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Medical Forum / Diseases and Disorders / Prostate Cancer / May 2006COMMENTS FROM VANDERBILT ONCOLOGIST
After my PSA went fro .67 to 1.1 [ran test again a week later and it was .93] in 3 mos., yesterday I saw Dr. Bruce Roth at Vanderbilt in Nashville. Roth was formerly at Indiana, treated Lance Armstrong, is a member of ECOG, etc. He follows the traditional thinking in every respect (and rejects Strum, et al.): 1. Androgen dependent PCa does not mutate into androgen independent PCa; i.e. there are 2 distinct cell populations from the get-go; 2. HT only affects the ADPC and, thus, the AIPC continues to grow and eventually predominates; 3. There is not a perfect correlation between PSA level and tumor load; i.e. PSA can rise w/o a corresponding increase in PCa volume, and vice versa; 4. Do not treat the PSA - treat the PCa; i.e. extent of disease and effectiveness of Tx are often more accurately gauged by factors such as time to recurrence, PSADT, etc.; 5. SRT is rarely effective in cases w/ seminal vesicle involvement; 6. There is no proven benefit of early over late HT; 7. Intermittent HT does not work as well as continuous. (he says there will be a European study released in the next few days/weeks showing this.); 8. Combined HT offers no benefit over Lupron monotherapy; 9. Large % PSA changes below 1.0 are not necessarily ominous. In my case he agreed 100% w/ my evaluation that I had systemic disease at the time of Dx because of SVI and 33 PSA and that SRT was contraindicated. He said there was no reason to rush into HT now - he wants me to continue to get quarterly PSAs and not do anything until it doubles in a relatively short time - 3-6 mos. He says that he has seen men go for years of PSA increases w/o clinical sysmptoms and, e.g., dozens of pleural mets dissappear upon initiation of HT. He was impressed that I have gone over 4 years and PSA still below 1.0. The good news was that I need not do anything now and that I can still live a long time w/ this disease, but the bad news is that I am ultimately doomed by it unless something else gets me first. Bill Denton RP 2/12/02 PSA .93 Memphis > After my PSA went fro .67 to 1.1 [ran test again a week later and it > was .93] in 3 mos., yesterday I saw Dr. Bruce Roth at Vanderbilt in [quoted text clipped - 31 lines] > a long time w/ this disease, but the bad news is that I am ultimately > doomed by it unless something else gets me first. Or someone comes up with a cure for advanced prostate cancer. > Bill Denton > RP 2/12/02 > PSA .93 > Memphis > After my PSA went fro .67 to 1.1 [ran test again a week later and it > was .93] in 3 mos., yesterday I saw Dr. Bruce Roth at Vanderbilt in [quoted text clipped - 4 lines] > 1. Androgen dependent PCa does not mutate into androgen independent > PCa; i.e. there are 2 distinct cell populations from the get-go; Bill, You should be very careful about taking opinions as fact. Biologically, it has been shown that the androgen dependent PCa cell line LNCaP can be changed to androgen independent simply by increasing its production of bcl-2 (which protects the cell against apoptosis). Therefore, any androgen dependent PCa cell has a chance to become androgen independent every time it divides. However, it is reasonable to say that such mutations will not occur as a result of ADT. I.e., those cells that have enough bcl-2 (or other mutations that protect against apoptosis) will survive ADT, and those that don't will die (they won't magically change their genetic makeup in order to survive). Statistically speaking, the more total PCa cells you have within you the greater the chance that some of those cells will be resistant to ADT. Now, this does not mean that you should jump into ADT early in order to prevent the development of mutations that will produce AIPC. Recent research on LNCaP transplanted into mice showed that intermittent ADT followed by testosterone plus finasteride was ~5 times more effective than continual ADT (http://www3.interscience.wiley.com/cgi-bin/abstract/112221624/ABSTRACT). However, even though that treatment worked with LNCaP, my model indicates that there are some extremely rare mutations in which such a treatment would be harmful (and, of course, the more total cells you have the more likely that you have such a rare mutation). Ed Friedman Ed: I was wondering if and when you were going to weigh in on this one. Interesting discussion nevertheless. B.A. Bill, Good luck in your fight. Keep your immune system strong. Your holding this disease off where I stand. There will be a cure before it can get to you. You got guts man. Good luck. Dave P Bill related several points I find encouraging and supportive yet contradictory with other data: > Dr. Bruce Roth . . . rejects Strum, et