I asked my MO early on if ADT kills PC cells or do they simply go dormant?
He stated that they go dormant. Since this discussion I have read that ADT starves cancer cells of T and then they die off.
So do they die or simply go dormant, or is it a mix of both?
Some die some don't die. There is a selective pressure I belive. Some strains survive and they could take over, repopulate the space. And if nothing else than the cancer stem cells survive.
Again, it is my personal interpretation and I am not a doctor.
For sure it is (ADT) a most effective way to survive as long as possible if you have a PC.
Why are you asking this question?
Thanks! Asking the question since my MO said they go dormant and did not add in that some are killed. I want to understand this disease.
The way I understand it is it helps the radiation kill them. They are weakened, and radiation changes their ability to grow.
It kills many. Some may survive.
My recent SPECT scan (CAT+radioactive dye) was interpreted as "some masses or lesions had shrunk significantly from a year ago and first diagnosis. And some were quiescent." So evidence of cell death. And great news. But as Tall Allen says - they don't all die and there is evolutionary selection pressure with the stronger surviving cells then taking over. There's a lot of research on thus phenomenon as a possible key to preventing the still inevitable evolution to "castrate resistance".
At the risk of using Dr. Google, here is what ADT does to cancer cells...
health.harvard.edu/blog/hor...
Excerpt
"April 27, 2015
By Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases
By Charlie Schmidt
When prostate cancer spreads from the prostate gland into nearby lymph nodes or bladder tissue, it is called locally advanced prostate cancer. The standard treatment for it is a combination of radiation therapy and hormone therapy. Radiation kills prostate cancer cells. Hormone therapy, formally known as androgen deprivation therapy (ADT), deprives prostate cancer cells of testosterone, which they need in order to grow and spread."
So ADT may or may not result in some PCa cell lines going away, but it should buy time to next available treatment should it fail.
In the 1990s, there was the belief that Lupron (ADT), via neoadjuvant delivery, in other words before prostatectomy, could cure prostate cancer. To pursue this theory, pathology departments involved did what is called whole mount sectioning of the prostate. Whole mount sectioning was a much more resource-intensive extensive sampling of the prostate to try to prove a negative (No evidence of Disease). A significant number of patients had no evidence of disease (NED) in their prostatectomy specimens after neoadjuvant Lupron and appeared to be possible cures. Needless to say, many of the patients were cured, but not significantly more than those who did not get neoadjuvant therapy. Also, those that had NED did better than those who did not.
Those that had no evidence of disease, after exhaustive examination of the prostatectomy specimen, and were not cured, obviously had microscopic residual disease outside the prostate that was not killed by Lupron.
Whether you call the residual microscopic disease dormant or active may be a semantic argument. ----- By the usual definition of dormant (not dividing) vs. active(dividing) in a malignant neoplasm, one would have to prove that the microscopic disease is either mitotically inactive (dormant) or mitotically active. How would one do that? But certainly, by the time the neoplasm is detectable as a recurrence and can be biopsied to do this test, the cancer must be mitotically active (have dividing cells) and thus is not dormant. Otherwise, how else did the cancer grow to a size to be detectable? Furthermore, I have never seen a cancer that does not have dividing cells, as measured by Ki67, a marker of cells which have entered into the cell cycle of division. So, me personally, I do not believe in dormancy, except for the semantic argument of defining dormancy as having a very long doubling time, such as > 15 months. However, I do believe that many patients have such a low tumor burden/microscopic disease which in combination with a long doubling time may take years maybe even more than a decade to become large enough to be clinically detectable; less so now, FDA approval 2020-2021, as we have entered the realm of PSMA-PET advanced/disruptive imaging which can detect disease orders of magnitude smaller than conventional imaging: CT and bone scan (PSA 4-10 vs. PSA of 0.2).
ADT kills prostate cancer cells, probably to a degree reflected by post-treatment PSA nadir. For example, if one has a PSA nadir that is a 99.9% decline from pretreatment, this suggests a death of 99.9%. And in fact, the depth of post-treatment PSA nadir is a significant prognostic factor in mHSPC.
I applaud Gym-rat for wanting to understand prostate cancer.
Allmo - since I just went through a trial on this, let me provide an update. Indeed, the1990s trials of neoadjuvant adt prior to prostatectomy did not conclude this was effective, as you say. But one of the reasons is that adt alone doesn’t fully block T. There is always a bit made in the glands that can keep some cancer cells alive but dormant. There are now ongoing trials with stronger neoadjuvant T blockers before surgery. In my case, I was in an NIH trial with 6 months of “intensive” ADT (goserelin, enzalutimide, abiraterone, prednisone) followed by surgery. I started with Gleason 9 (5+4). After surgery there was no evidence of any cancer in my removed prostate. Now, 3 years later, psa remains undetectable. Certainly this “intensive” ADT killed cancer cells. Did it kill all of them? Time will tell but so far so good.
Thank you Tony. I had no idea researchers are still pursuing this. Please keep me posted. And bravo to you for volunteering to be a guinea pig to push forward our knowledge to benefit all of us advanced prostate cancer patients.
