We know that ADT can kill hormone-sensitive prostate cancer cells. What happens to healthy prostate cell when Testosterone goes below castration level? Do they still produce PSA? How they are impacted by lack of Testosterone?
I have done a great deal of searching without getting a satisfactory answer. If anyone knows about some sources answering my questions, please share with me.
It’s my understanding that ADT does not kill prostate cancer cells, just slows them down...
Some ADT drugs lower testosterone, others work on the receptors of the cancer cells and prevents them from receiving the testosterone,
As to what occurs to the healthy cells, denied testosterone is what the side effects are about , tired, hot flashes, etc.
This was discovered by Huggins & Hodges in 1941. Healthy prostate cells won't multiply without androgens. The prostate without androgens will shrink and atrophy from disuse ("involution"), but it does survive. Prostate cancer cells that still require external androgens to grow are different - they will die if they can't grow. If you think of DHT as a powerful androgen, you can see what the effect of blocking it is on healthy prostate tissue - Proscar shrinks BPH but leaves healthy cells intact.
Thanks this is the answer I have been looking for. Does this imply that after being on ADT for a while we shouldn't expect much of the PSA coming from the healthy prostate cells?
Yes. Only unhealthy prostate cells (prostate cancer, prostatitis, BPH,or mechanically disturbed) put out PSA into the blood serum.
So you're stating that healthy prostate tissue does not produce psa? If that be the case, where does the psa that men without cancer produce come from?
A man with a healthy prostate is not likely to be on ADT.
Healthy prostate tissue certainly expresses a lot of PSA. However, expressing PSA and detecting it in the serum are two different things. A 20 year old man has a serum PSA that is undetectable. As we age, the prostate glands that produce semen, etc. are less perfectly formed, and the cells are increasingly hyperplasia. These disruptions of healthy cells dump their PSA into the serum.
I think he means healthy prostate cells don’t produce PSA if you are on ADT.
" For all the uncertainties about the PSA, at least we can be sure the name is accurate.
Wrong. The protein that bears the name "prostate-specific" has also been detected in other organs, including the liver, pancreas, salivary gland, and breast (even in females). Only tiny amounts of PSA are present in these tissues. Still, purists might prefer the name Prostate Almost-Specific Antigen, while wags might suggest Perplexing Semantic Anomaly."
health.harvard.edu/newslett...
And apparently not all prostate cells make PSA
Only the PSA released into the blood stream is detected by blood test. A healthy prostate cell can produce plenty of PSA, only a small fraction of which might be released into the blood stream.
Hi, just for some more understanding -
1. If ADT also kills the prostate cancer cells, why is only chemo called cyto-toxic ? I have read several places which mention ADT does not kill the PCA, just slows its growth, Chemo actually kills the PCA.
2. ADT stops the food of prostate cancer cells, testosterone, eventually leading to their death - does it mean the healthy cells which survive mutate into different forms say neuroendocrine or small cell ? or do the fittest cancer cells survive in-spite of ADT and grow and mutate to these different forms ?
1. chemo kills many cells, thus "cytotoxic."
2. No, it does not mean that healthy cells mutate without testosterone. Neuroendocrine and small cell are rare kinds of prostate cancer.
Hi Tall Allen
You mentioned Proscar (5mg). Am I correct to understand this is finisteride and Propecia (1 mg) is also finisteride.
But these are delivered at the different dosages I showed above.
I understand Propecia is usually prescribed for hair loss.
Proscar for shrinking prostate, or also possibly prescribed for splitting into 1/4 pills for hair loss as this is a way to obtain the drug at much lower cost.
So say I had a PSA of 3.5 (picked that to be under 4). Still have my prostate (not sure that matters).
Then I go on Proscar, how will my PSA value change. Will that new value mask my true PSA, or will my new PSA be the accurate representation of my PSA.
Does taking 1/4 pill of Proscar daily affect PSA the same as a full pill daily?
Same question for propecia, what would my PSA score be? The same as if I took the Proscar pill?
Will the expected drop in PSA be the same if I just started either drug or I am on Proscar or Propecia for many years.
Now assume you've had RP or radiation to the prostate.
Does continuing on any form of finisteride make any sense or have any effect on PSA, prostate, or hair loss after RP or radiation to the prostate.
