Primary ADT ineffective for most men with early stage prostate cancer


Data from a large, retrospective study, reported in the Journal of Clinical Oncology, suggest something that many expert clinicians and patients have long suspected … that early use of androgen deprivation therapy (ADT) alone is not an effective treatment for most men with early stage prostate cancer.

The abstract of the paper by Potosky et al. is available on line, and can be supplemented by information in a media release from Georgetown University Medical Center in Washington, DC, and a report on the MedPage Today web site.

Potosky and his colleagues based their study on registry and utilization data for patients newly diagnosed with prostate cancer at any one of three large, integrated health plans. All patients were initially diagnosed between 1995 and 2008; none of them were treated with curative intent; and patients were all followed up though December 2010. The primary outcome endpoints were all-cause and prostate cancer-specific mortality.

Here are the core findings:

  • The data set included 15,170 patients.
    • 3,435 patients (22.6 percent) received primary ADT.
    • The remainder were all managed initially with either active surveillance or watchful waiting.
  • Compared to the men managed with active surveillance or watchful waiting, the men treated with primary ADT were
    • Older
    • Had higher baseline PSA values
    • Were more likely to have a Gleason score ≥ 7
    • Were more likely to have a clinical stage ≥ T2b disease at diagnosis
    • Were more likely to meet American Urological Association criteria for intermediate- or high-risk disease (as opposed to low-risk disease).
  • Among the primary ADT group,
    • 49 percent of patients died during the follow-up period.
    • 13 percent of patients died of prostate cancer during the follow-up period.
  • Among the active surveillance/watchful waiting group,
    • 28 percent of patients died during the follow-up period.
    • 5 percent of patients died of prostate cancer during the follow-up period.
  • After adjustment for relevant sociodemographic and clinical characteristics, the use of primary ADT
    • Was not associated with risk for all-cause mortality (hazard ratio [HR] = 1.04)
    • Was not associated with risk for prostate cancer-specific mortality (HR = 1.03)
    • Was associated with decreased risk for all-cause mortality
    • Was not was associated with decreased risk for prostate cancer-specific mortality
    • Was associated with decreased risk of all-cause mortality among the subgroup of men with a high risk of cancer progression (HR = 0.88)

The authors conclude that

  • There was no mortality benefit associated with primary ADT compared to no primary ADT for most men with clinically localized prostate cancer who received no treatment administered with curative intent, but
  • Men with higher-risk, clinically localized prostate cancer may derive a small clinical benefit from primary ADT if they have had no other treatment administered with curative intent.

The implication is that the majority of men who are not considered suitable candidates for early treatment with curative intent may be better off if the use of ADT is deferred (through the use of active surveillance or watchful waiting) until there is good reason to treat the cancer later, at early signals of the presence of evidence of metastatic disease or to alleviate other symptoms of progressive disease. ADT might be appropriately used earlier in men with D’Amico high-risk disease who are not considered suitable candidates for initial treatment with curative intent.

Quoted in the media release from Georgetown University Medical Center, Potosky states that:

Given the aging American population, more men are likely to be faced with prostate cancer so its is very important to understand the whether the risks of primary androgen deprivation therapy outweigh the survival benefit.  … Ultimately, this is a decision for men and their doctors to make together, and we hope that our study provides some helpful information to guide these decisions.

Quoted on the MedPage Today web site, Dr. Charles Ryan of the University of California, San Francisco, stated:

There has been a historical assumption that use of primary ADT would be something that would control the cancer in men who don’t want surgery or radiation therapy. I think, in many cases, [primary ADT] was done without a lot of thought.

I don’t think this will impact somebody’s decision to do active surveillance. … I think it should impact clinicians’ decision to use hormonal therapy in lieu of local therapy in patients who do choose active surveillance.

The research team is currently using data from the same 15,000+ patient to investigate rates of potential side effects associated with the use of primary ADT in treatment of early-stage prostate cancer.

[Editorial note: This commentary has been updated as of 7:45 a.m. on March 18 compared to the original information initially posted late on March 17, 2014.]

18 Responses

  1. Makes one wonder about the ancient and flawed models used in the past to associate prostate cancer with testosterone. …

  2. USE OF SINGLE AGENT THERAPY?

    A number of those of us who, like me, are fans of ADT, including primary ADT in appropriate patients, are not at all impressed with single agent therapy (or orchiectomy), and we are not that impressed with combined LHRH-agonist/antiandrogen therapy either, though that seems much more effective than single agent therapy. I credit IADT3 with helping me survive in pretty good shape with a challenging case now at the fifteenth year point. (Had a curative attempt with radiation last year.)

