Why Metastatic PC is Not Curable

[cesanon]

This was such a good answer by Tall_Allen, I thought it deserved its own post.

Most people have the wrong model of metastatic prostate cancer in their heads. They think of it as a weed that crops up: Keep after the weeds long enough and eventually no more weeds.

A more accurate metaphor is mushrooms growing at the base of an oak tree. The mycelium extends everywhere throughout the soil and into the roots of the tree. Occasionally, a mushroom crops up. You can pick all the mushrooms you want, but the fungus is never destroyed. There is no way to destroy the fungus short of destroying the roots of the oak tree and sterilizing the soil. This is what "systemic" means.

Can systemic treatment someday POTENTIALLY cure it? Maybe. Cancer, like HIV, hides in reservoirs. It is very hard to get to all the places it may be hiding. It evolves rapidly - any therapy-resistant cells eventually come to dominate. That means that there will always be some cells that don't rely on androgen-receptor activation, some that don't express PSA or PSMA, and some that aren't killed by microtubule stabilization (docetaxel). It also changes the microenvironment in the places where it nests so that they become more fertile for invasion. I'm talking about "cure" rather than "control."

I think that if we are ever going to control it, it will be through multimodal therapies (as for HIV) that attack it from several directions at once. So far, growth pathway inhibitors have been disappointing (the sheer number of growth pathways is daunting and increases as the cancer mutates), as have Immunotherapies - PC does not engender a big immune response and mimics "self" cells. Perhaps, a combination will be more effective - or maybe CAR-T. There is always hope.

Edit:

Real nice post with a lot more detail on this subject:

pcnrv.blogspot.com/2017/05/...

[Hidden]

Thanks for cheering everyone up. I think I will go watch the cartoon channel.

[cesanon in reply to Hidden]

I don't think this is so bad.

I was always looking over my shoulder and wondering about this issue.

What tall Allen says makes sense. It gives me a better perspective from which to manage the disease.

[j-o-h-n in reply to Hidden]

Cartoon channel. I'm sorry but I couldn't stop giggling at that idea... my original post when I read TallunderscoreAllen's post was "Shit... you just ruined my day".

Good Luck and Good Health.

j-o-h-n Saturday 08/04/2018 12:23 PM EDT

[Hidden in reply to j-o-h-n]

Whoa baby!

[Hidden in reply to Hidden]

Make my day! Hahahaha

[Ralph1966 in reply to j-o-h-n]

"Shit...(TA) you just ruined my day" ? LOL

AS USUAL

You forgot the Good Humor at th end...

[Canoehead]

elsevier.com/about/press-re...

Dr. Scher’s work suggests you may be wrong. I choose to believe you are wrong.

There is insufficient evidence now. Your point makes sense and is the conventional wisdom. But killing as many cancer cells as possible, debulking a tumor, etc. seems to result in a “cure” or something close to it for some men.

BCBS just denied coverage for my radiation treatment, which hopes to replicate Dr. Scher’s results. Said it was NMN (not medically necessary). I’m surprised at your post, because I thought the only remaining “incurable” devotees either worked for insurance companies or were in arrears on their mandatory continuing medical education hours.

[cesanon in reply to Canoehead]

The article you cited restates exactly my understanding of what tall Allen said:

"In the past, all forms of metastatic prostate cancer have been considered incurable. In recent years, the FDA has approved six drugs for men with metastatic disease, all of which can increase survival. In a study published in Urology®, researchers demonstrate for the first time that an aggressive combination of systemic therapy (drug treatment) with local therapy (surgery and radiation) directed at both the primary tumor and metastasis can eliminate all detectable disease in selected patients with metastatic prostate cancer."

Well maybe it is a tinge more optimistic. But I read it the same.

[Tall_Allen in reply to Canoehead]

There is no question that local therapy decreases PSA and early metastases are slow to occur anyway. What his pilot study lacks is a control group that would tell us what would have happened if those men had not received the treatment. Survival is the only useful endpoint, because any endpoint that depends on PSA or detectable metastases is a self-fulfilling prophesy. This is what I explained here:

pcnrv.blogspot.com/2017/05/...

[cesanon in reply to Tall_Allen]

Tall-Allen

1. Real Nice article here:

pcnrv.blogspot.com/2017/05/...