Hope that wasn't too many questions.
Finasteride will have no effect on serum PSA if you've had an RP or radiation. It only shrinks BPH.
Thanks tall_Allen
Do you have a answer how PSA is reduced/ masked by Propecia and also by Proscar, is there any difference in reduction between the two different dosages?
Let me try to explain again. Finasteride only lowers the PSA due to BPH. Lower doses have less effect on BPH.
hopkinsmedicine.org/brady-u...
Tall_Allen I am always impressed by your knowledge of seemingly all things prostate related. You are truly to be admired for your extensive knowledge and the help you provide to all of us "Brothers" and their family members.
I think some of us have seen an article like the above link to the the article titled Finasteride: Are the Risks Worth it? - Johns Hopkins Medicine
I've copied it in whole below
In the section labeled "Risky Business for Two Patients" it speaks specifically about two patients taking Propecia for hair loss and talks about the effect on their PSA. There is a chart as well showing the formula for calculating PSA based on how long you are on finasteride.
Can you provide alternate documents or articles that show this article is incorrect?
Thanks Again for your help.
Finasteride: Are the Risks Worth it?
Updated: 12/21/2015
Does finasteride prevent prostate cancer? According to Patrick C. Walsh, M.D., University Distinguished Service Professor of Urology at Johns Hopkins Medicine, it just prevents you from knowing that you have it. Even worse, taking finasteride may mask the signs of aggressive, yet curable prostate cancer until much later.
Many of Dr. Walsh’s patients have asked him about an article that appeared in The New York Times on Sunday, June 15, 2008. It claimed that finasteride somehow helps men by preventing them from knowing they have prostate cancer so they can avoid the potential side effects of treatment.
Finasteride hides higher-grade cancer
The trouble with finasteride dates back to 2003 when the original article was published in the New England Journal of Medicine. The authors of that article studied 18,000 men who randomly were assigned to receive either 5 mg of finasteride (then used mainly to treat benign enlargement of the prostate) or a placebo.
The men in the finasteride group had a 25 percent lower risk of being diagnosed with prostate cancer, but a 68 percent higher risk of being diagnosed with a high-grade disease defined by a Gleason score of 7 to 10. (This high-grade type of cancer is usually more difficult to cure.) Since then, the authors of the article have tried to erase these results and encourage urologists to prescribe finasteride for prostate cancer prevention. When these attempts failed, they started approaching patients and physicians directly.
No Decrease in Positive Biopsies
During the first seven years of the study, the patients had a biopsy if they had an abnormal finding on a digital rectal exam or if their PSA became elevated. But because this was a double-blind study, the patients taking finasteride did not know that their PSA levels were artificially low.
Therefore, fewer patients taking the drug who were told to have a biopsy followed that advice. Were there fewer cancers in these patients because finasteride actually prevents cancer or because fewer men got a biopsy in the first place? Did their low PSA levels fool them into thinking they couldn’t possibly have cancer? In this study, 15 percent fewer men on finasteride underwent a biopsy because they were lulled into a false sense of security by their low PSA level.
Thus, the major effect of this drug was to keep patients from knowing that they even needed a biopsy. Of the men in the study who actually had a biopsy, the frequency of positive biopsies for cancer was statistically the same in patients in both test groups.
Dr. Walsh is very concerned about the increase in high-grade disease and the possibility that this presents an unacceptable risk for a form of treatment that has little or no value.
Among finasteride’s critics is Stewart Justman, who wrote a book called Do No Harm: How a Magic Bullet for Prostate Cancer Became a Medical Quandary. In his review of the publication for the New England Journal of Medicine, Dr. Walsh noted that when patients on finasteride are diagnosed with prostate cancer, they are more likely to have dangerous, high-grade disease.
The real danger is that many patients will be lulled into a false sense of security. If you are told that you’re on a drug that will prevent cancer, and your PSA falls, you aren’t going to be on your guard.
Risky Business for Two Patients
Dr. Walsh has seen this risk in action in multiple patients. Two cases involved men who had been taking Propecia, a form of finasteride that’s used to restore hair loss, for 10 years. One man had a PSA of 3.8 ng/ml, and the other had a PSA of 4 ng/ml. Since finasteride lowers PSA levels, some calculations are needed to determine the true PSA number for each patient. These men actually had PSA levels between 9 ng/ml and 10 ng/ml. Both of them had high-grade prostate cancer classified as Gleason 8 disease that had spread outside the prostate. One of them had a positive surgical margin. If surgical margins (the edges of the removed tumor) are positive, they show cancer cells or indicate that the cancer is just a short distance from the edge of the specimen.
