The APCCC in Basel, Switzerland: Day 3


So today, the third day of the meeting, was “voting day” on a total of 123 questions carefully crafted by the organizers prior to the meeting. The questions had all gone through three cycles of review and revision prior to the meeting.

Nearly 60 recognized authorities on the management of advanced prostate cancer were empaneled to offer answers to the questions, and the entire cycle of questions and responses was electronically recorded.

Now your sitemaster could have simply photographed every set of questions and the answers as they were projected onto screens within the conference center. However, he did not do that. The reason he did not do that is that without the context of associated discussion that went on between the various sets of questions it would be impossible to truly understand the answers to all the questions, and it was beyond your sitemaster’s capabilities to take detailed notes on all those discussions and correlate the discussions to the specific questions and answers. It would also have taken up something like 25 pages of this web site and several days to write it all up.

However, …

The published report from this conference is going to be available in the very near near future, and that published report will include a precise report and analysis that encompasses all the questions and the answers given by panelists.

What your sitemaster can tell you at this time is the following:

  • The full report from the meeting will be an open access article, and so you will be able to read it all for yourselves.
  • The number of questions for which there was a true consensus (i.e., 90 percent or more of the panelists all agreed on one answer) was very small.
  • There were multiple questions, however, to which > 75 percent of panelists all agreed on one response.

There was just one truly controversial incident during the day, after panelists had responded to a question about the possible uses of different terms to describe men who had progressed after first-line androgen deprivation therapy. The term “castration-resistant prostate cancer” was one of the terms included in the options that panelists could select, and a significant number of panelists voted that this was the most appropriate term.

The other patient advocate present at the meeting, during discussion, was asked for his opinion on the use of this term, and he observed — in no uncertain terms — that in his opinion this was an offensive term that had long outlived its usefulness and that it was high time that it was replaced by a new term. If the other advocate had not said this, your sitemaster would have said something very similar.

It may well be that it is time to bring the terminology of advanced prostate cancer into the 21st Century. Terms like “castration-resistant” and “hormone-sensitive” (despite being widely used) are arguably both scientifically inaccurate and entymologically misleading. The term “androgen deprivation therapy” is accurate, but has come to be associated with only the older, first-line forms of treatment for advanced disease using bilateral orchiectomy or LHRH therapy, etc.

By contrast, a term like “androgen suppression therapy” or AST can be used to encompass all of the following types of of treatment:

  • Bilateral surgical orchiectomy
  • Medical orchiectomy (with an LHRH or a combination of an LHRH + an antiandrogen)
  • Antiandrogen monotherapy
  • Androgen receptor blockade (with a drug like enzalutamide, apalutamide, or darolutamide)
  • 17α-Hydroxylase/C17,20-lyase (CYP17) inhibition with abiraterone acetate + prednisone

All of these fiorms of treatment have the same fundamental intent: to lower the levels of androgens (like tetosterone, dihytrotestosterone, and others) that can directly or indirectly increase the risk for prostate cancer progression by stimulation of the growth of new prostate cancer cells.

This means that a patient can be accurately described as either AST naive or AST refractory before treatment with or after treatment failure on any one of multiple different forms of therapy, and it gets us away from the unfortunate historical “castration”-related terminology once and for all.

There is a preliminary plan in place to see if we can start the process of re-thinking the language of advanced prostate cancer. A lot of specialists in the field would like to see this happen — as would a lot of patients. It will take time, care, and patience. And some of the older terminology will inevitably remain in things like the prescribing information for specific drugs, but there is no reason why we need to go on using inaccurate terminology just because we have been using it for the past 40+ years.

FInally, your sitemaster wishes to state categorically that this was one of the best organized and most interesting “open” prostate cancer meetings it has been his pleasure to attend in most of the past 40 years. The meeting ran on time. The meeting site was well organized, clean, and comfortable. The attendees and the faculty were all fully engaged in the meeting (and in the networking opportunities available). And the meeting co-chairs, Dr. Silke Gillesen and Dr. Aurelius Omlin, did an absolutely superlative job of planning and overseeing the program and the process.

