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Advanced Prostate Cancer
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Shifting the Paradigm of Testosterone Replacement Therapy in PCa.

New paper from Hopkins. Indicative of the way the wind is blowing?

"Historically, testosterone and prostate cancer have been demonstrated to have a positive association leading providers to forgo testosterone replacement therapy (TRT) in men with concurrent histories of hypogonadism and prostate cancer. This paradigm has been gradually shifting with our evolving understanding of the relationship between testosterone and prostate cancer and the gaining popularity of the saturation model. Newer data suggests improved quality of life for men with hypogonadism after TRT leading to a more tempered view of the effects of this treatment and its risk in prostate cancer. As more reports emerge of TRT in men who have either undergone definitive treatment for prostate cancer or are on active surveillance, some providers see a role for TRT in these patients despite non-consensus in clinical guidelines. It is critical that we examine evidence currently available, while we await more rigorous data to emerge."

ncbi.nlm.nih.gov/pubmed/296...

-Patrick

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The article confines itself to the two disease states: active surveillance and post definitive treatment. These are the two edges of the illness. And note that the authors do not include Denmeade or Isaacs, even though the authors are at johns Hopkins. Any idea who they are, or their claim to fame?

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The author is "MA Bell", would you believe.

Arthur L. Burnett, the team leader, I suppose, was easier to find:

"A frequent contributor to the medical press, Dr. Burnett has written more than 150 original peer-reviewed articles, along with numerous additional articles, editorials, and book chapters, relating to his biomedical research and clinical activities. His work has appeared in many prominent journals such as Science, Nature Medicine, Proceedings of the National Academy of Sciences, Journal of Urology, Urology, and Journal of Andrology. A Fellow of the American College of Surgeons, Dr. Burnett is also a member of the American Urological Association, Sexual Medicine Society of North America, International Society for Sexual Medicine, Society of Genitourinary Reconstructive Surgeons, Society for Urodynamics and Female Urology, and the Society of Black Academic Surgeons. He has sat on various advisory committees including the Urology Study Section, National Institutes of Health Center for Scientific Review and FDA Advisory Committee for Reproductive Health Drugs."

I imagine that Denmeade gets credit in the full text.

Also, since there is mention of the "saturation model", Morgentaler must be mentioned too.

-Patrick

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I had a phone consult with Dr Morgentaler re: use of TRT for my Gleason 9 stage pt3bN0M1 case. I say “N zero” because RT seems to have eradicated PCa in my pelvic lymph nodes. He said he only used TRT on men like me if patients were totally miserable with low T and were willing to take the risk .

Bob

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Thanks for the article Patrick. I am probably one of those reported. I also will state my results are atypical of a person who was treated for Stage 4 Metastatic Prostate Cancer.

As stated before, on May 4, 2004, I was officially diagnosed with mets to L2 & T3, PSA - 30.2. I underwent a six month chemotherapy-hormone trial two months later. I received my last hormone injection on February 11, 2010. On January 11, 2012, I started TRT with 4 mgs of Androgen twice a week.

Since starting TRT, I have had 25 PSA, along with about three pages of other tests and one nuclear bone and CT scans on November 15, 2016. All tests have continued to reflect no indication of Prostate Cancer. My last blood draw on March 20, 2018 reflected - PSA, <0.1 and T, 383.7. Note -T has been as high as 733.4 during the six year period of TRT. Since T has a very short half-life, the range depends on what day testosterone was applied compared to what day that blood was drawn. My next schedule blood draw is July 17, 2018.

At age 71, Quality of Life has improved tremendously. In fact, my QOL has increased greatly through this whole PCa ordeal starting at age 55.

GD

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If you are/were "Stage 4 Metastatic Prostate Cancer" then you are not in the group of patients that the article is talking about. It asserts it is talking about prostate cancer

"in men who have either undergone definitive treatment for prostate cancer

or are on active surveillance".

Since you are not on active surveillance and since there is no definitive treatment for metastatic prostate cancer, you cannot be "one of those reported on"; that is, whose data is used to support the conclusions of the article.

Your case is possibly for another article.

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Interesting read Martin..... europeanurology.com/article...

GD

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I don't find the word confusing.

My understanding has been that a therapy is "definitive" when it is given with curative intent - when there is good reason to believe that this therapy offers a good chance to eliminate the disease, and is being given with that intention. Some of these treatments have a 10 year remission rates above 95% and upto 99%. HDR seeds is one of these.

The phrase primary treatment may mean treatment to the primary - ie the prostate.

It's fine enough, but also open to confusion, as primary also means first.