2. "Until we have some proof, patients should approach metastatic treatment for anything but palliative purposes with caution."

So if you have had radiation treatment of several oligometastatic sites, what is a reasonable post metastasis "watchful waiting" protocol.

It seems like zapping metastasis with radiation may interfere with your ability to track it with PSA or PSMA imaging (or even c11 choline or acetate imaging?)

[Tall_Allen in reply to cesanon]

That's a very good question - how do you track the micrometastatic progression? I think that most of the traditional biomarkers (PSA, bone alkaline phosphatase) would be lower after gross metastasis-directed therapy. I wonder if CTC is more or less useful - I haven't seen any studies on it. There is a limit to what can safely be zapped.

[cesanon in reply to Tall_Allen]

What is CTC?

[Tall_Allen in reply to cesanon]

Circulating Tumor Cells (e.g., Cellsearch). Any count ≥5/7.5 ml of peripheral blood is indicative of systemic cancer. Lately, they have been analyzing the tumor cells too for certain biomarkers (e.g., PSA, PSMA, AR-V7)

[auroracham]

Actually, MD Anderson believes they will reverse my cancer and make the DNA in the BRCA gene fight cancer instead of build cancer. We shall see if they are right as I am now one of their guinea pigs. Wish them and me luck.

[cesanon in reply to auroracham]

Would that mean it only will work for those with BRCA genes?

[Tall_Allen in reply to cesanon]

Those with germline repair defects may benefit from treatment with PARP inhibitors or platins:

pcnrv.blogspot.com/2018/02/...

(note list of clinical trials)

Those with a rare condition called MSI-hi/dMMR for which Keytruda is FDA-approved for ANY cancer:

keytruda.com/hcp/msi-h/abou...

[j-o-h-n in reply to auroracham]

A gigantic

G O O D L U C K and Good Health.

j-o-h-n Saturday 08/04/2018 12:27 PM EDT

[flyguy in reply to auroracham]

Who have you seen at MD Anderson? I've been there and find that they tend to be regular SOC (standard of care) practitioners.

[cesanon in reply to flyguy]

Dr. Myers once made a comment to me about why he set up his own practice.

He said that major medical centers institutionally have to use Standard of Care protocols. It is not an option for them to run such large institutions any other way.

I think that institutions like MD Anderson operate on the cutting edge of Standard of Care protocols, but they are still constrained by them.

I had another Dr., who shared a number of patients with Myers, sort of shrug his shoulders in amazement at Myers protocols, then comment that there had to be something to what Myers was doing as Sloan Kettering seemed to be following behind him adopting his protocols, with a five-year delay or so.

[auroracham in reply to flyguy]

I first saw:

Sumit K Subudhi | MD Anderson Cancer Center

faculty.mdanderson.org/prof...

Sumit K Subudhi, MD, PhD, Department of Genitourinary Medical Oncology, Division of Cancer Medicine

I visited twice with him, talking about my options, and about down the road options. Now, that my Zytiga stopped working, he referred me to this other researcher/ doctor for the clinical trial:

Timothy Yap | MD Anderson Cancer Center

faculty.mdanderson.org/prof...

Dr. Timothy Yap is a Medical Oncologist and Physician-Scientist based at the University of Texas MD Anderson Cancer Center. He is an Associate Professor in ...

Dr Yap does research Monday, Tuesday, Thursday, and Friday. He only sees patients on Wednesdays. He is my clinical trial doctor.

[StayingOptimistic in reply to auroracham]

Any success with MD Anderson?

[MelaniePaul]

I totally agree. That is a wonderful explanation.

[Dayatatime]

The problem with randomized trials and pilot studies is not one man entered in them are of the same makeup. There will never be enough men of the same type to put in a trial to know what exactly will nail this thing down. This disease has been treated basically the same since the forties and it seems to be ingrained in everyone's head that it's palliative care until all options are exhausted. Even a lot of the current data today is taken from patients that never recieved anything more the the standard of care. Of course it's only going to reflect exactly what that treatment results in. Over the last 70 years advanced prostate cancer has been termed incurable. To me it's the same as constantly telling someone they are ugly, eventually they start to believe it.