Makes sense, since "double blockade" (ADT + 2nd generation ARSIs), after having proved itself in the mCRPC state has now migrated all the way back not only to the mHSPC, but believe it or not, into the high risk BCR state, informed by the recently published, July 2023, Embark study.
Not that this will apply to ADT annihilation (triple therapy: ADT + 2nd generation ARSIs + Zytiga); the "intensification" you are referring to, in the neoadjuvant setting; but annihilation did not prove superiority over double blockade by the highest level of evidence; meta-analysis of phase 3 studies in met PC. So, there appears to be a law of diminishing returns on the low end of the testosterone state, at least for advanced state PC.
Tony, Just curious for how many months after prostatectomy did you continue androgen annihilation? Stated another way, how may months out are you from stopping all hormonal therapy?
I had a 3 month shot of goserelin 1 month before surgery (because of Covid the timing of surgery was uncertain) so effectively I was still on adt for two months after surgery. This was not part of the trial but was happenstance because of Covid. Still, I am glad to have done this as it gave me a little extra chance to kill any stray micromets. T came back 6 months later so that was ok. In fact, your question is one that others are thinking about. there is another current trial out of UC San Diego that compares 6 month neoadjuvant intensive adt before surgery with 6 months of adjuvant intensive adt after surgery.
So, does that mean you are about 2.5 years out from a non-castrate state (T coming back) with no additional therapy and NED; PSA undetectable?
yes
If your Gleason score of 9 is truly reflective of the inherent aggressiveness of your cancer, that you have undetectable PSA at 2.5 years in a non-castrate state, is a very good sign. Even if you BCR, and let's hope not, time to BCR along with subsequent PSA dt calculation after 0.2, are the best indicators of the biologic aggressiveness of your cancer and not pathologic Gleason score; though the latter in univariate analysis is significantly related, in multivariate analysis its significance is overshadowed by earlier 2 metrics.
Curious: Did you get a Decipher molecular study which would be another measure of the biologic aggressiveness of your Cancer, and the first molecular study FDA approved for prostate cancer?
Once you have prostate cancer you never fully kill off all the cells and they can always grow back.
Hello again - I , using the grass cutting analogy and other research, believe the following to be true
1. Alcohol lessens the efficacy of most drugs
2. As far as prostate cancer is concerned "Holidaying from drug regimes" such as those used to block Pca from its main food source testosterone by reducing its available levels in the body is ecouraging the roots to "spread"
3. Radiation does appear to kill cancerous cells in fact it also kills people in high enough doses and can always lead to the risk of creating secondary cancers and very targeted use ( from the inside out - such as internal radiation treatment is obviously preferable - but all radiation can cause secondary cancers .
Unfortuntely for us guys in stage 4 + that has spread past inoperable - the goal is as the Beegees put it " Staying Alive" and I personally love my wife and daughter very much and my life and dont want to lose any time I have with them - so I intend to give "US" the best chance I can .
I hope we can start acheiving cures for cancer soon, for all sufferers, but in the meantime I guess figuratively speaking, grass cutting with the addition of weed killer appears to be the only option to save the lawn for as long as possible !!!!! - me being the lawn.
I sincerley wish all the Pc gang the best with their treatments from stage 1 + and wish everybody a long and industrious life.
I,m 62 right now and stage 4+ and am treated with 800 xtandi and injections of Goserlin and currently PSA unmeasurable for the past 2 years since diagnosis .
I add mushrooms and vitamin D3 and K to my diet and a bit of sensible walking exercise to my week - We all apparently carry the same cells that can and do go cancerous although they normally get told by our immune systems to kill themselves - but some hide and prolifirate - lifestyle and genetics and race play a part in this so lots of research is still to be undertaken.
My request to all the laboratory staff out there " Please find a cure for cancer - for us all " sooner rather than later please !!!!!!
Kindest to all Raoul ( UK)
Incidentaly, I hate not being able to engage in normal marital activities due to loss of libido but have learned to work around this also !!!!!
You have a great attitude Raoul! 62 seems so young to me now. It’s heartbreaking to read posts by men in their 40’s and 50’s with advanced PC. I’m 70 now but optimistic that the disease will remain under control. It seems that research is just on the cusp of finding a cure. The last 10 years brought big changes and new treatments!
Gym-rat wrote -- " Dormant or Dead? ....... So do they die or simply go dormant, or is it a mix of both? "
Beats the crap out of me but I'll take either if It's kicking the can down the road and NOT DOWN THE CLIFF. 😊
youtube.com/watch?v=w00Kab1...
That was hilarious! 🤣 “I have some medical experience. I’m not a doctor, I’m a dentist. Do you think you’re hurt real bad?” 🤣
My question is after I went NED from 3 mets using Erleada and Eligard, why has my immune system not knocked off the micro spots supposedly hiding? After 40 mths, I’m still not willing to stop all ADT to find out. I was a 4+3=7 Gleason and 22.3 PSA @ DX.
If one truly has only 3 mets, that means one technically fits the definition of the recently described state of "oligometastasis". OMPc is being treated with metastasis directed therapy (MDT), with the hope of cure. And if not cure, studies have shown that MDT increases progression free survival, both PSA and radiologic. Whether that translates to overall survival has not been determined yet. Stay tuned. Some Urologists e.g Scholz, and Radiation Oncologists, e.g Rossi; believe they have seen cures.