    I’ve read both linked pieces, and neither indicates the type of ADT. Given the time frame, it is reasonable to suspect that many if not most of the patients were on single agent blockade. I’ll bet very few were on ADT3. I’m wondering if the critical details of the types of ADT are presented in the paper. I’m also wondering whether the use of countermeasures for side effects was addressed in the paper. When the team looks into side effects, they had better also address countermeasure use and impact or their product will be seriously limited in its applicability!

    I suspect the authors are over generalizing to all ADT when their data are probably pertinent only to single agent, or at most double agent ADT.

  3. Dear Jim:

    I am quite sure that the authors included all types of ADT in this paper, and very deliberately. You are also likely to be correct that for most of those patients what was being used was either single-agent or two-agent therapy. I haven’t seen the entire paper, so I have no idea whether the authors were able to tease out the types of ADT being used. However, your follow-up comments are not as easily justified because we have no reliable data from any large study (whether prospective or retrospective, let alone randomized and double blind) to demonstrate that IADT3 actually has a survival benefit compared to any other form of ADT. That is an article of faith among the advocates of this type of treatment. I would point out that there are also patients who have lived for 10+ and 15+ years on single-agent and dual-agent forms of ADT.

    Please understand that I recognize that there appear to have been benefits associated with IADT in a very small number of very highly motivated patients like you and Chuck Maack. However, that is no proof that IADT3 would work for most men. Furthermore, Chuck Maack would not have met the entry criteria for this study, and you met the high-risk criteria.

    With respect to the proposed analysis of the side effects of the therapy, it is actually irrelevant whether countermeasures were being used or not. Why? Because if the patients should never have been on ADT in the first place, then the relevant issue is how much they were being harmed by the adverse effects of a treatment that was inappropriate to begin with, not whether the side effects of the ADT could have been ameliorated.

  4. Dear Walt:

    I am not at all sure what you are implying by your comment above. There is a very strong general association between serum testosterone levels and the progression of prostate cancer over time.

    The places where there is still a lack of clarity are: (a) whether men with “high normal” testosterone levels are at any greater risk for an initial diagnosis of prostate cancer than men with “low normal” levels; (b) whether testosterone supplements necessarily increase risk for disease recurrence among men who have had apparently curative treatment for their prostate cancer; (c) whether intermittent testosterone supplementation necessarily increases risk for disease progression among men being treated with intermittent ADT; and (d) whether testosterone supplementation may be appropriately used in men who have low serum T levels after long-term continuous ADT.

    What seems to be increasingly likely is that there are additional factors that impact this risk. For example, testosterone supplementation may be less risky for men initially diagnosed with true Gleason 6 disease, since true Gleason 6 disease is associated with a very low risk for metastasis anyway, whether treated or not. By contrast, my suspicion is that a man who was initially treated with radiation + 3 years of ADT for high-risk prostate cancer with a Gleason score of 8-10 and perineural invasion and who is still in biochemical remission after 5 years is likely to be taking a very considerable risk if he initiates testosterone supplements. If he wants to take that risk in consultation with his doctors, that’s his decision to take, but it would be delusional to think there was not a very considerable risk associated with such a treatment.

    We are still at the very earliest stages of beginning to work out which patients are really good candidates for testosterone supplementation after first-line and follow-up therapies. While this seems to be safe in some patients, we do know that it is strongly associated with disease recurrence in others. On the other hand, it seems to be increasingly evident that a man’s “normal” serum testosterone level is not specifically associated with his risk for prostate cancer, but what may actually be more important than the serum testosterone level is the levels of testosterone and dihydrotestosterone within cells in the prostate (the microenvironment), which are a lot harder to measure than levels in the circulating blood.

  5. Sitemaster:

    I am an accolade of Dr. Morgenthaler’s school of thought. No point in re-stating it here, his work is widely available for all to read. as for my comments above, they obviously apply to non-metastasized prostate cancer.

    Interestingly enough, some of Dr. Morgenthaler’s research indicates low testosterone as more of a statistical indicator for prostate cancer, than normal or slightly elevated T. Considering that if we all lived to 100, almost all of us would get prostate cancer, I find that all rather logical.

    Thanks for this excellent and informative site!! :)

  6. Hi Walt — replying to your 3/18 of 8:10 am:

    The docs I follow closely are generally concerned with a finding of low testosterone but advanced prostate cancer because it suggests the cancer has found a way to thrive with a low level of T, and that often indicates androgen deprivation therapy will not be as successful as is typical.

