Hormone therapy may boost prostate cancer growth
Comments
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A leap step taking us closer to the “Silver Bullet”
I believe in the main argument in this thread regarding the consequences in hormonal treatments/manipulations as an initiator in the so called refractory status. I have commented in my past threads about the danger involving continuous HT administration which may be behind the bandit’s wish in looking for survival at its own means. Oncologist researchers like Myers have studied the problem and by experience in treating his/their patients, they have confirmed that intermittent administration done with an appropriate protocol can extend the period of IADT for several years before refractory sets in. Refractory is a status given to the treatment when the bandit mutates its AR (androgen receptors) or when it starts manufacturing androgens for own survival.
In one of my threads of 2011, I had a similar discussion on the above with some of the comrades of this forum, in regards to the “behavioral adaptation” of cancer cells in surviving on low levels of testosterone. Cancer behavioral is triggered and reacts to survive by mutation. In this “adaptation process” the beneficial mutations are preserved because they aid survival. This is a process known as "natural selection" from Darwin’s theory. We all got it at all levels including the cancer. It is in our genes.
In my opinion, researchers of the above study (presented by SPT) reached further and found the genes involved in such survival principles. In any case, I think that linking HT treatment to the cause of “boosting cancer growth and making a tumor more aggressive” is over stating because we know that hormonal manipulations involve many weapons working solo (IADT) or in combination (IADT3) and aiming at several means of hormonal blockades. Another aspect to consider is the same principle in survivorship that can be expected to occur if cell’s DNA stability are threaten by bursts of radiation or chemo induced damage. Cells could be damaged and initiated to a status of cancer. That could be imagined as boosting cancer.
This finding in genes is now the subject for newer means of treatment of prostate cancer. We have been expecting this to happen and without doubts this will be the way for future interventions. It will be a more tailored way to treat each individual case that deals in fact with the cancer itself. Not as the present approaches that aim in dissecting/burning the whole flesh where the cancer is expected to hide. It makes me think that we are closer to the “Silver Bullet”.
Some of my inputs on the matter;
https://csn.cancer.org/comment/1013947#comment-1013947
https://csn.cancer.org/comment/1300510#comment-1300510
https://csn.cancer.org/node/241249
https://csn.cancer.org/node/267154
Thanks for starting this thread.
Best wishes,
VGama
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Back to the topic
Redbelly,
Just for the record, the effects of the hormonal blockades in the context of the radiation treatment are not well known. Researchers found it to improve survival rates (by approximately 30%) but have no definite conclusion on the reason behind the improvement. The combined therapy is recommended solo based on trial results done at many clinics around the world. It does not assure cure or avoid definite progression of the disease, but it extends life. The cost to pay are added risks and side effects.
One knows that the hormonal component does sensitize the cells to absorb better the ionizing radiation. This is what destroys the DNA killing a cell. Though, the best combination in hormonal blockade is not defined, however, the typical protocol involved in the trials was Lupron plus an antiandrogen (such as Casodex, Eulexin or Androcur). Zytiga is relatively new in the hormonal arsenal and may have not been present in the trials. This drug acts at the same time as an antagonist of cell's AR - androgen receptors (similar to Casodex) and agonist of ER- estrogen receptors. I wonder if it makes it a better weapon in the combi therapy.
Best,
VG
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thanks
thanks Vasco, I'm thinking and hoping it will be a better weapon. I thought I was ready for radiation, and tried on a couple of clamps this morning, due to incontinence. Neither seems to hold on to me. I guess the Lupron has shrunk me so much that I can't put one on....... Not sure what i'm going to do now
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Zytiga and Jevtana were both
Zytiga and Jevtana were both initially approved by the US FDA as drugs for "metastatic, castration-resistant, post-Taxane drugs." Both have been in clinical trials since for use earlier in treatment, some with dramatically improved results. I posted the results of a study on this some time ago, but have not found it again yet. I will continue to look.
I got interested in this in 2011 when my friend Gary was dying of PCa (he passed in 2013). I took him to most of his appointements, and met with his NP and doc. His oncologist was Clinical Trials Director for the teaching hospital Gary was using. But Gary himself was not in any clinical trials, and his use of the two drugs was in the only pattern then available: Taxotere, then them. Both probably gave him 6 months of life each. After RP failure 12 years before, he had received massive IMRT. This caused him horrible bleeding a few years later, which had to all be surgically cauterized in his colon and rectal area.
