Hormone dependent cells vs. hormone independent cells

Not to my knowledge. I believe the only way to tell is to go on HT and if psa drops to .05 and stays there for a period of months then most or all of the cells are dependent. You also have the testestorone levels at casteration levels for this to occur, I believe this is <20.
JT

Follow up question - Is it the hormone dependent cells learns how to live in time, the hormone independent cells multiply, or both that causes HT to become ineffective?

I believe that about 30% of all advanced PC is compsoed of primarily of dependent cells. That's why approximately 30% of patients given HT will oly go through one course of it and never have psa rise again. The rest is a mixture of dependent and independent cells and depending on the proportion will determine how long HT is effective. There is reason to believe that if HT is started early enough while the independent cells are low in number and they have not yet mutated and built up a resistance to HT that HT may also kill these.
JT

Jerry, regarding questions on treatment of advanced PC, this commonly heard reminder should be re-issued:   one size does not fit all.   Individualized treatment plans will depend largely on the answers to questions which help characterize the biology of the individual case .   What are the site(s) of metastasis?   What was/is response to prior and current treatments?   What are the testosterone and PSA levels?   Is PSA progression the only evidence of therapy failure, or are there other symptoms?   Is the case androgen-independent (AIPC, which implies the potential for responding to a secondary hormone measure) or hormone-resistant (HRPC, patients who do not respond to various hormone treatments or who have progressed following these treatments and would not be expected to respond to another)?   So, t he optimal treatment plan for each case will vary ...this is important to keep in mind. To try to address your specific question more directly... Jerry L. said... Follow up question - Is it the hormone dependent cells learns how to live in time, the hormone independent cells multiply, or both that causes HT to become ineffective? I assume that this question is just for your own personal interest and curiosity since one cannot affect this, but here’s a copy/paste of a recent (2009) abstract which I believe addresses the question: Molecular biology of androgen-independent prostate cancer: the role of the androgen receptor pathway. Abstract Prostate cancer (PC) cells express the androgen receptor (AR) and need the presence of androgens to survive. Androgen suppression is the gold standard first-line therapy for metastatic disease. Almost all PC patients initially respond to hormonal therapy, but most of them gradually develop resistance to castration. There is evidence that these tumours that are considered castration-resistant continue to depend on AR signaling. Several mechanisms that enhance AR signaling in an androgen-depleted environment have been elucidated: (1) AR mutations that allow activation by low androgen levels or by other endogenous steroids, (2) AR amplification and/or overexpression, (3) increased local intracrine synthesis of androgens, (4) changes in AR cofactors and (5) cross-talk with cytokines and growth factors. Today, there are a number of novel agents targeting the AR signalling pathway under development, including more effective antiandrogens; inhibitors of CYP17, inhibitors of HSP90, inhibitors of histone deacetylases and inhibitors of tyrosine kinase inhibitors.         Reference:   http://www.ncbi.nlm.nih.gov/pubmed/19155198 , or http://www.springerlink.com/content/a275n01140k0261p/fulltext.pdf    (challenging to read)   So, in other words, this report says there are several theories on how it happens, but no complete, 100% certainty.   Post Edited (Casey59) : 12/29/2010 2:41:32 PM (GMT-7)

I have a related question that hopefully one of our experts can answer.

If one has had curative treatment such as seeds and IMRT and is on HT because the cancer was very aggressive, how do we correlate PSA with PSA for someone who does not go on HT. This is a question that obviously pertains to my case and I have simply not been able to get a good answer. Sure would appreciate it if someone could direct me to some relevant literature on this issue. My PSA has dropped to a fairly low number (0.013) and may be still going down, but how meaningful is the number given that I have been on HT for over a year.