  7. You are speaking of metastasized prostate cancer, no?

  8. Walt:

    No. There are lots of men with localized disease — particularly older men who are not good candidates for surgery or other forms of primary therapy — who get treated with primary ADT.

    What is really happening here is that their doctors are “managing their patients’ PSA levels”. This has no long-term survival benefit as far as we can tell and so the patients suffer all the side effects of ADT but get no long-term benefit. Most of these patients would do just as well (if not better) to delay initiation of ADT until they really needed it, e.g., when there is very early evidence of actual metastasis, when there are actual symptoms of disease progression that needed to be managed, or when their PSA levels get to a point that treatment really is advisable (e.g., something like 50 ng/ml or above).

  9. Wow, that sounds awful; ADT with no benefit, and all the harm. (Shudders!)

  10. Walt:

    This (in my humble opinion) is a direct consequence of something Dr. Klotz mentioned yesterday — the societal response to the statement “You have cancer.” Most of these men may well have some cancer cells, but just how many of them have clinically significant cancer that really needs treatment is a whole different issue. And even if they do have significant cancer, it can be managed perfectly well with ADT much later (if necessary).

  11. WHAT TO DO WITH ADT IN ABSENCE OF TRIALS THAT WOULD CLARIFY USE OF ADT2, ADT3 AND TIMING (INTERMITTENT USE ALREADY CLEAR)

    Hi Sitemaster. As always, thanks for finding interesting studies and providing thoughtful comments. I’ll post several points here and separately that are in contrast to the thrust of the paper and your review including your response of March 18, 2014 at 7:17 am to my earlier post of March 17, 2014 at 10:31 pm “USE OF SINGLE AGENT THERAPY?,” and I hope you won’t mind a little tongue in cheek tone to these thoughts that are meant to advance the dialog. To recap the bidding, this paper and your comments reflect this general view of ADT, I believe:

    (1) USE FOR EARLY STAGE PROSTATE CANCER: “… that early use of androgen deprivation therapy (ADT) alone is not an effective treatment for most men with early stage prostate cancer.”

    (2) RISKS OF HARMS AND BENEFITS: “it is very important to understand whether the risks of primary androgen deprivation therapy outweigh the survival benefit.”

    (3) SCARCITY OF DATA SUPPORTING IADT3 COMPARED TO SINGLE AND DOUBLE AGENT ADT: “However, your [meaning me, Jim] follow-up comments are not as easily justified because we have no reliable data from any large study (whether prospective or retrospective, let alone randomized and double blind) to demonstrate that IADT3 actually has a survival benefit compared to any other form of ADT.”

    (4) DEFERRING ADT VERSUS ADT EARLY: “The implication is that the majority of men who are not considered suitable candidates for early treatment with curative intent may be better off if the use of ADT is deferred (through the use of active surveillance or watchful waiting) until there is good reason to treat the cancer later, at early signals of the presence of evidence of metastatic disease or to alleviate other symptoms of progressive disease.”

    (5) RELEVANCE OF COUNTERMEASURES WITH ADT: “With respect to the proposed analysis of the side effects of the therapy, it is actually irrelevant whether countermeasures were being used or not. Why? Because if the patients should never have been on ADT in the first place, then the relevant issue is how much they were being harmed by the adverse effects of a treatment that was inappropriate to begin with, not whether the side effects of the ADT could have been ameliorated.”

    (6) PENDING REPLACEMENT OF SOME ADT TACTICS WITH FAR IMPROVED FORMS OF ADT (NOT ADDRESSED IN PAPER OR REVIEW).

