Sub-castrate testosterone nadir and clinical outcomes ...

[pjoshea13]

New study below.

"We examined the association of sub-castrate testosterone nadir with PSA response and long-term clinical outcomes in 764 US veterans with intermediate- or high-risk localized PCa treated with ADT and definitive radiotherapy from 2000-2015."

"A testosterone nadir of 20-49 ng/dL was associated with higher 3-month post-radiotherapy PSA compared to <20 ng/dL ... and higher 2-year PSA nadir .... "

"Compared to the <20 ng/dL group, the 20-49 ng/dL group showed higher 10-year biochemical recurrence rates (28.1% vs. 18.3%) and metastasis rates (12.9% vs. 7.8%) ..."

"There was a trend toward inferior PCa-specific mortality for the 20-49 ng/dL group ..."

But is <20 ng/dL really optimal? Will we learn next year that <5 is better, or <1. LOL

-Patrick

ncbi.nlm.nih.gov/pubmed/305...

Int J Radiat Oncol Biol Phys. 2018 Dec 10. pii: S0360-3016(18)34080-X. doi: 10.1016/j.ijrobp.2018.12.001. [Epub ahead of print]

Sub-castrate testosterone nadir and clinical outcomes in intermediate or high-risk localized prostate cancer.

Bryant AK1, McKay RR2, Kader AK3, Parsons JK3, Einck JP1, Kane CJ3, Mundt AJ4, Murphy JD4, Rose BS5.

Author information

1

Department of Radiation Medicine and Applied Sciences, University of California San Diego, CA.

2

Division of Hematology-Oncology, Department of Internal Medicine, University of California San Diego, CA.

3

Department of Urology, University of California San Diego, CA.

4

Department of Radiation Medicine and Applied Sciences, University of California San Diego, CA; Clinical and Translational Research Institute, University of California San Diego, CA.

5

Department of Radiation Medicine and Applied Sciences, University of California San Diego, CA; Clinical and Translational Research Institute, University of California San Diego, CA. Electronic address: [e-mail].

Abstract

PURPOSE:

It is unclear if additional serum testosterone suppression below the castrate threshold of 50 ng/dL improves clinical outcomes in patients with localized prostate cancer (PCa) undergoing definitive therapy.

METHODS:

We examined the association of sub-castrate testosterone nadir with PSA response and long-term clinical outcomes in 764 US veterans with intermediate- or high-risk localized PCa treated with ADT and definitive radiotherapy from 2000-2015. Patients were categorized into testosterone nadir groups based on the minimum testosterone measurement during continuous gonadotropic-releasing hormone agonist therapy (<20 ng/dL vs. 20-49 ng/dL). Outcomes included PSA response (3-month post-radiotherapy PSA and 2-year PSA nadir; multivariable linear regression) and long-term clinical outcomes (biochemical recurrence, metastasis, and PCa-specific mortality; Fine-Gray competing risk regression).

RESULTS:

A testosterone nadir of 20-49 ng/dL was associated with higher 3-month post-radiotherapy PSA compared to <20 ng/dL (ß = 0.16, 95% CI 0.06-0.26, p=0.001) and higher 2-year PSA nadir (ß = 0.12, 95% CI 0.04-0.21, p=0.005). Compared to the <20 ng/dL group, the 20-49 ng/dL group showed higher 10-year biochemical recurrence rates (28.1% vs. 18.3%) and metastasis rates (12.9% vs. 7.8%) persisting on multivariable analyses (biochemical recurrence: subdistribution hazard ratio [SDHR] 1.62 for 20-49 ng/dL, 95% CI 1.07-2.45, p=0.02; metastasis: SDHR 2.19, 95% CI 1.21-3.94, p=0.009). There was a trend toward inferior PCa-specific mortality for the 20-49 ng/dL group (SDHR 1.95, 95% CI 0.90-4.22, p=0.09).

CONCLUSIONS:

Additional serum testosterone suppression below 50 ng/dL was associated with improved PSA responses and lower rates of biochemical recurrence and metastasis in this cohort of localized PCa patients.

Copyright © 2018. Published by Elsevier Inc.

PMID: 30543857 DOI: 10.1016/j.ijrobp.2018.12.001

[Graham49]

Do you know how the lower level of Testosterone is achieved? Is it just a higher dose of the ADT drug or do other drugs have to be used?

[ucladany in reply to Graham49]

Good question. My PSA is at a nadir of 0.119 but my testosterone has gone up from a nadir of 10 to 60 while my PSA continued to drop. What can be done to drop my testosterone?

[Hidden]

When I started this journey with Metastatic Prostate Cancer my Research Medical Oncologist told me that the goal was to get my testosterone at <5.0. I did that. My T was usually 2-3.

I did so well that even a year after stopping Lupron in February 2010, my T never came back. He put me on 4mg of Androgen twice a week. Today using Androgen my T ranges from 450 to 750.