My only point is that Jevtana and Zytiga are indeed being tested in new ways, and it would be advisable to try to get into any of the trials that are underway. As commedians and song producers note, "timing is everything."
Jevtana is itself technically a "chemo" (a cytotoxic chemical), whereas Zytiga is technically a form of HT.
http://chemocare.com/chemotherapy/drug-info/Jevtana.aspx
http://chemocare.com/chemotherapy/drug-info/zytiga.aspx
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VGamaVascodaGama said:Separating the "wheat from the chaff"
Redbelly,
I do not recall your story and this forum's searching engines do not lead me to it. Is your incontinence a permanent issue or just a cause from the surgery of last May?
In my lay opinion (hope the administration doesn't delete this thread), if the case relates to the surgery and the improvement is not set yet then you should try postponing the RT (radiation) while continuing HT to pin down the bandit. The RT portion in the combi treatment will later take its stand in the fight with no prejudice to the overall outcome. Discuss the matter with your doctor.
I think your case being classified low or intermediate risk at the initial diagnosis, thought it be a contained case for the choice on surgery, but your treatment could belong to those aiming in attacking the bandit from all fronts (the mother of all treatments as I call it). However, only highly risky cases are doomed to the need of earlier attacks. Emergency does not make part in prostate cancer affairs but doctors prefer to keep the protocols of certain treatments which could be your situation.
I wonder if the choice was for a combination therapy starting with neoadjuvant RP (surgery) to be followed with adjuvant RT + HT. This sort of protocols usually require earlier radiation to assure better outcomes (you can read about the excellent outcome of above Will Doran's story). On the other end, if your RT is suggested as a salvage treatment then you can do it latter once the incontinence issue has improved. This is what I would do if in your shoes.
To add to the above and with regards to Max's comments, I question the reason for the inclusion of Zytiga. As Max says this drug is typically recommended in advanced metastatic cases that are moved to powerful attacks. Surely it should work in low risk treatments but surely it is also connected to an increased number of side effects over the more traditional HT drugs.
Within the HT weaponry, Zytiga has three functions acting at the same time; it acts as an antiandrogen, it acts as a 5-ARI (five alpha reductase inhibitor) and it promotes the increase of estrogens to replace the testosterone in needed systems. Together with Lupron (LHRH agonist) it covers the total blockade typically called ADT3 or MAB by physicians. 5-ARI drugs aim to avoid the metabolism of testosterone into dihydrotestosterone, a tenfold refined and powerful androgen most wanted by the bandit. The increase of estrogens in circulation will make us fatter but it will help in the good functionality of several systems/organs dependent on the testosterone.
A note to SPT above;
We have previously discussed here on the differences between endogenous and exogenous testosterone. PCa seems not to recognize exogenous stuff (TRT) so that its influence in prostate cancer treatment seems minimal. In fact this controversy started more than 20 years ago by the time Dr. "Bob" Leibowitz (a famous PCa oncologist) started using TRT in prostate cancer patients (http://www.compassionateoncology.org/). The controversy was increased when Dr. Abraham Morgentaler (an expert on sexuallity issues) alerted for the risks of low levels of endogenous testosterone in men. He applauded TRT and related its influences in prostate cancer development. Unfortunately I cannot find my own posts on the issue but you may be interested in this link;
https://csn.cancer.org/node/212885
Regarding the radiation absorbed by tissues, you may know that these differ depending on the grade of the delivered energy when in traditional tests or in RT therapies. CT uses X-ray type so that its influence is minimal but the contrast agents injected in the patient are very armful for the kidneys. PET and other gamma machines deliver higher energy more armful in certain tissues, which tests should only be done when necessary, not as a frequent typical test. RT therapies use higher concentrated energy to destroy the DNA strands and that can cause irreparable damages where delivered (at the field of attack).
https://www.quora.com/Whats-difference-between-PET-scan-CT-scan-X-Ray-and-MRI
RT, therefore, should be a choice when it assures high probabilities of success. Defined targets should exist in advance of an attack and that is why proper image studies become indispensable in the diagnosis. I think you say it correctly, to avoid scans that one knows to be unfeasible for the purposes. MRI is without doubts the safest and best to be used when uncertainty exists but it cannot separate the "wheat from the chaff". It cannot distinguish malignant cancer from benign tissues. PET on the other hand with a due isotope (like PSMA in PCa cases) manages to provide results highly appropriate in a diagnosis done to define a therapy.