Avoid finasteride to save money and reduce risk of high-grade disease
Dr. Walsh has been greatly troubled by the pressure for patients and general physicians to use finasteride. His conclusions about this drug include:
It has no primary effect in reducing the number of men who will have a positive biopsy.
Patients will believe that it prevents cancer, will be pleased that their PSA levels fall and will not understand the potential danger of developing undiagnosed, high-grade disease.
Finasteride can be used as a treatment for an enlarged prostate, as long as patients who are being screened for prostate cancer understand the guidelines. If you don’t want to know if you have prostate cancer, you should just avoid PSA testing.
According to Dr. Walsh, if you want to prevent prostate cancer, finasteride is the last thing you should take. Save yourself the yearly cost of the medication and avoid the increased risk of high-grade disease. The only thing that finasteride can do is prevent you from knowing that you may have lethal cancer until it may be too late to cure.
How to Determine Your Real PSA Level
If you are taking finasteride, you need to be able to determine your actual PSA level.
If you have been taking the drug for:
Two years: Multiply your PSA by 2
Between two and seven years: Multiply your PSA by 2.3
More than seven years: Multiply your PSA by 2.5
If your PSA begins to rise, get a biopsy immediately.
I have no idea what you are inferring. Why would I say the article is incorrect (although it has since been disproven that the risk of high grade disease is increased.)? Finasteride only cuts the PSA from BPH (as I keep telling you).
Tall_Allen
I'm sorry this question and response has taken the turn it has. You usually back up your statements with links to documented proof.
I expected you could produce written pier reviewed science documents or articles disproving this article from John Hopkins, and backing your alternate assertions.
Looks like I will need to contact John Hopkins for their response.
At any rate I thank you for your effort.
I have no idea what it is you would like to see proof of. You are not being clear at all. Quoting all of their old article doesn't help. What is it exactly that you think is (or was) controversial? As I said I do not object to most of what JH said in that outdated article. Do you mean about the high risk overdetection? Here's a more recent understanding:
nejm.org/doi/10.1056/NEJMc1...
As you see, it was only detection and ascertainment bias, not a real effect.
Finasteride actually increases the effectiveness of PSA in detecting prostate cancer. Because it eliminated the PSA due to BPH (which cuts PSA in half), what is left is mostly the PSA due to prostate cancer. So if finasteride just cuts PSA in half (approximately) and it stays at that level - there is no need for a biopsy. But if finasteride doesn't cut PSA at all, or if it cuts PSA and then it rises while on it, that is reason for a biopsy.
Please be specific about what it is that you do not understand. I'm not a mind reader.
Not sure about dosage here, but I have heard that men (with prostates) taking Proscar may eventually see PSA readings of only about half of what they would otherwise be. I do believe that can happen at the smaller doses, too.
So a guy taking it might have a PSA of 4, but if he wasn't taking it then it would've been 8, possibly triggering a call for biopsy.
Not sure if TA is right about zero effect after RP. I recall hearing it can either delay PSA progression or mask it, and my understanding is that you might still want to double the PSA number to get the "real" level. Some MO docs have used "proscar maintenance" as part of continuing treatment after a course of ADT. Worth researching!
In rat studies, castration leads to a dramatic reduction in the size of the prostate. (With restoration of testosterone [T], the prostate grows back to adult size. Stem cells do not require T & therefore survive.)
In studies of eunuchs, the prostate seems to generally shrink to prepubertal size (about 4 grams), but in older eunuchs, the prostate may even be inpalpable.
The thing to remember, I think, is that a healthy adult will maintain prostate size - cell death & cell division are balanced. After castration, cell deaths will continue to occur, but cell division of normal cells will not.
Does the absence of T contribute to cell death? Perhaps, IMO.
-Patrick
T:
All prostate cells output some psa. That is why the standard for us older guys is set at 4. The difference is that prostate cells exhibit higher levels, which is why not only the score but the rise in score are signs of pc.
