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, the optimal treatment plan for each case will vary...this is important to keep in mind.
To try to address your specific question more directly...
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.
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)
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 from 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?
Post Edited (Jerry L.) : 12/29/2010 6:19:10 PM (GMT-7)
Hi again, Sancarlos.
After a quick reminder that I’m no expert, I think that the real answer to your question is: the game has changed (now that you are “on” ADT3), and so it (relating your “on” PSA test result to an “off” result) doesn’t really matter. Allow me to explain what I mean.
First of all, you have a challenging case. Gleason-9, six-of-six cores positive. No signs of metastasis to your bones (or elsewhere, but most commonly (70%) bones), which is great, but your doctor will undoubtedly watch this closely over the upcoming years while taking proactive steps (via ADT3) to keep it that way…but you are at higher risk than most typical PC patients of this happening somewhere down the road.
The goal of your triple-blockade is to cut-off the sources which feed prostate cancer, and to do so for as long possible because (as discussed earlier in this thread) the cancer will otherwise (most likely) eventually become hormone-resistant. Many men have been very successful on ADT3, and more specifically on the “intermittent” IADT3 for many years…especially those men who also embrace serious lifestyle modification in the areas of diet, exercise and stress reduction...other sources which also "feed" your prostate cancer. Dr. Charles “Snuffy” Myers is one of the leading experts in this area, if you wanted to research more.
So, you want to beat-down your PSA (which is the marker for disease progression). This chart (click on this IMAGE) is in Dr Stephen Strum’s publications (online, and I think also in his book), and shows visually the “Treatment Roadmap” of what you are trying to accomplish on ADT3. (a) Knock down the PSA by starting ADT3, (b) hold it down for a while on ADT3, (c) typically stop ADT3 and monitor how long the PSA stays down, (d) eventually watch it slowly rise, and then (e) when it crosses a threshold (5 ng/mL shown on the Strum chart, but more recently I’ve heard of 10 ng/mL) restart (“intermittent”) ADT3 again to repeat the cycle. Here’s a PCRI article from Strum; it’s from 2000, but still good. LINK
I’m going to politely disagree with zufus’ characterization of this being a “twilight zone” or “limbo land”…I think it typically follows a relatively predictable pattern (shown in the Strum chart), with some natural variation in the un-labeled x-axis (time).
My point here for you Sancarlos, which I hope is now more clear, is that it really doesn’t matter what your PSA might be without ADT3…what matters is if and when it rises after stopping ADT3 (the ADT3 "Treatment Roadmap").
I hope this helps. I undoubtedly covered some points in this topic which you were already familiar with, but did so in hopes that others less familiar with your type of case might also benefit & learn from reading this post in the future.