When first diagnosed I read about some of the radical options bigger hospitals were doing with some great results. There is some great stuff published in European Urology and pubmed on treatments outside of the normal. I would often print these and show them or tell my first Oncologist about them and she would always say "but nothing is proven." I cannot begin to tell you how frustrating that got. I talked to 4 other doctors with the same attitude. Then I found one that said we are going take a chance and made no promises. Bottom line is he gave me that chance. If your going to get ahead of this disease today and now "proven" is not going to get you there. No argument proven will extend your life but that's it.

Early aggressive multimodal treatment is what is needed. It will work for some and not for others. There will never be enough men with the same genetic makeup, age, specific cancer and same treatment histories to show anything is proven. You need to give yourself the best chance by finding a doctor and hospital that will use unconventional therapy. It would be very interesting to know the amount of men that could have been potentially cured if they had doctors that were aggressive and didn't only go with the proven theory of treatment options.

Ron

[cesanon in reply to Dayatatime]

"Then I found one that said we are going take a chance and made no promises. Bottom line is he gave me that chance." Dayatatime

May I ask who is the Doc you found and what was the treatment?

[Dayatatime in reply to cesanon]

Dr Jeffrey Karnes at The Mayo Clinic in MN offered me surgery with an extended lymphadenectomy removing 42 lymph nodes. Diagnosed February 2016 at 46 years old, PSA at 286 with bulky disease in pelvic and abdominal nodes. HT up front, Chemo shortly after bringing PSA down to 1.8. Added Casodex again brought it down to .51 then open prostatectomy performed in December 2016 have had <0.01 PSA and clean scans since. Did adjuvant HT and last shot was February. Time will tell for longevity but no matter what I am convinced along with my medical team that without the surgery I would not be where I am at currently.

[jimk_mb in reply to Dayatatime]

Question to Dayatatime. Did you have any lasting side effects from the extensive removal of lymph nodes (e.g. lymphdema)? My reason for asking is that I had several LNs removed in 2012 as part of my prostatectomy and am now considering surgery to remove others based on results from Ga-68 scan. Thanks.

[Dayatatime in reply to jimk_mb]

So far no bad side effects with lymph nodes. I do drink a lot of water and never add salt to anything because I did read that will aid in preventing lymphedema. No urinary incontinence issues either. I do have ED and not going to lie, I do miss having the ol boy function as he used to. Nerve sparing was done on one side but so far not so good in that department. We have a stage IV cancer and the way I look at it is there is no way to get out of it without scarring of some kind. It's a battle wound.

[jimk_mb in reply to Dayatatime]

Info is much appreciated, thanks. Trying to make a decision as to 1) lymphadenectomy, 2) radiation or 3) do nothing and rescan later. Take care.

[StayingOptimistic in reply to jimk_mb]

Jim, what was your decision please? I am going to be in the same Situation soon.

Thank you

[jimk_mb in reply to StayingOptimistic]

I decided to go with radiation, which is now in progress. The reason for my decision is that I talked to 3 individuals that had the surgery to remove LNs based on the Ga-68 scan and they didn't get much of a durable response. My surgeon proposed just going after the 1 LN that showed metabolic uptake on the scan. Probably would leave micro-mets that don't get picked up on the scan.

So that left radiation as I did want to do something. Radiation oncologist opinions varied as to whether I should do SBRT to suspect LN only or IMRT to a broader field. The size and area of the broader field varied depending on who I talked to. No easy answers here.

I ended up going with my MO's recommendation which was to radiate a segment of the left iliac LN chain surrounding the suspect LN. I have no idea what the correct approach is, but this made sense to me and I am comfortable with it. Also, the MO has me on what he terms hormone therapy light which is anti-androgen mono-therapy (150 mg/day of bicalutamide.) No side effects so far. Also, I preceded all this with surface radiation to my breasts to prevent breast growth on the bicalutamide. And I thought retirement would just be fly fishing and other fun things.

Hope this helps and feel free to ask if you have any more questions.

[StayingOptimistic in reply to jimk_mb]

Thank you very much Jim. You am going to digest this info and get back to you

Thanks again

[StayingOptimistic in reply to jimk_mb]

Good morning, Jim

How are things going with you?

[jimk_mb in reply to StayingOptimistic]

Feeling good. Finished radiation to left pelvic lymph nodes about 2 weeks ago. Moving forward. Take care.