I am Oligometastatic, 3 local lymph nodes. I had 44 sessions IMRT and am on 2 years ADT. I have asked both my local and MD Anderson MOs what my chances are for a "cure" they have both said 50%.
Is there a test that can detect a single cancer cell? That's the problem, they're too small to detect. My last bone scan in 2022 showed no tumors, does that mean the cells are all dead? No, enough are dead that the rest can't be detected. But even one cancer cell is too many.
When I go back in September for another set of scans I'm hopeful they'll be clear but there's no telling. All you have is today; make the most of it!
Natera. Not tested in prostate cancer, but tested fairly extensively in colon cancer and just recently in breast cancer. What do you think of a detection limit of 1 molecule per 3 ml? Admittedly, the technology has not been vetted in phase 3 studies for either colon or breast cancer; and not studied at all in prostate cancer to date. But, stay tuned.
I think you replied to the wrong person. I know nothing about Natera.
Natera is a biotech company that has 3 molecular tests for cancer: 1 for germ line (what one is born with/inheritied), one for one's tumor tissue, usually from the prostatectomy specimen, and then from the two above tests, they develop a 3rd test, that they proprietarily call signatera.
Signatera is a personalized molecular signature of your cancer. Signatera can detect in your peripheral blood, down to a detection limit of, believe it or not, 1 molecule per 3 ml, molecules produced by your prostate cancer. The molecules are a reflection of your current tumor burden; maybe even better than circulating tumor cells; what you listed as "single cancer cell".
Many doctors don't want you knowing a lot about your condition, they just want to tell you what they think you need to know and send you on your way. If you think about it, saying that the PCa goes dormant is a decent analogy to what actually happens. Whether some dies and some doesn't, or it all goes dormant and comes back, the progression is the same: your PSA goes down for awhile and then maybe comes back. To your doctor, that's all you need to know. Now, if you really want to know how it works, do your own research. I swear there have been some men on these forums over the years that probably knew as much about PCa as the garden variety urologist to whom PCa is just one the things he treats.
There is (recent?) research that inidcates the kidneys produce a small amount of hormones (10%). That may account for some PSA and/or the cancer cells not being totally eliminated. If that is true, surgery may be the least effective treatment. Does that make sense?
Dont mind me, I am a layman. 😊
I'm in the CYPIDES phase 2 trial using a drug that blocks more androgen/hormone sources than Lupron, Zytiga, Xtandi or any of the 2nd generation hormonals.
ODM-208 is a complete blocker of steroid biosynthesis that suppresses the production of all steroid hormones and their precursors that may activate the androgen receptor (AR) signalling pathway. This is particularly relevant in patients with AR ligand binding domain (LBD) activating somatic point mutations, a mechanism of resistance to hormone-based therapies in metastatic castration-resistant prostate cancer (mCRPC). During treatment the patients receive hormone replacement therapy to ensure sufficient adrenal function.
ADT has several benefits, it also has many negative effects.
The benefits
First it can help shrink and make PC more susceptible for radiation to kill it.
Second it can reduce help reduce pain caused by actively growing PC. Although radiation is often used to control pain.
It reduces the testosterone that your testicles produce that your PC uses to be active and grow.
Depending on the ADT it reduces the testosterone produced by other glands as well.
If you're using a drug that prevents your PC from using testosterone. You still have testosterone but the cancer is blocked from using it.
Every prostate cancer is unique. As it is the byproduct of your unique body.
Eventually PC defeats ADT. It becomes resistant to it, so you add another drug and eventually that fails too.
Some members take other approaches to controlling PC. There is estrogen in patch and cream forms, or cycling very high testosterone with low testosterone to name two.
As doctors tell me and what I read over the years. ADT can kill small instances of cancer cells. As the tumors become larger and more complicated they are harder to kill, ADT as it is used currently is not a cure, PC put to sleep by ADT but not killed will reawaken once off ADT.
I learned it has over the years it has taken 16 years for a new discovery to make it through, additional research, clinical trials, and approval processes to be able to become a drug or process available to patients. 97% of trials fail to result in a new approved drug.
Drugs given breakthrough status can do so in less time.
COVID has spread the acceptance of new science and approaches and pushed new approaches years if not decades ahead of where they would have been without the rapid response given to COVID.
Thanks to COVID gene therapy, nanoparticles , immunotherapy, CRISPER, Prime editing and many many variations of these and other understandings will lead to many new therapies for cancer, including PC. Any win against any cancer is a win towards understanding approaches with other cancers.
They just take a short sabbatical to Miami Beach......
Good Luck, Good Health and Good Humor.
j-o-h-n Thursday 06/29/2023 6:40 PM DST
I've wondered the same and seen contradictory info.
Does Lupron affect accuracy of MRI or xrays
To neuter, or not to neuter? That is the question. 😀
Immunotherapy before/after or concurrent with Chemotherapy 
Vacation from Lupron/Zytiga - Temporary or Permanent!
Enzalutamide or Darolutamide
