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Low testosterone / PSA failure / risk of death.

pjoshea13 profile image
11 Replies

New study below.

When I started reviewing PCa literature 13 years ago, there wasn't much about testosterone [T]. However, (& my wife still remembers my surprise), normal T levels were not implicated in PCa occurrence or aggressive disease.

Low T, which I tend to think of in terms of estrogen dominance, was growth-permissive.

T below Morgentaler's 'saturation' point - where there is not enough T to bind to every androgen receptor [AR] offers some protection. i.e. partial castration.

None of the studies published in the past 13 years have changed the view that it unsafe to be at the high end of hypogonadal, or the very low end of "normal".

The current study (Dana-Farber, Sloan Kettering, etc, etc.) suffers from the fact that doctors are not interested in T unless they are trying to suppress it. & so we only have "a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) {who} had available testosterone levels at the time of PSA failure."

"After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively.

"Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis."

"These observations provide evidence to support testosterone testing at the time of PSA failure." Well, perhaps a bit late for that, but with a poorer prognosis, a more aggressive treatment seems warranted.

-Patrick

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

Cancer. 2017 Dec 20. doi: 10.1002/cncr.31204. [Epub ahead of print]

Low testosterone at first prostate-specific antigen failure and assessment of risk of death in men with unfavorable-risk prostate cancer treated on prospective clinical trials.

Atkins KM1, Chen MH2, Wu J3, Renshaw AA4, Loffredo M5, Kantoff PW6, Small EJ7, D'Amico AV5.

Author information

1

Harvard Radiation Oncology Program, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.

2

Department of Statistics, University of Connecticut, Storrs, Connecticut.

3

Department of Computer Science and Statistics, University of Rhode Island, Kingston, Rhode Island.

4

Department of Pathology, Baptist Hospital and Miami Cancer Institute, Miami, Florida.

5

Department of Radiation Oncology, Dana-Farber Cancer Institute and Brigham and Women's Hospital, Boston, Massachusetts.

6

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.

7

Department of Medicine, University of California at San Francisco, San Francisco, California.

Abstract

BACKGROUND:

Low testosterone at the time of diagnosis of prostate cancer has been associated with a worse prognosis. Whether this is true and how to define the best treatment approach at the time of first prostate-specific antigen (PSA) failure to the authors' knowledge has not been elucidated to date and was studied herein.

METHODS:

Between 1995 and 2001, a total of 58 men with unfavorable-risk PC who were treated on clinical trials with radiotherapy and androgen deprivation therapy (ADT) had available testosterone levels at the time of PSA failure. Cox and Fine and Gray regressions were performed to ascertain whether low versus normal testosterone was associated with the risk of PC-specific mortality, other-cause mortality, and all-cause mortality adjusting for age, salvage ADT, and known PC prognostic factors.

RESULTS:

After a median follow-up of 6.68 years after PSA failure, 31 men (53.4%) had died; 10 of PC (32.3%), of which 8 of 11 (72.7%) versus 2 of 47 (4.3%) deaths occurred in men with low versus normal testosterone at the time of PSA failure, respectively. A significant increase in the risk of all-cause mortality (adjusted hazard ratio [AHR], 2.54; 95% confidence interval [95% CI], 1.04-6.21 [P = .04]) and PC-specific mortality (AHR, 13.71; 95% CI, 2.4-78.16 [P = .003]), with a reciprocal trend toward a decreased risk of other-cause mortality (AHR, 0.18; 95% CI, 0.02-1.55 [P = .12]) was observed in men with low versus normal testosterone.

CONCLUSIONS:

Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis. These observations provide evidence to support testosterone testing at the time of PSA failure. Given prolonged survival when abiraterone or docetaxel is added to ADT in men with castrate-sensitive metastatic PC and possibly localized high-risk PC provides a rationale supporting their use with ADT in men with low testosterone in the setting of a phase 2 trial. Cancer 2017. © 2017 American Cancer Society.

© 2017 American Cancer Society.

KEYWORDS:

biochemical failure; death; prostate cancer; prostate-specific antigen (PSA) failure; testosterone

PMID: 29266181 DOI: 10.1002/cncr.31204

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Mrkharn profile image
Mrkharn

Maybe if it is low T to begin with, the PCA has already developed some castrate resistance.

pjoshea13 profile image
pjoshea13 in reply to Mrkharn

It is true that some men are already castrate at diagnosis. & 4-5% of men do not respond to ADT. However:

"Low, but not necessarily castrate, testosterone levels at the time of PSA failure confer a very poor prognosis."

So a T of 300 ng/dL (which is nowhere near castrate) is not a good place to be, IMO.

-Patrick

in reply to pjoshea13

I was maybe a shade above that threshold when diagnosed; I was definitely hypogonadal. PSA was only 2.7 however, so that can't be considered 'PSA failure'? The DRE is what steered toward a biopsy. Gleason 8.

BigRich profile image
BigRich in reply to pjoshea13

Patrick,

When casodex monotherapy failed my testosterone score was 704. In October 2017 Zytiga and Prednisone were added to my Lupron. My PSA was 29.7 and Tetosterone was 27; however in December My PSA was 9.5 but my testosterone was 44. Why did testosterone increase?

Rich

pjoshea13 profile image
pjoshea13 in reply to BigRich

Rich,

I wouldn't read much into it. Were the T tests done at different points in the day? Hormones follow a circadian rhythm. Seasonal too. It's not a big variation.

Congratulations on that 704 result. Might help explain the success you have had in staying with us. That's just an opinion.

-Patrick

BigRich profile image
BigRich in reply to pjoshea13

Patrick,

Same time in the morning, test was done. I didn't know about seasonal variation.

Thank you,

Rich

curious-mind profile image
curious-mind

Sorry, I'm a bit confused about the conclusions. Wouldn't it be the case that men on ADT will have castrate levels of T when resistance to ADT sets in? Or is the discussion about low T levels when ADT itself is started?

Arthur

pjoshea13 profile image
pjoshea13 in reply to curious-mind

Arthur,

It is a badly worded paper. The men were not on ADT "at the time of PSA failure", since a high T was associated with a better prognosis.

-Patrick

rnewman751 profile image
rnewman751

Hello Patrick, I hope you are feeling well. What is considered low T? My total is 496, free T is 92, estradiol is 24. Thank you. Wishing you a Merry Christmas and a happy healthy New Year!

Best regards,

Rob

pjoshea13 profile image
pjoshea13 in reply to rnewman751

Hi Rob,

The cutoff for hypogonadism is now commonly 350 ng/dL.

Since the normal T range can go beyond 1,000 ng/dL, depending on the lab, I think of 350-1,000 as a crazy "normal" range. The optimal range must be much smaller & skewed towards the high end, as in youth.

Personally, I think that estradiol [E2] has to be taken into account. So if E2 is 20-25 pg/mL, perhaps low T is 350-400. But if E2 is >35, low T might be 350-450? I have no basis for these numbers, but T is growth-permissive when E2 is dominant.

In your case, E2 is at a good place in the Life Extension range of 20-30 pg/mL. & T at ~500 ng/dL is out of the danger zone IMO.

-Patrick

rnewman751 profile image
rnewman751 in reply to pjoshea13

Thank you

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