this order:

    (1) Will we survive or die? (Life or death.)
    (2) Will we be in pain or not?
    (3) Will we lose our vitality (and if so by how much?)?
    (4) How much will the intimacy between us and our partners be altered? (No pun intended.)

  4. Dear e.rosnow:

    That’s not a controversy. All treatments for prostate cancer have the potential for long-term negative effects. The only issue is one of degree in each individual patient. The long-term negative effects of radiation therapy can range from effects on urinary and erectile function to secondary cancers.

  5. Dear Rabbi Ed:

    We really have no idea what “causes” a man to get prostate cancer. In truth we have no idea why any particular cell mutates to become cancerous, and so to that extent we don’t know why anyone “gets” cancer. Thus, we clearly aren’t able to prevent prostate cancer because we don’t know why it occurs.

    Your second paragraph is clearly about things that have differing levels of importance to different patients. What I mean by that, as an example, is that I have actually never worried in the slightest about the question of whether I will survive or die of anything. I have a 100% certainty that I am going to die and I have every intention of being good humored about it when it happens (assuming I have any warning at all). However, I am well aware that others do worry about this … a lot … in relation to diseases of many types. What I can assure you of is that the statement about “… pros and cons … can be argued to the death” was absolutely not any type of subconscious reference to anything. It was a purely factual statement in the sense that some of those with strong opinions on one side or the other of specific controversies will, indeed, be arguing in favor of their opinion until their death relieves them (and perhaps the rest of us) of their ability to continue arguing for their belief.

  6. It’s a good summary which I will send to my two sons since I am stage pT3b Gleason 9 at pathology with no currently detectable prostate cancer after undergoing RP, ADT, and SRT. The sick thing about this disease is waiting for the rest of one’s life to see if it recurs and if so having to go through the next stage of treatment.

  7. Somewhere in the message should have been the consideration that despite the diagnosis of very early stage development of prostate cancer many patients will not need, and should not be encouraged to have, early invasive treatment options. Active surveillance, formerlly “watchful waiting,” continues a very important consideration for diagnosing/treating physicians and in that importance having researched and determined the appropriate continued diagnostics to be performed on a regular schedule, basic end points of those diagnostics that will determine when a move to invasive treatments becomes appropriate, and encouraging lifestyle changes for those patients whose current diagnostics indicate such changes might slow continued development of their early stage cancer.

  8. Dear Chuck:

    You seem to have overlooked the third bulletted point, which is entirely about the fact that many men don’t need immediate treatment (or sometimes any treatment, ever).

  9. No, Sitemaster, I didn’t fail to note that bullet point … rather I felt it necessary to elaborate the necessity of continued close attention by both physician and patient so that when development increases, both will know it is time to move to more definitive treatment to hopefully then nip further development, as well as eradicate, that now more prevalent prostate cancer.

  10. My experience so far:

    If your father dies of it, it should be on your short list of things to watch.

    Two years ago I started tracking my PSA using home tests I bought on the internet for US$30 or so each to supplement the very occasional ones I was getting from the clinic I use. I noticed it was gradually increasing above 4, and I was getting urinary hesitation, etc. The PSA eventually started to rise exponentially; when it reached 10 the doctor looked at me and said (in his least believable bedside manner) “You have cancer!” so I cast around for information and practitioners, absorbed several hospital sales pitches, found someone to do the biopsy (for you who don’t have that experience yet, it is a machine and procedure that would do a horror movie proud!); came back with a Gleason 4 + 4.

    That guy was pushing cryotherapy, which sounded like a bad idea to me, and/or prostatectomy, which didn’t delight me since the chatter was that it was a brutal operation which has the potential to make a real mess of things. So I went back to my semi-retired doctor at the clinic and he hooked me up with an IMRT guy who had some trick machinery; I asked my doctor how good he was, and he said “Everyone I have sent to him is still alive”; so on the basis of that I signed on. I’m 74, so I really could see bad sequelae from surgery, so the choice was pretty easy for me.

    He originally wanted to start with ADT, but my doctor opined that ADT never cured anything, and the cost of it was going to me several thousand extra dollars, so we skipped that part. Long story short, the treatment was uneventful, I did get a free PET scan as part of a research project, the side effects have been moderate and manageable, except I am now probably functionally impotent, but as a solution to the “sex or death” question, I guess it’s a fair trade.

  11. One of the oncologists involved in my treatment for high-risk prostate cancer (supposedly (!) localised), said the most he could honestly say, after the treatment was, “We think we got all of it.”

  12. SCREENING (Re “Who should receive regular tests (“screening”) for risk of prostate cancer and how?”)

    First, thanks for weighing in with this important list.

    This initial issue will strike many of us as the most important today. Personally, I’m convinced we have good enough answers to this question that balance the value of screening and avoiding over-treatment. The key is not in detailed pros and cons as the prospective screenee is typically not in a good position to absorb those, particularly considering the limits of time. (Renowned radiation oncologist Mack Roach of UCSF makes this point emphatically.) The key is whether the person considering screening is comfortable with the prospect of active surveillance (AS) for low-risk prostate cancer. That comfort level may not be initial, but be achievable after brief education on the mound of research supporting the success of AS for low-risk cancer. Assessing and supporting that comfort level should be a much simpler, comprehensible and briefer process than a discussion of pros and cons of various treatments to a patient that has not even been screened at that point!