al.) Did he say why? Many of us all but idolize, and base decisions on, Strum just because his is the most detailed analysis we have of ADT. OTOH, my uros, along with whole bodies of uros, also suspect or outright even reject his work, so Roth is not alone. > 5. SRT is rarely effective in cases w/ seminal vesicle involvement A newly published study mentioned here weeks ago pegs the benefit of SRT w/SVI at 30%. I wonder whether Roth is unfamiliar with that study or just doesn't buy it/ > 6. There is no proven benefit of early over late HT Another recent study denies that after years of studies supported that position, raising the same question. Roth's remaining points fit the mold I've seen before. Thanks for this enlightening and overall personally reassuring summary. I.P. Ed, I did not present any of that as fact - I simply stated it as comments from a prominent oncologist who follows the traditional thinking. I believe I am correct in saying that this is a decent summary of the traditional view and is what most of us will hear from the majority of oncologists (and Walsh/Johns Hopkins-ist uros) that we see. Frankly, I was somewhat dissappointed that he gave the party line and didn't seem very open to other approaches. However, unlike some doctors who just blindly go w/ the flow, this guy does have reasons for his rejection of novel theories and treatments. If you don't mind, I would like to send him a summary of your model - where can I find a succinct statement of it? I.P., all you have to do is look at what he believes and you will see that it is contrary to Strum. Strum basically believes that ADPC does somehow naturally change into AIPC over time. [When I asked him on the P2P site to clarify his theory I got a reply from the moderator that he was refusing to discuss it further. Hmm.] Thus, it is imperative to kill off as much of the PCa as possible as early as possible w/ HT because the no. of mutations or genetic shifts from ADPC to AIPC will be reduced. Theoretically you go much longer before going refractive. This has logical appeal to me but the published studies just haven't borne it out. Although we did not discuss Strum personally, I think he would characterize Strum as a micromanager of insignificant lab statistics - constantly adjusting this and that to increae or decrease levels of things that most of the medical community ignores. There is a danger w/ Strum in that I think it is natural in this technology age to be overly impressed w/ complexity. The more technical jargon we hear, the more intelligent we think the speaker is. We are easily "baffled by bullshit" and associate that w/ insight. There is also an innate desire to identify w/ the rebel who bucks the big medico-pharma domination and global conspiracy to keep us sick so they can sell us more expensive drugs and treatments. Of course, cancer and microbiology are complex and, if a cure is found, it won't be by those who are content w/ the RP-SRT-HT-Chemo-RIP protocol. I.P., I must have missed that SVI study - can you point me to it? And thanks for that 3rd possibility, Leonard! Bill Denton RP 2/12/02 PSA .93 Memphis > Ed, I did not present any of that as fact - I simply stated it as > comments from a prominent oncologist who follows the traditional [quoted text clipped - 7 lines] > would like to send him a summary of your model - where can I find a > succinct statement of it? Bill, I understand that you were just presenting your oncologist's point of view. It particularly struck me that if you take the position that hormone sensitive PCa cells never mutate into AIPC, then logically, you must hold the belief that PCa always arises with two cells initially - one hormone sensitive and on hormone insensitive. I'm sure that this is not what that oncologist meant. I have created an Excel summary of my model, which can be downloaded from: http://www.math.uchicago.edu/~ed/preprint/Table1.xls If that gets his interest, then he should read my complete paper at: http://www.tbiomed.com/content/2/1/10 It is important that he read my paper and check my references before dismissing the model out of hand. The strength of my model lies in the solid research articles that I cited to prove each aspect of the model. Also, I would recommend that he read the article that I cited in my previous post to this thread. If he is not going to believe my model, then he should offer up a logical explanation of how ADT followed by T+F can ever produce results ~5 times better than continual ADT. Ed Friedman Ed wrote...snip... It particularly struck me that if you take the position that hormone sensitive PCa cells never mutate into AIPC, then logically, you must hold the belief that PCa always arises with two cells initially - Ed...I'm not sure that conclusion necessarily follows. For