    Regarding issue (1) USE FOR EARLY STAGE PROSTATE CANCER, I’m rethinking that maybe it is wise, as the paper suggests, for men whose doctors would use only single therapy, such as an LHRH agonist drug (e.g., Lupron, Zoladex, Trelstar-LA, Viadur) or an orchiectomy, to avoid ADT for early stage prostate cancer as, in view of the knowledge that is now available, use of a single agent strikes me as suggesting the doctor has not kept up. Such a doctor would probably: not consider or know how to implement active surveillance as an alternative to ADT for a truly low-risk patient, based on a still increasing but now large and convincing body of research favoring active surveillance as a safe and effective approach for low-risk patients; not monitor testosterone, DHT and perhaps other markers; not see the potential problem for a large proportion of men, I think, of a PSA with a low point (nadir) above 0.05; not even be using an ultrasensitive test capable of reliably detecting PSA below 0.1 to at least as low as 0.05; not understand the need to ensure, based on the foregoing tests, that delivery of the drug was proper (e.g., not into fat vice muscle for Lupron; no coil slipping out for Zoladex; proper storage and mixing; etc.); neither appreciate the need or know how to adjust the dose for the subset of patients who clear the drug significantly faster than anticipated in the dosing guidance; and not realize for most men when a second or second and third agent were also needed; not realize that many men with severely decreased production of testicular testosterone would be very likely to face some of a syndrome of side effects, of varying degrees of severity and danger, depending on the individual; not understand that those side effects could often be substantially ameliorated by countermeasures, and therefore not advise their patients about those countermeasures. These doctors would be like the ones who told me in the early 2000s and so many others of us in later years that ADT works only for 18 to 24 months, not realizing that those numbers were from already obsolete studies in the 1990s on men with widespread bone metastases, with results for men with earlier stage disease extremely likely to be far superior. No, for a patient with apparently early stage disease with such a doctor, I too think single agent ADT would not be wise.

  12. Regarding issue (2) RISKS OF HARMS AND BENEFITS, again I’m rethinking this based on the paper’s likely effective emphasis on single blockade that the harms, for single blockade, do outweigh the benefits for most men. After all, the medical oncologists with large practices dedicated just to prostate cancer, thereby seeing and regularly getting feedback from diligent monitoring of a large body of patients, don’t care much for single blockade.

    They have pointed out for years that the adrenal gland is quite capable of producing testosterone indirectly, and that this gland ramps that production up, considerably up in some men (even up to 40% of normal — far, far more than enough to circumvent blockade) when it senses through the hormone feedback system that there is a shortage of testosterone. Those doctors with large dedicated practices have also noted that dihydrotestosterone (DHT) is a much more devastating fuel for prostate cancer growth than testosterone, and, while made from testosterone, it too often remains at an almost normal level even when testosterone is sharply reduced. That doctor who assumes single agent therapy is just fine is unlikely, I suspect, to be monitoring DHT (heck, he’s probably not monitoring testosterone either), so he is not going to see the need to use a second drug, an anti-androgen to help block DHT from docking as fuel at the androgen receptor docking ports on the cancer cell, nor will he appreciate the value of using a 5-alpha reductase inhibitor drug (5-ARI) to sharply curtail the conversion of DHT from testosterone.

    Therefore, it is reasonable to see that single agent blockade for men who really need to cope with aggressive cancer will have limited benefit for many of them. So, yes, the harms probably do outweigh the benefits of single agent ADT for many men, perhaps most or even the vast majority, which is probably why the doctors with large medical oncology practices dedicated to prostate cancer do not like single blockade much. Of course, they do see a large therapeutic index (benefit to harm ratio) advantage for double and especially triple blockade, but that brings up issue (3), which I’ll post about separately. But the critical point here is that results of benefits and harms of single agent therapy do not match those for double and triple blockade, so the indictment of single blockade really does not apply to those other forms! I doubt very much that this study has much of worth to contribute about those forms of blockade.

    As for evidence, I have a complete copy of a Japanese study I found most interesting that looked at a variety of forms of ADT done in Japan as primary therapy. The numbers for each type are large, as there is much greater cultural/physician acceptance of primary ADT in Japan than in the US and Europe. Here’s the citation, with a link to the abstract: Hinotsu S, Akaza H, Usami M, Ogawa O, Kagawa S, et al. Current status of endocrine therapy for prostate cancer in Japan analysis of primary androgen deprivation therapy on the basis of data collected by J-CaP.Jpn J Clin Oncol. 2007;37(10):775-81. [The full text is supposedly also available on line, but your sitemaster has been unable to find it so far.] The review was pretty comprehensive as to types of ADT: “… initial therapy was divided into eight categories:

    — anti-androgen monotherapy
    — surgical castration only
    — LHRH agonist monotherapy
    — LHRH agonist + short-term anti-androgen
    — surgical castration + anti-androgen*
    — LHRH agonist + anti-androgen*
    — watchful waiting;
    — other

    The two asterisked categories are defined as maximal androgen blockade (MAB). The categories “watchful waiting” and “others” were excluded from part of this interim analysis of prognosis because the number of patients assigned to these two categories was too small. The study population involved patients newly starting ADT for prostate cancer from 2001 through 2003 and was from many institutions nationwide. Figure 1 shows the numbers and proportions for each approach, with LHRH + AA (LHRH agonist plus an anti-androgen that was not short term) being dominant with 53.8% (10,434/19,409 cases), with LHRH agonist + short-term AA use coming in second at 24% (4,673/19,409). ADT3 was not covered.