My case follows that principle as an example. I could have done a PET scan already but I have been waiting in the past five years for higher level of PSA (close to 2.0 ng/ml) before engaging in a PET F18-fluorocholine so that it assures me a more reliable result. A PET Ga68-PSMA could be done much earlier at a PSA level of >0.70 ng/ml but it was not at my reach.Best,
Vgama
Vgama
Thanks for the response. I agree with everything you wrote except this one point:
"MRI is without doubts the safest and best to be used when uncertainty exists but it cannot separate the "wheat from the chaff". It cannot distinguish malignant cancer from benign tissues. PET on the other hand with a due isotope (like PSMA in PCa cases) manages to provide results highly appropriate in a diagnosis done to define a therapy."
For bone metastatses MRI can distinguish cancer from benign tissues. It's quite a bit better than PET, which is subject to false positives because the isotopes go wherever bone is growing. MRI detects the morphological changes in the bone associated with mets.
"Whole-body MRI is more sensitive than scintigraphy in the detection of bone metastases. This is partly due to the lower spatial resolution of scintigraphic images but also reflects that scintigraphy detects bone remodeling, whereas MRI detects structural alterations in bone marrow. Several small studies have reported sensitivities and specificities of the different imaging techniques. Reports of sensitivity of whole body MRI range from 97.5-100%, compared to 26-71% for 99mTc scintigraphy. Although CT has a high sensitivity for soft-tissue metastases, the sensitivity for the detection of bone metastases has been reported to be 10%." Massachusttes General Hospital Radiology Rounds, Whole-Body MRI
In the quote, "scintigraphy" is PET. That article was written in 2010, like all else there has been a lot of progress in 7 years. Whole-body MRI is much better and more widely available. I get whole-body MRIs annually to check for distant metastases.
Localized MRI is pretty good at detecting malignancies. My multi-parametric prostate MRI had no trouble detecting the tumor and enlarged lymph nodes, and these days they can even tell high-grade tumors from lower grade. It's not as deterministic as a Gleason score from a biopsy, but you can get a pretty good idea without a biopsy and without exposure to ionizing radiation.
If, and only if, my medical team convinced me that the results of an MRI strongly suggested using CT or even PET/CT to investigate further, I might consent. But I would always insist on the MRI first, and then I would ask hard questions about what would be learned in an additional test that would change my treatment.
If they can't answer that question, don't take the test. That last part is not my advice, but of urologist Dr. Cooperberg.
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Vasco
My info is age 54, biopsy in Feb, Gleason 9, Thought contained, RALP on May 30th. Was in margins and seminal vesicles and micros in bed, I guess. They are planning on radiating the bed, next to the bladder. I think they classify me as high risk. But my PSA's are .01 at Emory and .04 in Albany. Anyhow, I'm battling the tiger best I can. As far as weight gain, I've actually lost 6 lbs from the last visit and been on Zytiga 6 weeks.
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Adverse post-surgery pathology patient
Redbelly,
Your reply tells me that your case groups with what we call “Adverse post-surgery Pathology” patients. These are cases with advanced stages of T3/T4, high Gleason score and positive margins. The PSA seems low if we judge it against the findings but it could be that your type of cancer produces less amounts of the stuff (typical in aggressive type of cancers). I do understand now the reason for Zytiga. Even without RT you cannot avoid this fast start of HT involving as many blockades as possible. Many guys with similar pathological stage (that also includes spread of seminal vesicles) are moved into combination therapies of Chemo plus hormonal (recall Max comments above), before attacking with radiation. I would think that the image studies done at your initial diagnosis were negative and probably the biopsy did not detect PIN or cancer closer to the shell, leading to judge it as contained.
Your doctor wants now to try cure with salvage radiation. The hormonal component will render the PSA improper for any judgment. The radiologist will define the field of attack comparing past images with the ones he will do when defining the isodoseplan. Most probably he will radiate the typical areas targeted in SRT approaches that include localized lymph nodes, the bed and tissues surrounding the bladder. I would recommend you to meet the radiologist and express your worries regarding the incontinence issue. SRT can also cause stool incontinence and it is prohibitive if you have/had any ulcerative colitis case (get a colonoscopy in advance). He can always avoid some spots or attack them with lesser doses.