    Armed with that awareness of the role of active surveillance, a screenee is in an excellent position to minimize over treatment should his screening result indicate the need for follow-up. With a well informed doctor, the screenee will also be able to make a good decision whether a biopsy is warranted, or just additional surveillance, and perhaps tactics other than treatment that appear to lower risk.

    Some men, together with their loved ones, will not be able to resist treatment once diagnosed, even after being informed about AS; they will not be able to seriously consider active surveillance and will therefore be likely to be overt treated. I believe most of men will be able to recognize whether they fall in this group in advance. To me, such men should probably skip screening, but perhaps with extra information about the risks of over treatment and prostate cancer.

    The rest, who are or who become comfortable with the value of active surveillance for appropriate cases, should be screened until age and comorbidities suggest screening would, on balance, not be worthwhile.

    The “how” of screening is another question. I am comfortable advocating that PSA should be the primary tool, but DRE screening is also important. Commencing screening at age 40 for screenees with a risk factor makes sense to me, even at 35 for high risk such as a couple of first degree relatives with prostate cancer that was diagnosed at an early age. Commencing screening at 40 to 50 for other men seems reasonable in view of current knowledge. Accumulating research is suggesting that some patients can skip a year or more of screening depending on a favorable baseline screen.

    My 2 cents.

  13. PREVENTION (“Re: Does ANYthing actually prevent prostate cancer?”)

    There is probably a consensus that we know of no agent (except for an early preemptive removal of the prostate) that has a high probability of preventing prostate cancer. There is probably also a consensus that well-structure clinical trials for potential preventive agents are typically very difficult to execute effectively, which means that definitive proof is very difficult to obtain. That said, there are other sources of attractive though inconclusive evidence that support some preventive tactics. I’m convinced we should inform people about such tactics.

    One key preventive concept is that overall diet appears to play an important role. Evidence of cancer incidence from following Japanese men who emigrated to the US and changed their dietary habits indicates that diet matters. Similarly, there is a lot of evidence, again inconclusive, that certain diets, such as the Mediterranean diet, are beneficial for prostate cancer as well as being beneficial for much greater threats to health (heart disease, for instance). Additionally, evidence for some specific nutrients, such as lycopene, appears favorable enough to warrant emphasis, especially in the context of negligible or no side effects. Also, on the drug side, why should we not inform people that long-term statin use is associated with less lethality from prostate cancer (but with some risk of side effects)? Regarding use of 5-alpha-reductase inhibitors, I’m not comfortable generally advocating use of finasteride or dutasteride at this time, but I think that time is coming based on fairly impressive effectiveness against low-risk prostate cancer coupled with enhancing detectability of more advanced disease, such as by reducing the “signal-to-noise” ratio in PSA testing and DRE exams.

    The agent that I find most exciting at this time is pomegranate, whether by juice or quality extract. We have now had at least three favorable clinical trials, though the UK trial included a mix of green tea, broccoli, and turmeric extracts as well as pomegranate.

    None of the agents mentioned above is a show-stopper for cancer, but all of them appear to have a substantial influence on risk, enough that they are worth talking about to people interested in prevention. That is the take-away point for me: we cannot offer conclusive evidence, but we have evidence enough to talk about prevention.

  14. Dear Jim:

    You are entirely entitled to your 2 cents, but please appreciate that others would utterly disagree with your fundamental premise that “we have good enough answers to this question that balance the value of screening and avoiding over-treatment.”

    For 25 years now I have taken an utterly different attitude to the issue because the risk for any cancer (not just prostate cancer) is utterly negligible in members of my family under the age of about 85. I have never had a PSA test unless it was required of me for health insurance purposes or because I had clinical symptoms of a urinary tract problem, and (as far as I am aware) my risk for prostate cancer continues to be negligible. In all honesty, at 66 years of age, I have little interest in discovering that I have a tiny area of Gleason 6 prostate cancer that would require active surveillance because the chances of such a diagnosis having any impact on my mortality is negligible. And as far as I am aware there is still no evidence of a diagnosis of prostate cancer among any of the men in my pretty extended family.

    My point is that “screening” for prostate cancer (however you want to carry it out) for a large proportion of the male population of America is an invitation to increase your risk for a variety of health-related problems (from simple stress from the diagnosis to actual unnecessary treatment). As I have said many times previously, if 1 in 6 men get diagnosed with prostate cancer in their lifetimes, that leaves the other 5 in 6 men with no such risk. Why would the 80% or so of the male population who are already at minimal risk want to modify that minimal risk by adding to it? That doesn’t seem like a wise approach to public health to me.

    Any individual man who wants to assess his risk for prostate cancer is more than welcome to do so after discussion with his physician(s); recommending that all men assess their individual risk for prostate cancer is something that I understand prostate cancer survivors are going to advocate for because of their own personal history and experience. My personal history and experience gives me a very different perspective … and I wouldn’t change my mind in the highly unlikely event that I got diagnosed tomorrow.

    That makes 4 cents in total!

  15. Dear Jim:

    No one is suggesting we shouldn’t talk about the possibility of prevention … However, without compelling data, what are you going to actually tell them to do beyond the fact that eating well and exercising regularly is good for nearly everyone — even that won’t actually stop any one individual from getting cancer.

  16. The comments are a great read! Thanks for a rigorous discussion.

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