    I was stunned in 2007 by what I saw in Figure 6, which has progression-free survival curves for men with Stage II, Stage III and Stage IV cancer. For Stage II, surgical castration + AA comes out best at the 5-year point at about 70% success, with other approaches splayed out down to about 45% for LHRH + short-term AA and LHRH agonist alone about 5 points better. The differences are certainly clear, but not especially striking.

    However, for Stage III, there are three very distinct and widely spaced outcomes at slightly beyond 5 years: surgical castration plus an anti-androgen continues to look good and is distinctly superior at 70% success, even for Stage III. Several other approaches are rather closely bunched around 40% to 45% success, but the one straggler, way below, is LHRH agonist therapy alone at slightly above 10% success! It does okay up to about the 5-year point but then simply falls off a cliff! As I said, I’m not much impressed with single therapy for the men who really need ADT.

  13. Dear Jim:

    So after an extensive search I have been unable to find a link to the full text of this article. However, primary ADT in the context of the current discussion refers exclusively to the treatment of men with no metastases who have had no prior therapy whatsoever. Can you confirm that that is the case for the men in the Japanese study? Better still, can you provide an actual link to the full text of the paper? Your conclusions do not seem to correlate to the statements made by the authors in their abstract.

  14. @JIM WALDENFELS I know very little about this subject, so all I can do is report about an article. I think I have it but have not read it, so what I shall now say might well be wrong. If memory serves, the paper concerns the molecular structure of testosterone receptors on prostate cells. There seem to be two ways for testosterone to enter a cell through these receptors. One responds to ADT, but often shuts down after a period. The other allows testosterone to enter via another pathway and via another molecular structure within those receptors, or a change in existing structures, perhaps protein folding. Now, if this is true, it would go some way towards explaining why ADT fails after some period, in almost all cases. Namely, at first ADT blocks both entry pathways; when ADT fails, one is blocked but the other opens. Or something like that.

  15. LINK TO THE JAPANESE STUDY

    Hi Sitemaster,

    This is weird! I just clicked the link above that takes us directly to the abstract on PubMed, and it has its usual link to a free copy of the study near the upper right corner. I would blame sunspots.

    Here’s a direct link to the paper on the Oxford Journals site.

    I just tried it, and that too worked for me.

    I reread the abstract and verified your observation that the abstract did not match my comments, specifically the line in the abstract stating: “In progression-free survival, the prognosis was slightly better following maximum androgen blockade (MAB) in each stage.” All I can say is that the term “slightly” appears to have a different meaning in Japanese- English dictionaries than in common English usage! LOL

  16. Dear Jim:

    Thank you for the link. Maybe it was sunspots or maybe I am just going blind as well as senile!

    Having read carefully through the paper, I have to say that I really don’t think it supports your arguments at all. Over 6,000 of the patients were stage IV at time of diagnosis, and one has to assume that at least half if not most of those men had metastatic disease at diagnosis, so they aren’t comparable to the men in the US study discussed above.

    Futhermore, even the authors of the study state clearly that their data, in almost all of the subset analyses, are either not statistically significant or at best show a trend toward significance.

    While I understand your desire to find data that support your perspective, I would respectfully submit that “seeing what one wants to see” and statistically significant data are two very different animals.

    By comparison, the US study reported above provides a clear indication that the only benefit for primary ADT vs. active surveillance or observation/watchful waiting followed by ADT when needed was in men with high-risk disease at diagnosis.

    Although I haven’t been able to see if this paper breaks down the data by type of ADT, my guess would be that the subset analysis would also be based on groups too small to permit a sound statistical analysis.

  17. Hi Sitemaster:

    I’m responding to your comments of March 23, 2014 at 7:18 am on the Japanese study that I described. I remain convinced that this study suggests a strong impact of combined versus single blockade, but I never meant that combined blockade made a major difference where it was not needed (low-risk patients, using Stages 1 and 2 as a proxy for low-risk as this study discusses risk groups primarily by stage) or where the cancer was quite advanced (Stage 4 patients in this paper), a situation where ADT helps but is of limited effectiveness in delaying progression, as has been well established by many studies.