Also, this is assuming one still has a prostate, most of us have it removed or blasted to never never land, so will have very low psa readings. There is some issue with some prostate gland cells remaining which will also exhibit psa so in an-exact science. That said, it is still the standard used to disagnose and treat pc.
I noted that Dr. G. Murphy was the co-inventer of the psa test, and just prior to his passing, noted that he never expected that it would still be in use at the time, never mind some 20 years after he died. He was a great man and scientist and was a 10 on scale ten, a true warrior who sacrificed much to help us men.
Here is a list of my PSA & Testosterone level:
*Hormonotherapy pour 168 days (2020/04/04). Dose (Eligard 45 mg) incomplete. Casodex 50mgX30 jours.
(2020/05/31) + (2020/08/24)Lupron Depot 22.5mg/ 12 semaines X 2
*Testosterone 15.40 nmol/L - 444ng/dL (3.0 à 27.4nmol/L 86.526 à 790.2708ng/dL)(1nmo/L=28.842ng/dL)
Level below castration = 0.7nmol/L - 20.189ng/dL
10.30nmol/L - 294.19ng/dL (2020/05/04), 15.2nmol/L - 438.04ng/dL (2020/05/27), <0.2nmol/l - <5.768ng/dl(2020/07/29)
* PSA μg/L = 4.23 (2001/07/18), 2.2 (2002/07/23), 1.8 (2006/07/04), 2.2 (2008/09/22), 2.4 (2009/05/20), 2.05 (2011/08/26), 2.25 (2012/08/13), 2.05 (2013/08/06), 2.77 (2014/07/28), 3.84 (2015/07/06), 1.97 (2016/06/30), 3.89 (2017/06/13), 6.8 (2019/09/10), 11.7 (2019/10/28), 13.7 (2020/01/08), 16.7 (2020/03/02), 20.4 (2020/04/06),
Per-Hormonotherapy = 1.76 (2020/05/04), 8.58(2020/05/27), 0.18(2020/07/29)
My 1st PSA test, I was 54 y.o. And as you can see, my PSA play yo-yo.
My first two T test were post Eligar incomplete.
PSA is mainly produced by the prostate but low levels are produced elsewhere.
Men who have had bladder cancer and have had the bladder, prostate and all the associated gubbins cut away may still exhibit very low levels of PSA as do some adult women, ca 0.1.
In the absence of testosterone, prostate cells divide very slowly and the rate of cell death exceeds the rate of cell creation by a large margin. I suspect that small groups of prostate cancer cells may not survive a prolonged period of ADT but larger groups do.
With the prostrate potentially shrinking so dramatically it sounds like it could impede urine flow through the urethra. I was hoping that ADT would help with my urinary issues. I am experiencing extreme pain, so I conducted a urinalysis, CT for kidney stones and am currently on Urogesic Blue. All to no avail. I remember speaking with Dr. Scholz about this a while ago and he indicated that it's possible. My radiation Oncologist told me not to do anything surgical or mechanical to help with my flow due to having HDR and IMRT as my initial treatments. What if anything are my other options?
My understanding is that prostate cancer cells, like all cancer cells, do not know how to die as normal cells do. And ADT slows their growth by reducing testosterone.
Also it seems to me that often some prostate cancer cells remain in the body after surgery or radiation therapy, and those live on to grow, (becoming advanced or metastatic), often in lymph glands which act like filters which then trap the larger cancer masses which grow into tumors which can then spread elsewhere like to nearby bones and organs.
So to answer your question, in my humble opinion, healthy prostate cells are slowed in growth by the ADT (by lowering of teststerone), but not killed. and if and when the testosterone levels return to normal, they grow and die as normal. ADT can lower testosterone significantly but not to zero, thereby allowing both healthy and cancerous prostate cells to live on with reduced growth. With prolonged ADT the normal healthy prostate cells eventually die out faster than they can grow, and therefore are gradually eliminated. The cancer cells stop or slow growth, but do not die, and thus must be killed or eliminated by other means.
not important, keeping test as low as possible is best but also the lower the more side effects, so a catch 22, take injections, cancer feeds off of test so best to live large and do as much as you can in terms of quality of life!!!
Is there a connection between testosterone level and severity of prostate cancer at diagnosis?
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