Mortality Probability after first PSA rise vs non-castrate testosterone levels (low vs Normal)

[janebob99]

Here's a plot from Atkins (2018) that shows the Percent risk of Prostate Cancer-specific Mortality versus time following a first PSA failure, for two different non-castrate testosterone levels (Low-T and Normal-T). The low testosterone levels are: median = 162, range = 120-236 ng/dL. Normal T is 400-700 ng/dL.

The Cohort is "Unfavorable Risk", according to the paper.

The plot shows that having normal T levels are protective, when compared to "Low" testosterone levels (120-236 ng/dL).

At 5 years after first PSA failure, the prostate specific mortality rate is about 7% for normal T, versus 58% for "Low" T. That's a huge difference, which only gets larger with longer time.

The paper also reports that the PSA doubling time is 2.8 months for Low-T and 10.6 months for Normal-T. Also, the median survival time is 4.1 years for Low-T versus 7.6 years for Normal-T. These are significant differences!

These results suggest that doing TRT after a first PSA rise might be very effective at prolonging life.

The paper doesn't mention this, but it would be interesting to find out if this Cohort was castration-resistant or not. Likely, they are, because the "Low-T" levels are non-castrate levels.

pubmed.ncbi.nlm.nih.gov/292...

[Justfor_]

Who needs TRT. Just a bit of Bicalutamide and the endogenous T will go up 50 -100%.

[Scout4answers in reply to Justfor_]

Interesting, can you elaborate on this. What about bicalutamide allows, or better yet causes, T to rise?

[Justfor_ in reply to Scout4answers]

Feedback loop disruption/manupulation. Some parts of the body sense a reduction in T supply, due to the Bicalutamide action and in response stimulate the brain to boost organ production. In conjunction with Avodart, that works similarly but to a lesser degree, my baseline T of 800-900 has spiked to 1700-3200.

[janebob99 in reply to Scout4answers]

Sorry...I don't know anything about biclautamide action...

[Scout4answers]

pubmed.ncbi.nlm.nih.gov/384...

Does this contradict your study?

[janebob99 in reply to Scout4answers]

Good question. Unfortunately, I don't have access to the full paper. If you have the full paper, could you send it to me?

I could speculate as to the result, i.e., that patients who recovered their testosterone (presumably after stopping ADT) quickly relapsed more quickly than those men whose testosterone stayed low for a longer time. I believe that it all depends if you are in the hormone-sensitive regime (hsPC) or the castration-regime (CRPC). The testosterone dependence flips the other direction when crossing this boundary.

If you are still in the hormone-sensitive regime, then lower values of testosterone will be strongly associated with lower values of PSA and, hence, have longer times to PSA "failure / recurrence" (rise after a nadir). Conversely, if your testosterone rises quickly after stopping ADT, then your PSA will also rise more quickly and, hence, reduce the time to reach PSA recurrence. That's exactly what your paper shows. So, I have to conclude that these men were in the hormone-sensitive regime (non-castrate resistant PC).

The opposite trends would hold true for castration-resistant cancer, which occurs after non-castrate resistant PC stops. The plot that I posted above has two different levels of testosterone, "LOW" and Normal. The low value is not a castration level. Rather, it ranges from 120-236 ng/dL. That's not a castration level (< 50 ng/dL), despite the fact that they call it "LOW". I would have called it "Low-Normal", not "Low". The fact that the "Low" range is so high indictates that these men have been off of ADT for a long time, during which their cancer may have become castrate-resistant. Or, that their length of ADT (?) was sufficiently long to switch to being castrate-resistant. In that regime, lower testosterone was associated with worse outcomes...the opposite of your paper.

No one understands why higher testosterone is more protective in the castrate-resistant regime. Perhaps someone could explain that? It's likely related to the Morgentaler Saturation Model somehow.

Bob

[janebob99 in reply to Scout4answers]

Addendum...

I was talking to my wife about your question, and the thought occurred to me that the results of the Bipolar Androgen Therapy (BAT) method are consistent with my hypothesis. In BAT, they give periodic super high doses of testosterone injections once every few months. This super-high T exposure "resets" the castration-resistant cancer cells and turns them back into hormone-sensitive cancer cells (whereupon they respond well to testosterone castration (ADT)). The cycle is repeated many time, repeatibly converting the cells back and forth, and preventing PSA from rising uncontrollably to high levels.

