Role of free testosterone levels in mCRPC.

[pjoshea13]

New German study below.

"Despite the fact that free testosterone (FT) is the biologically active form, it is common practice that androgen suppression is monitored via total testosterone levels only."

Yes, crazy! Dr. Myers goes further. Who cares what T is, when DHT is driving proliferation.

Anyway, in the new study:

"Despite the fact that all patients were undergoing androgen deprivation, the mean serum FT levels for each patient varied; the mean FT concentration in the cohort was 0.328 pg/ml, ranging from 0.01-9.1 pg/ml."

"A notable difference with regard to CSS {cancer-specific survival} was observed for patients with regard to serum FT concentration; CSS was significantly longer for patients with a serum FT level below the cutoff level (43.6 vs. 17.3 months, respectively ..."

Note that free T is usually calculated (estimated). Normally, 1-2% total T is free. About half of the remainder is loosely bound to albumin, & is considered bioavailable. The rest is bound to SHBG (sex hormone binding globulin) & unavailable. The calculation assumes an average albumin level. SHBG is the only true variable used, other than total T.

I don't know how accurate that approach would be for men on ADT. (& I think that men using estradiol for ADT would have unusualy high SHBG numbers.)

Why not just measure DHT?

-Patrick

ncbi.nlm.nih.gov/pubmed/281...

Oncol Lett. 2017 Jan;13(1):22-28. doi: 10.3892/ol.2016.5392. Epub 2016 Nov 17.

Role of free testosterone levels in patients with metastatic castration-resistant prostate cancer receiving second-line therapy.

von Klot CA1, Kuczyk MA1, Boeker A1, Reuter C2, Imkamp F1, Herrmann TR1, Tezval H1, Kramer MW3, Perner S4, Merseburger AS3.

Author information

1Department of Urology and Urological Oncology, Hannover Medical School, D-30625 Hannover, Germany.

2Department of Hematology and Oncology, Hannover Medical School, D-30625 Hannover, Germany.

3Department of Urology, Campus Luebeck, University Hospital Schleswig-Holstein, D-24105 Luebeck, Germany.

4Pathology Network of the University Hospital of Luebeck and Leibniz Research Center, D-23528 Borstel, Germany.

Abstract

A range of new treatment options has recently become available for patients with advanced metastatic castration-resistant prostate cancer (mCRPC). Androgen deprivation therapy (ADT) with luteinizing hormone-releasing hormone is continued when performing chemotherapy or androgen deprivation with new second-generation therapeutic agents such as enzalutamide or abiraterone acetate. Despite the fact that free testosterone (FT) is the biologically active form, it is common practice that androgen suppression is monitored via total testosterone levels only. The aim of the present study was to evaluate the role of FT as a prognostic biomarker for cancer-specific survival (CSS) and its feasibility as an ADT monitoring biomarker in patients with mCRPC for the first time. The requirement for continued ADT in mCRPC patients is discussed within the basis of the current literature. A total of 34 patients with continuous measurements of FT levels and mCRPC status underwent therapy with docetaxel, abiraterone acetate, enzalutamide, cabozantinib, carboplatin or cabazitaxel. Data were obtained from the Departments of Urology and Urological Oncology, Hannover Medical School (Hannover, Germany) between March 2009 and April 2014. A cutoff point of 0.5 pg/ml was used to discriminate between patients according to FT levels. Statistical evaluation of CSS was performed by applying Kaplan Meier survival estimates, multivariate Cox regression analyses and log-rank tests. The median age of all 34 patients was 72 years (range, 51-86 years). The mean follow-up interval was 16.1 months (range, 0.7-55.6 months). Despite the fact that all patients were undergoing androgen deprivation, the mean serum FT levels for each patient varied; the mean FT concentration in the cohort was 0.328 pg/ml, ranging from 0.01-9.1 pg/ml. A notable difference with regard to CSS was observed for patients with regard to serum FT concentration; CSS was significantly longer for patients with a serum FT level below the cutoff level (43.6 vs. 17.3 months, respectively, P=0.0063). Upon multivariate Cox regression analysis, the mean FT concentration during treatment remained a significant prognostic factor for CSS (hazard ratio, 1.22; 95% confidence interval, 1.03-1.43; P=0.0182). In conclusion, in patients with mCRPC, the serum FT level is a strong predictor of CSS in patients under therapy with second-line anti-hormonal therapeutic medication and chemotherapy. It may be concluded that FT levels should be included into the routine control of androgen suppression while under treatment with ADT and second-generation hormonal therapy.

KEYWORDS:

abiraterone acetate; androgen deprivation therapy; enzalutamide; free testosterone; luteinizing hormone-releasing hormone; metastatic castration-resistant prostate cancer

PMID: 28123517 DOI: 10.3892/ol.2016.5392

[PubMed]

[Neal-Snyder]

Patrick & Nalakrats,

We're still traveling but I emailed my Kaiser med onc asking for a DHT test when we get home & I go in for tests on 3/23. He wasn't familiar with any clinical trials (always what he relies on) showing that DHT is a better test than T for PCa patients.

So I searched this site for DHT, & didn't find a post primarily on DHT. If there is one, the search function is deficient.

My med onc is young & was only assigned to specialize in prostate, bladder & testicular cancers a few months ago. He'll be open to the idea, but only if I can show him the evidence.

Is there a post on DHT & clinical trial outcomes? Or can you point me to any such study outcomes? Or any kind of research evidence that DHT is a better test than T for us guys?

Thank you!

Neal

[Neal-Snyder in reply to Neal-Snyder]

Re-reading your post, Nalakrats, I suppose evidence of the value of blocking the formation of DHT could also be useful with my med onc. Thanks.

Neal

[Neal-Snyder in reply to Neal-Snyder]

Patrick, I think I remember you saying that PCa feeds on DHT, not T. If that's right, a citation for that might be what I need for my med onc. It doesn't sound like he's aware of that.

[Neal-Snyder]

Thank you, Patrick.

Neal

[Neal-Snyder]

Thank you, "Nal." Yes, I can definitely see you have a concern for the subject. I'll call BioResponse for sure in a couple of weeks. We get back to the US of A on 3/20.