Baseline Serum Testosterone & ADT Outcome.

[pjoshea13]

New study below [1].

Some might think that men with low testosterone [T] would have a head start when beginning ADT. Ironically, "Lower baseline serum testosterone was significantly associated with worse study survival end-points in hormone naïve advanced prostate cancer patients undergoing continuous medical castration."

This is yet another study that associates low T with a poor prognosis.

Note that the cut-off for hypogonadism is 350 ng/dL.

"138 (16.5%) of 838 eligible men had baseline serum testosterone <250 ng/dL."

Looks like the significance of 250 ng/dL here is Morgentaler's saturation model cut-off. i.e. below 250, men were already on 'ADT-lite'.

"The lowest baseline serum testosterone quartile cut-off value was <282 ng/dL (n=206)." i.e. 25% of the men had T below 282.

-Patrick

[1] pubmed.ncbi.nlm.nih.gov/330...

J Urol

. 2020 Oct 9;101097JU0000000000001413. doi: 10.1097/JU.0000000000001413. Online ahead of print.

Does Baseline Serum Testosterone Influence Androgen Deprivation Therapy Outcomes in Hormone Naïve Advanced Prostate Cancer Patients?

Anup Patel 1

Affiliations collapse

Affiliation

1 Consultant Urological Surgeon and 1st Chair EAU Research Foundation Clinical Studies Committee, London, UK.

PMID: 33035140 DOI: 10.1097/JU.0000000000001413

Abstract

Purpose: To study baseline serum testosterone's prognostic value in hormone naïve advanced prostate cancer patients receiving continuous androgen deprivation therapy.

Materials and methods: The study population undergoing continuous androgen deprivation therapy (agonist or antagonist) with 1-year follow-up was pooled for post-hoc analysis from two large prospective, randomized, parallel-arm phase 3b trials (NCT00295750-Global; NCT00928434-USA). Survival end-points were evaluated for baseline serum testosterone effect as a continuous variable, and compared for low (<250 ng/dL) vs. normal (>250 ng/dL) groups based on the saturation model, using Kaplan Meier survival estimates, log rank test, and Cox proportional hazards regression models incorporating established clinically important baseline factors.

Results: Limitations: On intention-to-treat analysis, 138 (16.5%) of 838 eligible men had baseline serum testosterone <250 ng/dL. Key cancer characteristics for low versus normal baseline serum testosterone cohorts were comparable; Gleason sum 7-10 (55 vs. 58%), stage and PSA >20 ng/ml categories (38% each). The lowest baseline serum testosterone quartile cut-off value was <282 ng/dL (n=206). Multi-variable analysis showed a significant baseline serum testosterone effect for all survival end points. For the saturation model low cut-off <250 ng/dL, significance remained for overall (HR 2.24; p <0.02) and progression free survival (HR 1.57; p <0.02), but not for time to PSA progression (HR 1.37; p=0.2).

Conclusions: Lower baseline serum testosterone was significantly associated with worse study survival end-points in hormone naïve advanced prostate cancer patients undergoing continuous medical castration. Future well-designed studies should compare continuous androgen deprivation therapy (the current gold standard) with newer alternatives, to optimize individualized management in these men.

Keywords: Low-testosterone; castration; prognostic; prostate cancer.

[George71]

Yes, that is what Dr. Bob Leibowitz says in his video and it is backed up by the study done recently by Dr. Khera @ Baylor Houston med center..in his video also -- super high T and virtual no T causes PCa to grow the slowest -- and low T causes PCa to grow the fastest.

[pjoshea13 in reply to George71]

Normal-high T (as in young adult males) regulates prostatic growth.

Low (but not castrate) T is growth-permissive in an estrogen-dominant situation.

Estrogen - estradiol [E2] is growth-promoting as ERbeta begins to be replaced by ERalpha.

Which is why a study such as this should also look at the E2:T ratio. IMO

Studies in a number of male health areas find the ratio to be more significant than T or E2 alone.

-Patrick

[George71 in reply to pjoshea13]

pjoshea13,

high T low DHT with E in 20 to 30 range ?? optimal ??

[podsart in reply to pjoshea13]

Do you monitor your E and/or take anything to affect your E2?

I assume a tissue sample is needed to assess how much ERalpha vs ERbeta.

[George71 in reply to podsart]

My Doctor prescribed Arimidex one mg twice weekly -- It seems to be holding E at the desired range of 20/30 -- to prevent T being offset by rising E .. the goal is to get T levels to super high level and keep DHT at low level (Avodart -- 2 times weekly) and have the ratio you had when you were young and when almost no one gets PCa. the slow changing biochemical environment may be contributing to the start of PCa or causing it. Certainly there is now indisputable evidence that super high T slows and/or stops PCa in many people. In many males starting when you are 50 yrs old you start making less and less T -- more DHt and more E every decade the rates of PCa increase -- 50% when 50yrs old have PCa -- 60% when 60 -- 70% when 70 and so on.

[George71 in reply to George71]

Men on nothing but finasteride to lower DHT levels were shown to have 25% less PCa over 8 year study.

[podsart in reply to George71]

Yea, I’m on avodart and have Supra T as SE from xtandi. The e2 measurement and use of arimidex is interesting

[George71 in reply to podsart]

Now that is different -- xtandi actually blocks cells from getting testosterone -- in your case your body may keep making T (if you are not on lupron) but still cant use it... but If you were only on lupron -- and not xtandi you could supplement T and your body could use it... intermittent ADT... when on the off cycle T works even if you stay on lupron --- but unable to use T at all if on Casodex or xtandi -- you have to stop them to be able to use T and be on an off cycle..

In my case I am not on any ADT of any kind that interferes with making / using / or lowering T --- so I can use all the super T my body makes or I inject / rub on etc. I only take enough Avodart to lower DHT -- but not stop all production or use of DHT. Same with E only take enough Arimidex to lower range.

[Justfor_ in reply to George71]

Do you know your baseline T to E2 ratio, i.e. before taking measures to increase the numerator and decrease the denominator?

[Tommyj2 in reply to podsart]

Am I reading this correctly George...that Super High T with controlled DHT is a _ treatment_ for PCA.... ?? I’m a bit confused...is this approach being used with any frequency anywhere??

[pjoshea13 in reply to podsart]

When I alternated between 3 months castrate & 3 months high-T, I occassionally tested for E2 in the T phase. Mostly I took 0.5 mg Arimidex 3 times weekly - but only in the T phase.

With my BAT 2-month cycle I don't feel concerned about E2 levels during the brief T phase.

-Patrick

[podsart in reply to pjoshea13]

thanks

[billyboy3]

Part of the problem is in NOT trying intermittent hormone therapy first, so that you can take a break, and recharge the body and your testosterone level.

[noahware]

It makes sense in the context of a BAT concept that the more drastic the change in hormonal milieu, the more "shock" that PC cells might experience. A change of T from 700 to near-zero is more drastic than a change of T from 200 to near-zero.