What is Changing in Advanced Prostate Cancer?

[maley2711]

urotoday.com/journal/everyd...

Most here are probably aware of all th.is..but a nice short summary.

Isn't almost all metastatic PCa eventually castration resistant????

[Tall_Allen]

"Isn't almost all metastatic PCa eventually castration resistant????" Yes- that's just the natural history of prostate cancer. Why do you ask?

[maley2711 in reply to Tall_Allen]

I goofed!!! Actually, what I was wondering about was the differentiation between metastatic and non-metastatic castration- resistant PCa. In my simple mind, castration resistant refers to metastasis.....maybe an artificial distinction based on the limited ability of imaging to detect metastasized cancer? I would assume , that with improved imaging, more men will be told they have castration resistant metastasis, and fewer given hope that castration resistant "non'metastatic" gives them a much improved chance for better outcome? Now, I just read, that until very recently, there really wasn't any distinct different treatment for non-metastatic castration resistant ...which would make sense if in fact it is just a case of imaging having missed the metastasis. If in the lymph nodes, considered metastatic?

[Tall_Allen in reply to maley2711]

I very much agree that all castration-resistant men are metastatic, if only micrometastatic.

[maley2711 in reply to Tall_Allen]

OK...thanks for confirming!

[noahware in reply to maley2711]

That almost all metastatic PCa is eventually castration resistant is just the natural history of TREATED prostate cancer (via mainstream SOC), would be the more technically correct statement.

Early on, many decades before scans and PSA were readily used, castration was found to offer temporary relief to men with very late-stage advanced metastatic PC exactly BECAUSE most metastatic PCa is NOT castration resistant until a year or two after castration (or some medical treatment that approximates castration).

I, too, would assume that improved imaging would cause many more men to be told they have metastasis. It is partly the fact that this imaging is very costly and not commonly used on those earlier-stage, lower-risk men that there has not been a statistical leap in the recorded incidence of metastatic PC.

Care to guess how many men with "no known metastases" in fact have UNKNOWN metastases? It has to be a lot.

[timotur]

Very good article, thanks...! 👍

[maley2711 in reply to timotur]

glad someone liked it!! Heavy reading!!

[timotur in reply to maley2711]

Must read for us with Advanced PCa considering next steps.

[pjoshea13]

By definition, castrate-resistant [CR] PCa occurs only after castration therapy. There is no reason for PCa to select for CR cells if left untreated.

As I see it, there are two ways to delay CRPC:

1] delay ADT until palliation is needed and/or

2] use BAT (with ADT) to periodically reset the cells & delay adaptation.

-Patrick

[Ahk1 in reply to pjoshea13]

This is my struggle for a long time now “ when to start ADT”. My psa is up to 1.2 now and I am worried if I delay adt any longer, it might make the situation worse and cancer grows faster. Any ideas please?

[pjoshea13 in reply to Ahk1]

I fully understand what you are going through.

Back in 2004 Zytiga & Xtandi were a long way off. So, few options & Lupron, realistically, only good for two years. So I decided to put it off as long as possible. Fortunately, I also decided to boost testosterone [T] for as long as possible, & later, I alternated between T for 3 months & castrate for 3 months. More recently I am using a variation of BAT - I inject T once every 2 months & use oral DES to become castrate in between.

You say: "if I delay adt any longer, it might make the situation worse". Classic ADT as monotherapy will make the situation worse.

Some will counter that aggressive treatment now will delay the appearance of mets. It sounds very appealing, but I wonder what it means. With aggressive treatment, when mets appear the cells will be more advanced. We don't know yet how aggressive treatment affects survival. It might be a wash, in which case why suffer the morbidity of treatment? Or it could go either way. Then there is the question of months gained or lost. 3 months? A year? Probably not a year IMO.

Aggressive treatments are great if they are done with curative intent. But the drugs we have are good only for management of cancer. Nevertheless, many men think that palliative drugs might result in a cure. Aggressive treatments create aggressive cancer.

My own approach to managing the cancer has been to target subclinical inflammation, abnormal coagulation, etc, and to play the longevity odds with Metformin, statins, etc.

I wonder how many doctors have though deeply about this? You should try to find one & discuss it with him. I'm not a doc & can only point out the issues.

Best, -Patrick

[Hidden in reply to pjoshea13]

Patrick, This is an amazing analysis. As much as I appreciate the studies you post here, you are doing this community a disservice not offering your opinion as you did above. Nice job and hope to read more.