Patients are eligible for Active Surveillance only when they are delaying a therapy that is definitive; definitive in the sense that there is a good expectation that it will resolve the prostate cancer, even if delayed for a while to see if that treatment is (even) necessary.

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I am curious as to what your experience is as to the half-life of testosterone. And similarly your experience, if you have it, to the PSA level. I find after a testosterone shot that the fall in PSA is quite slow, but I have no sense of what the typical experience is.

I am interested in the decay rate because I want to compare it to the original decline in PSA after my initial chemo/ADT treatment.

A "typical half life" might be useful in the calculation of a nadir - at least in the sense of when the PSA might be expected to cross 4.0 and 2.0 and 0.4.

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T injected into thigh muscle, say, is slowly released. T can still be over 1,000 ng/dL 8 days later, as I discovered.

Transdermal patches (I used a daily 4mg patch for years) are a different matter.

In general, men (with native T) are advised to test T at the same time, since it does follow a circadian cycle. T tends to be highest around 7am & decreases throughout the day (I don't know by how much.)

-Patrick

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ah. I forgot about transdermal. I got shots in the stomach fat.

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Martin, using this half-life calculator calculator.net/half-life-ca... I came up with a T half-life for me of 7.2 days for thigh-injected testosterone cypionate. This was based on two lab samples, seven days apart.

At my TRT start (Sept 2017) I was injecting every 10 days, but the calculated T range over the 10 days was way too high (e.g., 2206 at start; 763 at end). And this drove DHT way too high, among other side effects. So I switch to two injections/week. Most recent T range (Apr 3-6): 725 high; 517 low. These are calculated numbers based on a single lab sample inserted into the calculator referenced above. You can only use the calculator if you first determine your doubling time using two lab samples where no exogenous T is added between the lab draws.

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Transdermal, whether a 4 mg patch or 4 mg gel rubbed on the chest, rapidly dissipates at 24 hrs. The half-life ranges from 10 minutes to 100 minutes.

GD

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Six years on ADT. Seems to have done a great job!

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My uneducated guess, more than likely the six months of early and aggressive chemo cocktail treatment in the trial with ADT the crutch starving reducing damaged cancer cells.

GD

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That is now standard treatment ( chemo + ADT) and the typical results are not like yours. So why your results are so much better is ... well its ok to speculate - speculation drives all trials, but I think it is too soon to say "more than likely".

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You are right that standard treatment seems to be Taxotere infusion every 21 days for 6 to 9 cycles and, maybe an oral, and ADT. However, this is a different treatment from what I underwent.

GD

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Gourd Dancer , In your trial with Dr A. How many Men went into complete remission like you did and how many progressed. Do You have a link to the study?

Thanks ,

Dan

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Dan, I don't know the up to date numbers. Here what I have:

"Forty-six patients were enrolled, and forty-five patients were evaluable. Median progression-free survival (PFS) was 23.4 months. Median overall survival (OS) was 53.7 months. Out of 45 patients with measurable disease, 22 patients had an objective response: 9 patients achieved a complete response; 2 patients achieved a partial response; 10 patients achieved stable disease. Frequent grade 3 adverse events included elevated ALT (17 %), hypokalemia (13 %), and hypophosphatemia (13 %). Grade 4 adverse events were rare and included low bicarbonate (2 %), hypokalemia (2 %), leukocytopenia (2 %), and neutropenia (2 %)."

I do not know what has been written to explain the variation other than Time from diagnosis to Time of treatment.

I know that he has treated well over 500 and was to publish. Cmdrdata may have an idea.

GD

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Thanks Gourd Dancer, The way I read those numbers 9 patients had a complete response out of 45,median overall survival 53 months , which is good. Progression free survival of 23.4 months ,I would say you are on the extended tail of the survival curve in this study, and that overall most did not have nearly as good of a response as you. I suggest these numbers may not be that different than the current early chmeo with adt.

Congratulations.

Dan

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It looks to me like the study is motivated by the interest in testosterone replacement therapy in older men in the general population. And this study seeks to extend that study to men "close to" healthy, aside from a weakened ability to synthesize testosterone, and who can "safely" be given testosterone. What I think is the maintream article on this topic is in the side bar, titled "eugonadal, untreated-hypogonadal and hypogonadal-men-receiving-testosterone-replacement-therapy" [ ncbi.nlm.nih.gov/pubmed/188... ] ; ie a group divided into // healthy // impaired-untreated // impaired-untreated//.

The two "prostate cancer" groups of active-surveillance and post-definitive-treatment would be classed as healthy v impaired based on T levels, and treated v untreated based on supplementation decisions.

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