example, here are two alternatives that would not require the presence of both androgen-dependent (AD) and and androgen-independent (AI) cancerous cells when the PCa first arises: 1) sets of both AD and AI stem cells in the tumor 2) initially repressed genes that code for AI cells ...Ron > Ed wrote...snip... > It particularly struck me that if you take the position that hormone [quoted text clipped - 10 lines] > > ...Ron Ron, I think that you are talking semantics here. The point of a doctor saying that AD cells don't mutate into AI cells is to make it seem that there is no point in using ADT early. Whether the AD cells mutate, or have genes that become unrepressed, or eventually produce stem cells that create AI cells, the point is that it is absurd to say that PCa which currently only has AD cells will under no circumstances develop any AI cells if you let the tumor keep on growing. The fact is that most PCa starts with a single cancer cell that is AD, and eventually will produce AI cells as well. Ed Friedman Ed Friedman Ed wrote... Ron, I think that you are talking semantics here. The point of a doctor saying that AD cells don't mutate into AI cells is to make it seem that there is no point in using ADT early. Whether the AD cells mutate, or have genes that become unrepressed, or eventually produce stem cells that create AI cells, the point is that it is absurd to say that PCa which currently only has AD cells will under no circumstances develop any AI cells if you let the tumor keep on growing. The fact is that most PCa starts with a single cancer cell that is AD, and eventually will produce AI cells as well. Ed Friedman -------------------------------------------------------------------------------------------------------------------------- Ed...Perhaps this is semantics or perhaps I'm missing the point. When you initially wrote, "if you take the position that hormone sensitive PCa cells never mutate into AIPC, then logically, you must hold the belief that PCa always arises with two cells initially", I thought you were specifically referring to the androgen receptor mutation alternative. I thought you were saying that if you rule that mechanism out, then you need to have AI and AD cells at the outset. I was giving two alternatives that don't require both types of cells at the outset. Also, the cancer stem cells are there from the beginning, or so the theory goes...Ron > Ed wrote... > Ron, [quoted text clipped - 21 lines] > Also, the cancer stem cells are there from the beginning, or so the > theory goes...Ron Ron, I see your point, and your argument is probably stronger than mine. Part of the problem is that I believe that I know how PCa starts (unsuppression of a single repressed gene) and I believe that I know how AD becomes AI (any of a number of genetic mutations) and that knowledge colored my answer. Ed Friedman "It particularly struck me that if you take the position that hormone sensitive PCa cells never mutate into AIPC, then logically, you must hold the belief that PCa always arises with two cells initially - one hormone sensitive and on hormone insensitive. I'm sure that this is not what that oncologist meant." Ed, I don't know exactly what he meant but the implication is the same as if there were both types of cells ab initio: 1. At least by the time PCa is diagnosed there is a population of AIPC cells; 2. The natural growth of that population far exceeds whatever additional AIPC may arise from mutations, thus that is the popluation you have to worry about; 3. Therefore, early HT that only knocks out the ADPC population makes little difference in the long run. See Walsh's Guide at 353: "Scientists believe that these androgen-independent cells probably inhabit the prostate for years; they don't just suddenly appear one day after the cancer has been diagnosed." Thanks for the links; maybe we can educate this oncologist. :-) Bill Denton RP 2/12/02 PSA .93 Memphis > Ed, I don't know exactly what he meant but the implication is the same > as if there were both types of cells ab initio: [quoted text clipped - 18 lines] > PSA .93 > Memphis Bill, I agree that at time of diagnosis there are probably AIPC cells present. Please let me know what the oncologist thinks of my model. I'm especially interested in any data (either published or observed by him personally) that he feels is inconsistent with my model. So far, nobody has come up with any. Ed Friedman > I.P., I must have missed that SVI study [that showed a 30% "success rate" for SRT] - can you point me to it? I don't remember the source. My onc quoted it when I asked him about Strum's 7% figure. For my purposes, I'll wait until my PSA rises to research it. If you need it, I could ask my onc for the reference. I.P. |
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