Steroid Hormones and Progression of Localized High-Risk PCa

[pjoshea13]

New Canadian study below [1].

"The prospective PROCURE cohort was recruited from 2007-2012, and comprises 1766 patients with localized PCa who provided blood samples prior to RP." {radical prostatectomy}

"The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease."

"Testosterone and androsterone levels were higher in low-risk disease."

"In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS {disease-free survival} with HR of 1.47 ... and 1.24 .., respectively."

{Andro & DHEA can be converted to testosterone.}

Yet another study suggesting than androgens are protective.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/307...

Cancer Epidemiol Biomarkers Prev. 2019 Feb 7. pii: cebp.1002.2018. doi: 10.1158/1055-9965.EPI-18-1002. [Epub ahead of print]

A Comprehensive Analysis of Steroid Hormones and Progression of Localized High-Risk Prostate Cancer.

Levesque E1, Caron P2, Lacombe L3, Turcotte V2, Simonyan D4, Fradet Y3, Aprikian A5, Saad F6, Carmel M7, Chevalier S5, Guillemette C8.

Author information

1

Faculty of Medicine, CHU de Quebec Research Center and Laval University [e-mail].

2

CHU de Quebec research Center, Université Laval.

3

Centre de recherche du CHU de Québec-Université Laval, Université Laval.

4

Clinical and Evaluative Research Platform, Université Laval.

5

Surgery (Urology), Medicine, Oncology, McGill University and the Research Institute of the McGill University Health Centre.

6

CRCHUM, Université de Montréal.

7

Urology, Université de Sherbrooke.

8

Pharmacy, Université Laval.

Abstract

BACKGROUND:

In men with localized prostate cancer (PCa) who are undergoing radical prostatectomy (RP), it is uncertain whether their hormonal environment is associated with outcomes. The objective of the study was to examine the association between the steroid metabolome with prognostic factors and progression.

PATIENTS AND METHODS:

The prospective PROCURE cohort was recruited from 2007-2012, and comprises 1766 patients with localized PCa who provided blood samples prior to RP. The levels of 15 steroids were measured in plasma using mass spectrometry and their association with prognostic factors and disease-free survival (DFS) was established with logistic regression and multivariable Cox proportional hazard models.

RESULTS:

The median follow-up time after surgery was 73.2 months. Overall, 524 patients experienced biochemical failure and 75 developed metastatic disease. Testosterone and androsterone levels were higher in low-risk disease. Associations were observed between adrenal precursors and risk of cancer progression. In high-risk patients, a one-unit increment in log-transformed androstenediol (A5diol) and dehydroepiandrosterone-sulfate (DHEA-S) levels were linked to DFS with HR of 1.47 (p = 0.0017; q = 0.026) and 1.24 (p = 0.043; q = 0.323), respectively. Although the number of metastatic events was limited, trends with metastasis-free survival were observed for A5diol (HR = 1.51; p = 0.057) and DHEA-S levels (HR = 1.43; p = 0.054).

CONCLUSIONS:

In men with localized PCa, our data suggest that the preoperative steroid metabolome is associated with the risk of recurrence of high-risk disease.

IMPACT:

The associations of adrenal androgens with progression of localized high-risk disease could help refine hormonal strategies for these patients.

Copyright ©2019, American Association for Cancer Research.

PMID: 30733309 DOI: 10.1158/1055-9965.EPI-18-1002

[pjoshea13]

Nala,

The switch is triggered by high estrogen in many men. The body isn't concerned if your testosterone [T] is high, but if estradiol [E2] is high it lowers T production & increases sex hormone binding globulin [SHBG]. It cannot stop the aromatization of T to E2, so it targets T. The strategy doesn't work for many men & they live thereafter with a dangerous E2:T ratio.

So the metabolic syndrome is the problem for many. From:

"Clinical association of metabolic syndrome, C‐reactive protein and testosterone levels with clinically significant prostate cancer"

"Circulating levels of testosterone and CRP were analysed in the whole cohort of patients according to the individual diagnostic criteria of MetS (I, II, III, IV and V; Table ​Table2).2). Interestingly, testosterone levels were significantly lower in patients that individually met each criterion of MetS compared to those that did not meet these criteria."

ncbi.nlm.nih.gov/pmc/articl...

Developing MetS symptoms due to diet is an unintended form of self-harm fostered by the U.S. food pyramid. And doctors fail to act when patients start to acquire MetS symptoms.

It might be a good idea for men promoting a particular diet, to reveal their own MetS test numbers.

Also of interest, Patrick Walsh discovered that T goes up after surgery, & concluded that the cancer could (further) lower T production.

-Patrick

[Graham49]

Presumably if you are taking the steroid prednisolone as part of the medication to stop organ rejection as I am this is also bad for recurrence of high risk disease?