Unfortunately, newer genetic tests are still immature to predict the best or worse type of salvage therapy for a case like yours. There have been incredible advancements in the genetic researches and they have found already a gene in PCa indicating if the bandit would disregard any radiation attack. In fact it is known that cancer with such a gene may develop further if radiation or chemo is administered. In any case, you could do and rely on a genetic test to verify the benefit of certain drugs in your future attacks, if any.
Best wishes and luck in your newer treatment.
VG
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Separating the "wheat from the chaff"
Redbelly,
I do not recall your story and this forum's searching engines do not lead me to it. Is your incontinence a permanent issue or just a cause from the surgery of last May?
In my lay opinion (hope the administration doesn't delete this thread), if the case relates to the surgery and the improvement is not set yet then you should try postponing the RT (radiation) while continuing HT to pin down the bandit. The RT portion in the combi treatment will later take its stand in the fight with no prejudice to the overall outcome. Discuss the matter with your doctor.
I think your case being classified low or intermediate risk at the initial diagnosis, thought it be a contained case for the choice on surgery, but your treatment could belong to those aiming in attacking the bandit from all fronts (the mother of all treatments as I call it). However, only highly risky cases are doomed to the need of earlier attacks. Emergency does not make part in prostate cancer affairs but doctors prefer to keep the protocols of certain treatments which could be your situation.
I wonder if the choice was for a combination therapy starting with neoadjuvant RP (surgery) to be followed with adjuvant RT + HT. This sort of protocols usually require earlier radiation to assure better outcomes (you can read about the excellent outcome of above Will Doran's story). On the other end, if your RT is suggested as a salvage treatment then you can do it latter once the incontinence issue has improved. This is what I would do if in your shoes.
To add to the above and with regards to Max's comments, I question the reason for the inclusion of Zytiga. As Max says this drug is typically recommended in advanced metastatic cases that are moved to powerful attacks. Surely it should work in low risk treatments but surely it is also connected to an increased number of side effects over the more traditional HT drugs.
Within the HT weaponry, Zytiga has three functions acting at the same time; it acts as an antiandrogen, it acts as a 5-ARI (five alpha reductase inhibitor) and it promotes the increase of estrogens to replace the testosterone in needed systems. Together with Lupron (LHRH agonist) it covers the total blockade typically called ADT3 or MAB by physicians. 5-ARI drugs aim to avoid the metabolism of testosterone into dihydrotestosterone, a tenfold refined and powerful androgen most wanted by the bandit. The increase of estrogens in circulation will make us fatter but it will help in the good functionality of several systems/organs dependent on the testosterone.
A note to SPT above;
We have previously discussed here on the differences between endogenous and exogenous testosterone. PCa seems not to recognize exogenous stuff (TRT) so that its influence in prostate cancer treatment seems minimal. In fact this controversy started more than 20 years ago by the time Dr. "Bob" Leibowitz (a famous PCa oncologist) started using TRT in prostate cancer patients (http://www.compassionateoncology.org/). The controversy was increased when Dr. Abraham Morgentaler (an expert on sexuallity issues) alerted for the risks of low levels of endogenous testosterone in men. He applauded TRT and related its influences in prostate cancer development. Unfortunately I cannot find my own posts on the issue but you may be interested in this link;
https://csn.cancer.org/node/212885
Regarding the radiation absorbed by tissues, you may know that these differ depending on the grade of the delivered energy when in traditional tests or in RT therapies. CT uses X-ray type so that its influence is minimal but the contrast agents injected in the patient are very armful for the kidneys. PET and other gamma machines deliver higher energy more armful in certain tissues, which tests should only be done when necessary, not as a frequent typical test. RT therapies use higher concentrated energy to destroy the DNA strands and that can cause irreparable damages where delivered (at the field of attack).
https://www.quora.com/Whats-difference-between-PET-scan-CT-scan-X-Ray-and-MRI
RT, therefore, should be a choice when it assures high probabilities of success. Defined targets should exist in advance of an attack and that is why proper image studies become indispensable in the diagnosis. I think you say it correctly, to avoid scans that one knows to be unfeasible for the purposes. MRI is without doubts the safest and best to be used when uncertainty exists but it cannot separate the "wheat from the chaff". It cannot distinguish malignant cancer from benign tissues. PET on the other hand with a due isotope (like PSMA in PCa cases) manages to provide results highly appropriate in a diagnosis done to define a therapy.