Sancarlos

Sancarlos said... I have a related question that hopefully one of our experts can answer. If one has had curative treatment such as seeds and IMRT and is on HT because the cancer was very aggressive, how do we correlate PSA with PSA for someone who does not go on HT...   Sancarlos, I’m no expert but I’ll attempt to give an informative answer.   I should also say that I am not a doctor…if I don’t say it every once in a while, someone else jumps in to remind me.   Saying that one is “on HT” can mean multiple things.   Most commonly in advanced PC cases, going “on HT” means a double- or triple-blockade approach in which the goal is to reduce the PSA as low as possible …in fact, down to an ultra-sensitive PSA test level of undetectable (or around 0.05ng/mL) and keep it there as long as possible (and hope it stays low for 12 months or more after going “off” the blockade).   A very low nadir, held for a long time, yields the best prognosis.   The information you provided isn't crystal clear, but f rom what you wrote I think you have been prescribed a single adjuvant HT component to supplement your radiation treatments; probably finasteride...this is a different case than described in the paragraph above.   Finasteride (Proscar) or dutasteride (Avodart) are often given for prostate enlargement, or as part of an adjuvant HT regimen.   These drugs prevent the conversion of testosterone to dihydrotestosterone.  The theoretical basis for using finasteride to prevent PC is that almost all PC cells are responsive to male hormones (androgens).   Because androgens might stimulate the change of normal prostate cells into PC cells and stimulate the growth of PC after they have become malignant, then, the argument goes, if finasteride (or dutasteride) can slow or prevent the production of dyhydrotestosterone, they might slow or prevent the development and progression of PC.   The PSA levels in men taking finasteride alone usually decrease by 30% to 70% after about one year.   Perhaps you’ve already heard the general rule of thumb about the need to “re-baseline” one’s PSA by 50% if taking finasteride, and I suspect this was the root of your question.   Does this answer your question?

TC-LasVegas said...
What I have seen as a layman is those cases like this one that i have mentioned before. A 53 year old man having an RP with orchiectomy in 1981. Gleason unknown. 29 years later he has Gleason 10 invasion in his bladder. Tony

Tony, I, too, was a bit baffled by how you described this case; although, I suspect it might have been imprecisely conveyed to you and you are simply passing on what you heard.  But if not, then I'm open to new understanding.

Your friend had a radical prostatectomy (RP) and orchiectomy in 1981.  In 1981, Gleason scoring was, I guess, less ubiquitous than today, and so it was then "unknown". 

Over time, apparently, your friend's PC metastasized to his bladder.  This is where I get lost, because you report this as a "Gleason 10 invasion in his bladder."  My understanding is that Gleason grading is done only to prostate tissues found in either a prostate biopsy or RP specimens...but specifically not of metastasized PC cells in other organs.  If your friend reported to you Gleason 10 cells in is bladder, this would be the first time I've heard of such a thing...but like I said, I'm open to new understanding.

Can you please clarify?  Just trying to see if there is something new to learn here.  thanks

 

Casey59 said...
Over time, apparently, your friend's PC metastasized to his bladder. This is where I get lost, because you report this as a "Gleason 10 invasion in his bladder." My understanding is that Gleason grading is done only to prostate tissues found in either a prostate biopsy or RP specimens...but specifically not of metastasized PC cells in other organs. If your friend reported to you Gleason 10 cells in is bladder, this would be the first time I've heard of such a thing...but like I said, I'm open to new understanding.

I agree it does sound unusual. But I think in such cases there could be a biopsy or surgery, and since the cancer is still PCa, the grading could have arisen from that.

Mark Moyad just made this statement in the Paact Newsletter page 2 top middle right paragraph. 'Tumors make their own testostorone despite men having castrate levels of 'T' from LHRH drugs and now there is a drug to keep certain tumors from feeding itself so to speak!' (talking about Abiraterone as to this drug).

I have not heard this before that tumors could make their own 'T' or perhaps version of a 'T' as to being fed????? Anybody have other references to such??? We understand about things being able to morph and DNA ploidy anaylsis has been shown to change or be at different levels, even in comparatively same stats looking patients.

This area is the multi-million dollar questions! I would presume.

San- I have been there and done that and went off all drugs for 1 year as my own test and done intermittent useage with DES (2005) after 2 ys. of ADT3 (2002-2004) and I had worse overall stats than you have. Done pretty well considering my starting points. One way to know is eventually go off drugs and get psa tests done monthly (as I did such to see what and when and velocities). This can tell you a thing or two about how aggressive it might actually be...of course would be at your own risk or done with doctors blessings.

This is the Twilight Zone of PCa....where does one stand in this limbo land? It varies alot and from patient to patient. I doubt your psa would rise all that much in one year is my s.w.a.g. estimate.

http://advancedprostatecancer.net/

Click on the "understanding CRPC " link for the video. This video is produced by the J & J subsidiary responsible for commercialising Abiraterone.

Hi Casey,

Thank you for your very informative and interesting answer to my question.

I had also rather assumed that the PSA for my situation at this time would not matter all that much, at least so long as it was not increasing but you have supplied some information that make it easier to understand.

Have a Wonderful New Year.

Sancarlos