Gourd Dancer

[ucladany in reply to Hidden]

Thank you for your information. Your T is between 450 to 750. What is your PSA level? Just trying to figure this out. My MO told me that any number at 50 or lower was the goal. After reading the research, it seems that 50 is high. Thank you for your help.

[Hidden in reply to ucladany]

I don’t know that I have any answers. While I has a logical and inquisitive mind, I am not a medical nor a scientific research professional. I do know what was shared with me back in 2004. Essentially a my job is to kill your mutated cancer cells and yours is to keep T at 5 or below. Yes, I also have read that 50 is considered castrate and no one can kill cancer completely. Yet, to me these readings were unacceptable to me. I am so fortunate to live near a city that has multiple medical schools and along with professionals in academia and research.

First T. I would think, although limited one method studies conflict, that after Brachytherapy and chased with 25 sessions of IMRT, that Leydig cells had to have been fried. The other aspect is that in a defense mode, the brain tells Leydig cells to re-generate and overload testosterone production. However Lupron/Eligard interferes with the brain. The result is that after years of injections, the brain simply gives up and trains the body to forget about testosterone production.

Second PCa. Metastatic Cancer is systemic and the way to kill cancer cells and cause new growth in place of metastatic lesions, is through chemotherapy. Today most treat with mono therapeutic modes. Only researchers treat in combination of known drugs with cancer killing properties.

In my case it meant two different infusions alternated weekly along with two different orals with one assigned to each infusion drug. Plus daily 30 mg of Prednisone. All five drugs have PCa killing properties. The trial lasted six months consisting of three cycles of six weeks and a two week break between each cycles while still taking the daily dose of steroids. And, of course a continuation of the 3-month Lupron/Eligard injections.

My guy told me that they found out how to kill cancer in 1978. The trick was dosage and combinations without killing the patient first.

I did so well, that my guy convinced me to stop Lupron in 2010 and when T did not come back after a year, to start a low dose of Androgen to restart testosterone production. We stopped after a year to see if I could jump start my body. I could not, so I have been on Androgen ever since.

My PSA remains undetectable. Confirmation? 50 plus PSA tests and 20 plus nuclear bone and CT scans; plus another two pages of blood work tests that he uses for documentation.

He thinks that I am there and has maintained that thought process for eight years. Note: I am one of nine with complete response out of the original testing cohort. The cohort had varying degree of metastatic disease progression. It’s why I espouse early and aggressive treatment while the body is strong and the tumor burden minimal.

Please understand that I am a essentially a guinea pig/mouse and my results are atypical. However, my treatment was atypical as well.

The best of luck in killing this bastard.

Gourd Dancer

[Bako in reply to Hidden]

Thank you so much for sharing yhis information. Where were you treated?

Sounds like you have an EXCELLENT doctor... what is his name?

I need to find an oncologist who specializes and does research as my husband’s current dr is not a prostate specialist. Although we like him very much, we feel much more can be done.

If anyone has a recommendation for a SPECIALIST in the LA or Southern CA area please let me know. Right now we’re on the “standard protocol” with reminders that there is no cure for Mets Pca. This is unacceptable to me.

THANKS SO MUCH!!!

[Hidden in reply to Bako]

I am treated at the Texas Medical Center. In this case Memorial Hermann tied to the Unverity ofTexas Medical School. I started at the same place but only Baylor School of Medicine and Methodist Hospital. I go where my doctor goes.

How I got here. When I developed mets both of my Radiation Oncologist (Air Force friend; one in private practice and the other in academia.) said that anyone could treat me with Lupron. I only had one question and maybe a follow up, “ if you were in my shoes, what would you do?” The answer was straight forward and given by both, “I’d find the best damn Medical Oncologist who specialized in Prostate Cancer; not any other type like breast, lung, etc. preferably one in research.”

The follow up, “Do you know one?” The first in private practice did not; however the second in academia did and further that he sat on a SPORE committee from all of the facilities in the Texas Medical Center and said that he did not know if he could get me in, but he would make the call. Fifteen minutes after I got home, I received a call telling me that the Doctor wanted to see me tomorrow and that he had already seen my scans.

He took two and a half hours with me explains what he could do and what he could not do. I signed up and had a port installed and started a six month chemo-hormone therspy trial. I was most fortunate.

In California, I would start with hospitals associated with medical schools. Go on line and see which doctors are doing research etc. there are a number of people in this group from California. Perhaps they will add to the conversation. Talk Allen is out there and pretty knowledgeable.

GD

[Bako in reply to Hidden]

Thank you so much for responding. Your story validated just what I was thinking. I appreciate your support and advice... this is an awesome site with awesome people. Blessed to have found it. THANKS❤️

[cigafred]

Thanks, I have seen similar study results. My problem is that none of them actually show that doing something more to further reduce T will improve outcomes. Doing something more would probably come with additional side effects and not be covered by insurance, and any improved outcome is a not-unreasonable deduction, but of uncertain validity.