14 Responses

  1. I think they ought to follow the kind of nomenclature they use for staging (e.g., M1). Maybe using “H” to designate a catch-all “hormone therapy status”:

    — H0 = hormone therapy-naive or -sensitive (to GnRH agonist/antagonist, orchiectomy, mild anti-androgen (e.g., bicalutamide, flutamide, nilutamide), estrogen patch, or combination)
    — H1 first-line hormone therapy-resistant (to any of the above)
    — H2 = second-line hormone therapy-resistant (to abiraterone, enzalutamide, apalutamide, darolutamide, etc.)
    — H3 = third-line hormone therapy-resistant (to any two of the above)

  2. Sitemaster:

    Did the use of estradiol patches for ADT even come up?

  3. Thank you so much, Sitemaster, for recording and conveying the contents of this meeting; it is invaluable to many of us. And to find time to do all that during the meeting is remarkable, as those of you who attend meetings appreciate.

    Onward & upwards,

    rd

  4. Dear Bob: No. Actually I should point that out to the meeting organizers. Thanks.

  5. Dear Allen:

    There is actually an epistemological problem with that suggestions, which is that the only “hormome” therapies that have ever been used in the treatment of advanced prostate cancer are the estrogens — and most specifically DES. All other forms of androgen suppressive therapy have utilized either surgical methods or anti-androgenic agents, not “hormones” at all. The term “hormone” therapy is fundamentally misleading. However, I do agree with you that there needs to be a specific way to subcategorize the types of androgen suppression that are now available.

    Mike

  6. Sitemaster

    Thanks. The patches are a great alternative to LHRH agonists in terms of effectiveness, side effects, and cost. Men shouldn’t have to suffer under the likes of Lupron and it’s kin!

  7. Dear Sitemaster:

    One of the most comprehensive wrap-ups of any conference I have ever read. I commend your attentiveness and your ability to take sufficient notes/recordings to provide such detailed information.

  8. Sitemaster,

    Thank you for making this long trip to Switzerland to bring us the latest prostate cancer treatment news. You did a very nice job summarizing the findings. and we await the questions publication.

    As you have mentioned, the purpose of the meeting was to get the opinions of clinicians and experts in the field on various topics and previous research, rather than present new research.

    Some recurring themes in one’s reading about prostate cancer include: it is a unique cancer; something that we really don’t have a very good grasp on compared to other malignancies; we really don’t know what to do because clinical trials have not been run on these specifics, etc.

    What does this mean for the average patient? It could mean a patient may encounter difficulty getting cutting edge treatment that could help them because of costs; because their doctor doesn’t know about the new research or is willing to try it; etc.

    What is a patient to do? A prostate cancer patient or representative is well advised to get very familiar with the prostate cancer treatment literature so they can get an idea of what treatments might be potentially helpful and then start asking their respective clinicians questions about them. This is where this web site and others like UroToday.com and ClinicalTrials.gov can be so helpful, because they provide quality information that can be used as a starting point for this treatment search.

    The point is — the prostate cancer patient of today may need to be prepared to select a promising treatment before every last fact is in about it if they want to improve their chances of survival. Finding a real expert clinician would be at the top of the list of things to do as well. All this is not easy. Good luck!

  9. Mike:

    I disagree. By “hormone therapy,” we mean one which acts upon the AR axis — the therapy is directed at the hormones, not necessarily caused by hormones. (Just as a “metastasis therapy” is one which acts upon metastases,) No one would have a problem understanding this. I have yet to meet a patient who doesn’t understand that Lupron is a hormone therapy (because it suppresses testosterone production). No one thinks that Lupron itself is a hormone.

  10. Dear Walter:

    Actually I don’t see prostate cancer as unique at all compared to other forms of cancer. Similar things are happening across the entire cancer spectrum as we discover (rather unsurprisingly) that there are multiple forms of the majority of cancers. Your last two paragraphs, however, are very important. The more the individual patient is willing and able to learn and understand, and the better the expert he can find to help him in his treatment over time, the greater the opportunities that will or can be made available to the patient.

