Dr. Leibowitz - Prostate Cancer Survivors and TRT

[gusgold]

Looks like about half had PSA progression but PSA declined after they quit TRT..so it might be worth a shot for QOL

Gus

ncbi.nlm.nih.gov/pubmed/199...

[pjoshea13]

Gus,

"PSA progression" is to be expected in hypogonadal men on ADT. It may be scary for some - Dr. Myers has talked about his own nervousness when using TRT on patients - but PSA activity is meaningless until it has settled down - i.e. when Morgentaler's saturation point has been reached.

The reason PSA declined after they quit TRT is that their T levels were low to begin with. They returned to a castrate or semi-castrate state. Starting out with low T on TRT has got to be stressful, since PSA will initially appear to be out of control.

Interesting that Dr. Bob goes beyond TRT in these cases:

"The target serum testosterone level was 1800–3000 ng/dL."

I have yet to understand why he aims so high. AR saturation occurs at a tenth of that range.

"The mean (range) serum testosterone level on TRT was 1391 (303–2637) ng/dL."

The mean was over 400 points less than the target minimum - with one guy, improbably, only geting to 303.

-Patrick

[Hidden]

Not just QOL.

I am confident that the idea is to delay the emergence of colonies of those prostate cells that can survive in lower T environment, by "feeding" the ones that can survive in higher T environment.

[Hidden in reply to Hidden]

You have, no doubt, seen this video on the giant pitri dish:

cnn.com/videos/health/2016/...

if you keep raising the antibiotic without killing all the batceria, the bacteria that remain will be those that are resistant to that level of antibiotic.

So with prostate cancer and T, if you lower the T, but do not kill all the prostate cells, those that remain will be able to survive in a low T environment. And if you do it again (enzalutimide), it will happen again. The problem with cancer is the calls reproduce without stopping by themselves, and now you can no longer stop them by reducing T. If you could encourage prostate cancer cells to live in a T rich environment, you could halt them by lowering T (which we can do.)

[Hidden in reply to Hidden]

A problem with this explanation is with the related idea of "velocity". Chemo kills cells that are dividing. So, it follows, that a cell (line) is more likely to be killed if it is dividing when the chemo is being given. That means that the cell (lines) with higher velocity are preferentially killed. This should result in lowering the velocity.

Yet we know that at end stage, the cancer often reproduces very rapidly. Hmmm.

[Daddyishealing in reply to Hidden]

So does chemo lower the velocity or are you saying that it becomes ineffective at some point for some men

[Hidden in reply to Daddyishealing]

I was speculating that both are true. 1: Chemo does become ineffective at a clinical level at some point, as do many other treatments for cancer. People die. And 2: upto a point, chemo should lower velocity, since chemo kills dividing cells. Cells that divide more frequently are more frequently vulnerable to being killed.

Yet last stage cancer is often high velocity: cells rapidly replicating, rather than just "not killed".

It could be that chemo stops killing dividing cells. I didn't think of that, but I think that that does happen.

But I was thinking that the reason could be that chemo treatments are often given every three weeks, so that cancer cells that divide every week could survive the selection pressure, with only one generation in three (say) being affected by the chemo.

[Hidden]

So this looks like a study of 96 men who received treatement of the prostate for their cancer, were not receiving ADT but still had low levels of testosterone. They received testosteront injections and 31 of them had no negative effects (cancer related) and presumably received the benefits of normal testosterone levels - mainly avoiding the problems of low testosterone levels.

For 31, the likely story is that the removal of the prostate got all the cancer, there were no metastatic cells to make PSA, so things went well and looked great (for 3 years).

For 9 more, they had a similar story but stopped the supplementation for other reasons. Not clear what those other reasons might have been. Not cancer.

For 56, who were called prostate cancer survivors, and so must have had definitive treatement of the prostate, either surgery or radiation, they all had PSA levels go up. They had some prostate cells that were alive, some of which may have been cancer, and possibly metastatic cancer. The 56 stopped the supplementation. For 33 the PSA went back down. For 23, it did not, and 7 of them got (new) mets.

Not a very adventurous study, yet 7 people (apparenty) developed new mets; that is, markedly worsened their condition.

7 larger mets vs. 66 lessened side effects vs. 23 higher PSA

[Hidden in reply to Hidden]

For the 56, the survivors (of definitive treatment), any remaining prostate cell is presumed cancerous; that is, presumed to have an increased reproduction rate. Apparently, after supplementation, 33 had a lowish reproduction rate and were sensitive to T levels, 23 a lowish rate and were not sensitive to T levels, and 7 were faster, possibly insensitive, and were located in a smaller met that grew into the observable size from the invisible or the ambiguous size.