[YYJguy in reply to jimk_mb]

I am doing this same protocol for my lymph node metastasis.20 rounds EBRT radiation, and the same Bical on this now 16 months. MO recommends 2 yrs then coming off. Or maybe I will pulse it after that and do intermittently.

How did things work out for you?

[jimk_mb in reply to YYJguy]

In my most recent PSMA (July 2022) scan no cancer showed up in the lymph nodes.

However, it did show some cancer in the prostate bed. So I had 5 sessions of SBRT in Sep 2023 for that at UCLA. My PSA has gone to undetectable (<0.05) since April 2023. Fingers crossed. Best wishes YYJguy..

[cesanon in reply to StayingOptimistic]

Previously, tall Allen has made a compelling case, citing clinical studies, that once the cancer goes metastatic localized treatment such as radiation and surgery.

Now, if you have a tumor near a vertibrae, that's an exception. But basically it is in most cases wasted sword motion.

[Grumpyswife in reply to Dayatatime]

Thanks for not lying. I spoke to at least 5 men (with prior authorization) before my husband’s nerve sparing laparoscopic RP and they told me they were functioning perfectly. They were not as honest as you, I think.

[cesanon in reply to Grumpyswife]

Men exaggerating their sexual capabilities. LOL

[Ralph1966 in reply to Dayatatime]

Hi. How often you repeat the full body PET scan? Do we have to repeat the PET scan if the PSA is undetectable?

[cesanon in reply to Ralph1966]

There are some types of prostate that can't be tracked with PSA tests.

[Lombardi24]

So...basically the current treatment I am on (lynparza) is killing the mushrooms...but not the fungus (stem cells?) that remain impervious to treatment. Seems as though the only way to ever 'cure' it would be by getting the immune system to recognize all the types of PC cells and irradicating them. The prognosis doesn't sound very hopeful.

[cesanon in reply to Lombardi24]

"Seems as though the only way to ever 'cure' it would be by getting the immune system to recognize all the types of PC cells and irradicating them."

Seems like there is a lot of immune system work going on.

[Tall_Allen in reply to Lombardi24]

PARP inhibitors work great in the men in whom they work, albeit with lots of adverse effects. But I don't think anyone thinks they are curative - they may add to survival, though.

[Magnus1964]

There should be some corrective thinking here. If Pca is detected early enough there is a real chance of permanent remission with surgery, chemo, or radiation. Beyond that those of us who have metastatic Pca, i.e. stage 4, The best we can do is fight with ADT and other new developments. And there are a lot of new things coming down the road. After 26 years of fighting this disease the best I can do is to do all can with a healthy life style and I do take and have taken many non standard supplements. Read all you can and do your own research. Good hunting and good luck.

[cesanon]

HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR, HAR,

[Rmanns]

Good analogy.

[duckman52]

You guys are to funny, it makes me smile. I have been trying to figure out a game plan, and at this point I am not totally certain, but believe it may be the best approach for me. I am 61, in 1997 I was diagnosed with hepatitis c, I was 40 years old. Over a period of 17 years we tried to get rid of it. Interferon with peg one year 48 weeks, 2nd go raised the dose of interferon and no luck, tried one more time where it was 40x and still no luck. At the age of 57 years old Harvoni became available and out of nowhere a new doctor I saw asked if I wanted to try it and I said yes at no cost to me, would have been @ 250,000.00. After 20 some weeks they did a blood test and finally it was gone. I believed that I would die from hep c and liver failure. Now I have prostate cancer with lymph nodes involved. I have read a considerable amount and listened to what you people discuss and all the different treatments at our disposal and think maybe the best way to approach it for me is to do as little as possible but enough to get by for another 10 years if possible. I still do not have a clear picture of time frame of morbidity, gleason 9 , all 12 on biopsy cores taken, perennial invasion and after RP local lymph nodes, diagnosed 4-2018. After a while a person gets tired of trying to always get an angle. At this point today I am healthy, strong with a reasonably good attitude and would like to go as long as possible but I don't think I am willing t let these treatments change who or what I am any more, I don't like it. Just do enough to get by until they have a cure if and when I last that long. Still wish I knew how long that might be.

[StayingOptimistic in reply to duckman52]

Very nice outlook on this. I wanted to think like yours. I do it for a minute and then spend 9 minutes trying to figure out what is the best approach to take. It’s is so difficult for me