    The key to understanding is to see that well done ADT makes a difference at the “sweet spot” — neither too low in risk nor too advanced. That’s what the doctors I consider experts in ADT have been advocating for a long time. That’s what is so meaningful about the figures that show progression-free survival results for Stage III prostate cancer by type of ADT. Yes, looking at the whole Japanese study and merging risk groups, that sweet spot activity is muted so that it does not look that impressive, and I believe that situation, echoed in other studies and in clinical experience, is misleading doctors from the true effectiveness of combined and especially triple therapy where it is most appropriate: in men who are beyond low-risk, such as recurring and typical intermediate- and high-risk cases that are not yet castration resistant and/or metastatic.

    As for breaking down data by type of ADT, I’m seeing this very clearly as a long-time veteran of ADT who has followed the topic closely. The following three types in the paper are single agent blockade:

    — antiandrogen monotherapy
    — surgical castration only
    — LHRH agonist monotherapy

    The second and third are the much more standard approaches, either orchiectomy or drugs like Lupron, Zoladex, Trelstar LA or Viadur, and the first is much less used ADT using drugs like Casodex (bicalutamide), flutamide, nilutamide (or now enzalutamide [Xtandi], a far more potent antiandrogen which was not available until well after this study). Though the antiandrogens (prior to Xtandi) have not proven that effective in controlling cancer compared to the other two approaches, antandrogen monotherapy (or with a 5-alpha-reductase inhibitor [finasteride or Avodart]) has proven useful in patients where the cancer control/side effect minimization balance tips more toward side effect minimization.

    The following types are combined ADT:

    — LHRH agonist + short-term anti-androgen
    — surgical castration + antiandrogen*
    — LHRH agonist + antiandrogen*

    The first type is much more like monotherapy as the antiandrogen is used very briefly to prevent the “flare” phenomenon: an initial surge of testosterone due to an LHRH agonist. The second and third types both combine shutting down testicular production of testosterone with at least partial blocking of the androgen receptor ports on the prostate cancer cells. 5-ARI drugs like finasteride and dutasteride make that blocking a lot more effective by sharply reducing the potent dihydprotestosterone (DHT) that is much more effective as an androgen than PSA in bullying its way in to the docking ports, often shoving the antiandrogen drug out of the way so it cannot block the ports. However, 5-ARIs were not used in this study.

    By the way, I am now very near the end of my experience with ADT, I hope. I’m in my 17th month (out of 18 planned months) of triple ADT (Lupron, flutamide, Avodart, with Vivelle estrodiol patches, Ursodiol, and 40 mg of simvastatin in support, as well as supplements and lifestyle tactics). In this, my fourth round and fifteenth year of triple therapy for my challenging case, my PSA a couple of weeks ago had continued to fall to 0.02 ng/ml, the fourth time I have reached that level or lower, but this time in support of a hopefully curative course of TomoTherapy IMRT radiation at this time last year.

    I hope to follow up the other issues I identified in my earlier post.

  18. REGARDING LACK OF “SIGNIFICANCE” IN RESULTS

    Hi again, deja vu here, in responding to your comments of March 23, 2014 at 7:18 am on the Japanese study, particularly your observation that “even the authors of the study state clearly that their data, in almost all of the subset analyses, are either not statistically significant or at best show a trend toward significance.” This is clearly one of those instances where it pays to look at the graph and not just consider summary statistics.

    Like the river that slopes down to a depth of 100 feet but averages a depth of 10 feet, a statistic that counts various time points and averages them in a trend will not show the stunning, fall-off-the-cliff pattern of cancer progression for the 484 men on LHRH-agonist monotherapy (the black line) for Stage III cancer at the five year point.

    Those patients do fine (meaning running in the pack (at about 40% freedom from progression but continuously falling success at 5 years, though far below the results for combined ADT using surgical castration + antiandrogen – the light blue line with a five year plus success mark somewhat above 70% and flat for a year, not declining since year 4!), until they come to that five year check point: that’s where those LHRH-agonist only patients plunge off the cliff in comparison to all the other approaches, with only 15% not showing cancer progression. PubMed has been acting up tonight, and I haven’t been able to check for a followup study, but I’ll bet the AA monotherapy and short AA + LHRH agonist groups will follow the LHRH-agonist monotherapy group by years 6 or 7, with the combined therapy group continuing to do fairly well. I know that’s speculative, but I’m just staking out a position.

    If I were a Stage 3 or advanced but non-metastatic, hormone therapy “naive” (never before on ADT) patient choosing an approach based on the data in Figure 6, I would sure as heck would NOT want to be in that black line LHRH-agonist monotherapy group!

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