  11. Dear Allen:

    You are, of course, entirely entitled to your opinion. However, the fact that we have been using terms inappropriately for decades and people are used to them as a consequence is very different from whether the terms are correct and really “useful”.

    As an example, no one I am aware of uses the term “metastasis therapy” that you mention above. They use the (correct) term: “metastasis-directed therapy” (which has no implication as to the type of therapy given, only to the projected site of the effect).

    In the case of breast cancer, the most widely used “hormonal” therapy, tamoxifen, is appropriately referred to as a “selective estrogen receptor modulating” agent and women with breast cancer are all categorized over the course of their treatment as either estrogen receptor-positive (ER+) or estrogen receptor-negative (ER-) in terms of their ability to respond to estrogen modulating agents like tamoxifen. They are also classified similarly with respect to their responses to progesterone-modulating agents, as PR+ and PR-, and to HER2/neu expressing agents like trastusumab (Herceptin) as HER2+ and HER2-.

    Our methods for classifying prostate cancer patients, by comparison, have barely moved since the late 1970s, and it is high time that they did.

    Please understand that I don’t really care if we go on referring, casually, to a definable group of drugs as “hormonal” therapies for the treatment of certain types of prostate cancer, but what I do care about is that we get a much greater degree of accuracy that is highly relevant to individual patients and the forms of treatment that they may be appropriately be advised to use over the course of their cancer journey.

    Mike

  12. Hi Mike, Allen et al.,

    OK, I’ll jump into this discussion.

    According to the NCI’s web site, LHRH is a hormone. Here is what it says:

    “LHRH
    “A hormone made by a part of the brain called the hypothalamus. LHRH causes the pituitary gland in the brain to make and secrete the hormones luteinizing hormone (LH) and follicle-stimulating hormone (FSH).”

    Thus the LHRH agonists, like Lurpon and Zoladex, are hormones, albeit synthetic ones.

    However referring to standard ADT with LHRH drugs (be they agonists or antagonists) as “hormone therapy” is confusing to many patients. Some time ago a medical student and I published on that and here’s the reference:

    Rot I, Ogah I, Wassersug RJ. The language of prostate cancer treatments and implications for informed decision making by patients and their partners. Eur J Cancer Care. 2012; 21:766-775

    Would the “other patient” representative at the Basel meeting, who wanted the word “castrate” to be expunged from urology, be willing to correspond with me about what he sees as a better term? I would like to know what term(s) he feels might be better, when the term “hormone therapy” suffers from vagueness.

    Please let him know that I come at this as an academic, who has thought a bit about the language around prostate cancer and hopes to write more on the topic.

    Yours truly,

    Richard W.

  13. Mike:

    Symbols are neither correct nor incorrect, they are just placeholders. “N1” means there have been cancerous pelvic lymph nodes detected. The “N” is just a consensual convention. T4 means the cancer has infiltrated nearby non-prostate tissue. “T” means stage because we say it means stage. An H attached to a diagnosis represents whatever a consensus wishes it to mean. If we wish “H1” to mean “resistant to first-line androgen axis therapy” then that’s precisely what it means.

  14. Dear Richard:

    The “other advocate” is Robin Millman, who lives in the UK. You will see that he has already expressed an opinion above. I believe I am correct in stating that Robin’s priority is elimination of reference to the term related to “castration”, and that he is less concerned about other terms.

    There are actually two quite different issues related to all of this. One related to “colloquial” terminology — as might be used between a physician and his/her patients, when the use of a term like “hormonal therapy” might stull be entirely appropriate. The other is the increasingly precise terminology that is becomming essential in the scientific literature, and which, in my perception, needs a major overhaul. Either way, getting rid of the term “castration” is the priority that Robin and I (and many others in the patient community) are focused on in the shorter term.

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