BAT kinetics

[Scout4answers]

This super-high T exposure "resets" the castration-resistant cancer cells and turns them back into hormone-sensitive cancer cells

Not sure this is the case as it would follow that BAT would continue to work forever which does not seem to happen in the real world. I wish that your statement was in fact true as that would keep us from progressing in to a Metastatic state.

[janebob99 in reply to Scout4answers]

Good point.

I need to read up more on BAT therapy, to better understand it. You can see in the plot I posted that the lower value of PSA is slowly rising after many BAT cycles. Note that the Y-axis is a log scale.

So, BAT's not a perfect treatment. But, it works pretty well overall, and they are still learning about it and how it works.

I'm sure that Morgentaler's Saturation Model can explain, at least partially, how/why the BAT works.

Bob

Morgantaler's Saturation Model

[Scout4answers in reply to janebob99]

We agree , BAT is one of the tools that is on my list should PSA rise again. I view it as a QOL enhancer not a cure.

[jackwfrench in reply to Scout4answers]

Same for me. I would like to know more about how quickly to administer it on a PSA rise (maybe doubling within 9 months?) and where to get treated so we are prepared, how to manage the process, and how much time it likely can bring us!

[janebob99 in reply to jackwfrench]

Are you talking about BAT therapy? If so, go to Dr. Sam Denmeade's website at Johns Hopkins University. He invented the BAT protocol. And, it's cheap !

hopkinsmedicine.org/profile...

[jackwfrench]

I am only castrate sensitive and Sam has nothing going on BAT with that. Thanks though.

[janebob99 in reply to jackwfrench]

You're welcome.

I may have misunderstood your earlier post that has questions...

You wrote:

"Same for me. I would like to know more about how quickly to administer it on a PSA rise (maybe doubling within 9 months?) and where to get treated so we are prepared, how to manage the process, and how much time it likely can bring us!"

What is "it"?

Do you have a plot of your PSA versus time that you could post? Or a table of numbers, and I could make a plot for you. 😀

Bob

[jackwfrench]

"same for me" indicating that it is on my list - ie. I want to be ready when PSA climbs again.

[Mike58]

OK, this converstaion is way above my pay grade and hard to follow - for me anyhow. But here are 3 questions, where the answers may help me understand a bit better.

1: What is meant by PSA failure?

2: Why would one have low testosterone at time of DX and what is considered as Low?

3: What is TRT?

Yep, I'm a dummy but I wonder how many like me, liked this post but just couldn't fully grapple with a lot of the terminology.

[janebob99 in reply to Mike58]

You're not a dummy!

There are no bad or dumb questions in this Forum. You're only dumb if you don't ask, IMHO.

1. After "curative" treatment (radical prostatectomy) RP or radiation treatment (RT), the PSA drops to very low levels (<0.5). But, in 30-50% of men, after some residence time (which can be years), they can experience a recurrence in Prostate Cancer (PCa). When this happens, the PSA starts to rise again from the low point (nadir) after RP or RT. If it rises more than 2 points, or if it has a PSA doubling time shorter than about 8-9 months, then this indicates a tumor(a) is likely growing somewhere in the body (inside the prostate or prostate bed, NS/or outside of the prostate). That PSA rise above 2 points is called "PSA Failure". So, if your PSA nadir was 0.5, then PSA Failure occurs at PSA > 2.5.

2. If someone had untreated hypogonadism at time of diagnosis, then their baseline T would be low (less than about 200 ng/dl). Also, older men naturally have lower T levels (if not supplemented), and their natural baseline could be less than 200). For reference, the official definition of castration is T < 50 ng/dl, but some doctors strive to reach sub-castrate levels of T < 20 ng/dl.

3. Testosterone Replacement Therapy (TRT). I supplement T every day because I have hypogonadism.

Bob

[Mike58 in reply to janebob99]

Just a follow-up question. My T level at DX was 18.6 nmol/L - what would that be in the USA measurement system? - Here in Australia they say the reference range would be between 6 - 28.

[janebob99 in reply to Mike58]

The conversion between nanomol/L is as follows:

1 nanomol/L = 28.8 ng/dl.

So, your value of 18.6 nano mol/L is equivalent to 536 ng/dl in the US system, which is right in the middle of the range of 300-700 ng/dl.

[Mike58 in reply to janebob99]

Excellent, thanks Bob.

[Mike58]

Thankyou Bob, that is an excellent answer and clears up all my uncertainties about what seemed to be a complex post. I'm ever learning about this ever evolving and intricate disease.

Thanks again 👍