My case follows that principle as an example. I could have done a PET scan already but I have been waiting in the past five years for higher level of PSA (close to 2.0 ng/ml) before engaging in a PET F18-fluorocholine so that it assures me a more reliable result. A PET Ga68-PSMA could be done much earlier at a PSA level of >0.70 ng/ml but it was not at my reach.Best,
Vgama
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My issue is not with the
"I respect their choices, but I fear that most of those choices are made because doctors lie and conceal the truth about their "treatments."
The alternative medicines nearly always make you feel better, improve your health, and many of them can be used with conventional treatment to make it work better and reduce some of the worst effects. It is your life and your choice."
My issue is not with the science (or not) with the referenced document. It is with OPs agenda. This post was preceded with a post that was openly and unfoundedly hostile and critical of hard peer reviewed and clinically evidenced science (that saved my life and has saved the lives of hundreds of millions of people) and promoting what Prof. Brian Cox calls (rightly so) "woo woo". At the same time, OP suggests that science should welcome dissent. It does, through the medium of debate, research and peer review all based on evidence and fact. I repeat my statement in that thread - if an alternative medicine works it becomes mainstream, period. Herbal medicine preceded modern medicine, was suppressed (witchcraft etc.) and has again become mainstream and monetized as big pharma begins to exploit the rainforest. Meditation is proven of benefit for mental and physical wellbeing. Surgery has been performed under acupuncture and hypnosis. I have seen and experienced interesting phenonena doing martial arts and tai chi. On the other hand, Steve Jobs and many others (often celebrities) died by rejecting conventional medicine and choosing unproven I'm not even sure what to call them as the word is not treatments.
At the same time, Vasco (who is being far more of a gentleman that me in this thread) gets penalised for giving well researched and scientifically founded advice.
I don't care what people believe and I won't try and shut them up down the pub or on the street corner but I damn well will take a stand in a forum like this where desparate people will grab at anything for a chance of life. I've lost (and currently losing) too many people to cancer to sit idly by.
C
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MRI is friendly but not good in detecting small sized tumors
SPT,
I do not know if you are correct in regards to the higher capability of MRI detecting PCa bone metastases against PET but I disagree that MRI is better in detecting PCa when this refers to a small sized tumor. CT and MRI cannot detect small tumors that lay within their planes. In fact, all scanning machines/equipments have limitations in their detection capability. If one refers to the average; CT requires sizes over 1.2 cm, MRI over 0.7 cm and PET over 0.3 cm, to assure a reliable result. The image produced by the computer stretches the lines make it unreal to the view. When using the PSA as a reference for reliability, the average stands in; BS (PSA>20), CT (PSA>10), MRI (PSA>2) and PET (PSA>0.5).
The dye used in MRI machines is friendly but limited to deformation which may not be useful without a previous image used for comparison. Experienced radiologists manage to get excellent results out of a primer scan (first MRI test) when fusing various data from other tests that could originate from ultrasounds, Doppler and CT (commonly referred as mpMRI). Unfortunately to us patients, the best results are obtained using radioactive-tracers armful to the body that together with an isotope specific to the type of cancer, such as the Prostatic Specific Membrane Antigen, manages to identify and locate those tiny cells involved with such a protein. The choice of the isotope is important and probably a choline based will not be so reliable in bone metastases. One must gamble in the judgment.
I disagree with the quote that "Scintigraphy is PET”. PET uses gamma rays capabilities (similar to scintigraphy scans like the traditional Technetium-99m BS scans) to identify/locate the various radiotracers but the cancer will be detected where the attached protein is found. Technetium-99m is not used as the transporter/carrier of such protein in PCa PET exams. Surely these also fail as it accumulates more at certain areas in the body. For instance, in the typical Ga 68–PSMA PET one finds an higher accumulation in the kidneys and mouth which by experience is taken as a false positive due to the low probability of existing PCa in those places. This is in fact one of the limitations in PET exams making it still not 100% reliable, but close to a better result.
Another aspect to take into consideration is that Full Body MRI machines are rare and not available everywhere. You are fortunate for having that machine close to you.
Best,
VG
0
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