PCa & Low serum testosterone

[pjoshea13]

New study below.

As I was saying: I believe that there is a case for using testosterone [T] replacement in newly diagnosed men with low T.

"Serum testosterone is a potential marker to distinguish between indolent and aggressive prostate cancer (PCa). The present study aimed to investigate whether low levels of total serum testosterone at diagnosis were associated with aggressive PCa and poor clinical outcomes. In total, 762 non-Hispanic Caucasian men with previously untreated PCa were recruited from The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients were categorized into three groups based on their total serum testosterone levels according to clinical guidelines [low (<230 ng/dl), intermediate (230-350 ng/dl) and normal (>350 ng/dl)]."

Well, 350 ng/dL is now the standard cutoff for hypogonadism. I think that men in the 350-400 range do not have "normal" T. I doubt that many of us were in that range at age 20, 30 or even 40. What we don't get from the study is the T threshhold for no increased risk.

"Testosterone levels significantly decreased as PCa aggressiveness increased... "

"Compared with the normal testosterone group, the low testosterone group had 2.9-fold .., 5.6-fold ... and 72.4-fold ... increased risks of having intermediate-risk, high-risk and metastatic PCa, respectively."

"Furthermore, low levels of testosterone were significantly associated with a 10.7-fold ... increased risk of PCa-specific mortality."

"The results of the present study indicate that low levels of total serum testosterone at diagnosis are associated with aggressive PCa and predict poor PCa-specific survival."

It's a shame that they did not add Free T to the analysis. While there is a correlation between total-T & free-T, the latter might give more accurate results.

-Patrick

ncbi.nlm.nih.gov/pubmed/284...

Oncol Lett. 2017 Mar;13(3):1949-1957. doi: 10.3892/ol.2017.5616. Epub 2017 Jan 18.

Low serum testosterone is associated with tumor aggressiveness and poor prognosis in prostate cancer.

Tu H1, Gu J1, Meng QH2, Kim J3, Strom S1, Davis JW4, He Y5, Wagar EA2, Thompson TC3, Logothetis CJ3, Wu X1.

Author information

1

Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

2

Department of Laboratory Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

3

Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

4

Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.

5

Department of Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China.

Abstract

Serum testosterone is a potential marker to distinguish between indolent and aggressive prostate cancer (PCa). The present study aimed to investigate whether low levels of total serum testosterone at diagnosis were associated with aggressive PCa and poor clinical outcomes. In total, 762 non-Hispanic Caucasian men with previously untreated PCa were recruited from The University of Texas MD Anderson Cancer Center (Houston, TX, USA). Patients were categorized into three groups based on their total serum testosterone levels according to clinical guidelines [low (<230 ng/dl), intermediate (230-350 ng/dl) and normal (>350 ng/dl)]. PCa aggressiveness (low-, intermediate- or high-risk, or metastatic) was compared using multinomial logistic regression. Rates of disease progression, mortality from any cause and PCa-specific mortality were compared using the multivariate Cox proportional hazards model. Testosterone levels significantly decreased as PCa aggressiveness increased (P<0.001). Compared with the normal testosterone group, the low testosterone group had 2.9-fold (OR, 2.92; 95% CI, 1.74-4.90; P<0.001), 5.6-fold (OR, 5.63; 95% CI, 3.14-10.12; P<0.001) and 72.4-fold (OR, 72.40; 95% CI, 20.89-250.89; P<0.001) increased risks of having intermediate-risk, high-risk and metastatic PCa, respectively. Furthermore, low levels of testosterone were significantly associated with a 10.7-fold (HR, 10.68; 95% CI, 1.35-84.44; P=0.03) increased risk of PCa-specific mortality. The results of the present study indicate that low levels of total serum testosterone at diagnosis are associated with aggressive PCa and predict poor PCa-specific survival.

KEYWORDS:

aggressiveness; androgen; progression; prostate cancer; survival; testosterone

PMID: 28454349 PMCID: PMC5403694 DOI: 10.3892/ol.2017.5616

[Sisira]

I am a little bit confused about this. Do you mean to say if I am diagnosed with a PCa of GS 8 or 9 and when my T level is checked, if it is below 350ng/dl ( Low serum T ) I must go for a T replacement. What happens practically is I will be treated with ADT and my T level will be brought down to castration level ( Below 40ng.dl ). So exactly when and how to apply this T replacement theory once you are diagnosed for PCa? Is it before any such diagnosis, as a matter of a routine test? Please clarify.

Thanks

Sisira

[pjoshea13 in reply to Sisira]

Sisira,

If your T was 200, say, the PCa isn't being driven by T. My own belief is that estrogen dominance might be a factor in aggressive progression.

If active surveillance is being followed, consideration should be given to TRT.

Ditto for surgery, IMO.

But for ADT, TRT cannot apply, of course.

Note that Patrick Walsh discovered that PCa lowers T. Why? Because T has an important regulatory role, is my guess. Restoration of T might slow progression. This is important in active surveillance, since low T might identify many in the 25-30% that will otherwise progress.

-Patrick

[Sisira in reply to pjoshea13]

Thanks Patrick. I got the point.

Sisira

[BigRich]

Patrick,

Since I undrestood Casodex was failing; I questioned why the testosterone was falling while the PSA was rising. I was told; what I knew, that Casodex increases the testosterone score, but I wasn't told this was trait of more aggressive prostate cancer. I believe the doctor knew this fact, but was trying to be positive. I would have appreciated the unvarished true. I begin Firmagon this month.

Rich

[pjoshea13 in reply to BigRich]

Rich,

I have mentioned Walsh a couple of times recently. Here is the paper:

ncbi.nlm.nih.gov/pubmed/967...

"Following radical prostatectomy there was a statistically significant increase in serum testosterone, free testosterone,... LH and FSH"

"These findings suggest that the sexual dysfunction associated with radical prostatectomy cannot be explained by androgen deficiency alone. These data further suggest that the normal prostate and/or prostate neoplasm could secrete a substance or substances that give negative feedback control to pituitary gonadotropin secretion."

PCa 'wants' T to be low. It thrives at low T, although there must be enough T to permit growth. The trend as PCa prospers will be T reduction, IMO.

Ironic that ADT is the medical response, but the cancer needs some T so that the AR can get to the nucleus.

In the absence of ADT, TRT might increase PSA doubling time. My feeling, since the "normal" range for T is ridiculously wide, is that the upper third should be the target. Say, >750 ng/dL. With TRT, doctors only aim for >350.

-Patrick

[BigRich]

Patrick,

My Testosterone score is 511 and PSA is 20. I am still trying to ascertain the rational to switch to Lupron after 3 months on Firmagon. I start Firmagon later this month.

Rich