It is time to set things straight in regards to the oligometastatic state in prostate caner. Posters will tell you that it does not exist because of micrometastases. So let's take a look at micrometastases first.
The dreaded micrometastases.....the ultimate death sentence... they grow into big tumors...we are doomed...or are we?? To understand minimal residual disease after primary treatment in prostate cancer-I have chosen this article:
In reading the article, you will note that all circulating tumor cells are not created equal--
Active dissemination of tumor cells requires specific phenotypic characteristics which confer the ability to the tumor cell to detach from the surrounding cells, survive free of them, migrate towards the blood vessels where they cross the capillary endothelial wall to enter the circulation.
Then-there is survival in the circulation-from the article:
In order to implant at distant sites, CPCs must survive in the circulation, it has been suggested that only 0. 01% of CTCs can produce a single bony metastasis [53, 54], and injected CPCs obtained from men with castrate resistant prostate cancer may fail to produce metastasis when injected in immune compromised mice [55].
If only 0.01% of CTC's have the ability to produce an actual metastasis, then the threat is there, but is it something to lose sleep over?? Just remember that the 0.01% that can form a met, still needs to get through the circulation (macrophages, T cells, etc...) find a niche that they can actually grow in (adequate circulation and appropriate substrate) before becoming a possible met..
From the article:
It has been shown that ADT can eliminate bone marrow micrometastasis in approximately 80% of patients [173, 174].
So, when undergoing treatment, patients are attacking micrometastases and eliminating them...
It is why there is an oligometastatic state. This minimal residual disease is not close to forming a met for the most part... (99.99%), and thus, does not bear an accounting for in the minds of MO's.
Circulating tumor cells can be found years later after treatment in cancer patients that have no evidence of disease... Ask your local expert to explain that fact?? The answer-no one can...or....the simple version--they just don't metastasize...
Thus, we focus on the number of tumors that can be defined as oligometastatic for the purpose of treatment and reducing tumor mutational burden... Upon completion of SABR COMET 10, we may finally have an answer as to what is the number of tumors that define the oligometastatic state...
As always, I welcome discussion... ( I am on the road, so patience may be needed for a response)...
The Science is Coming !!! and it gives us... HOPE !!!
Don Pescado
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NPfisherman
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Thank you for posting this interesting article. Coincidentally or not it is a topic that has been discussed recently on our APC forum.
And you're write-up is great and helpful. The article itself is intriguing and discusses important topics that I haven't seen explored in the same way before.
I believe the topic is timely because the success of therapy such as triplet therapy are extending that period between diagnosis and initial treatment and later progression and resistance. It would be great to understand in particular this whole micrometastasis business.
So I looked up the publisher of this journal and it seems to be okay, in other words not a predatory publisher.
I hope the post gives everyone further insight into micrometastasis....how many steps it takes to get there from a CTC to a micromet.. etc.. and the risk.... for the BAT guys, they are dealing with micromets during ADT treatment phase...
Appreciate your noting the age of article and publisher status... I hope you are doing that everywhere, because.. can you believe ??.... it's been a while, but I saw somewhere a poster defending using continuous ADT over IADT and using this article :
An 11 year old article, and there was not one word said in regards to that study's age or the PSA number when treatment began, etc... Can you believe that not one person said a word ??
I guess they didn't feel comfortable discussing it with the poster... In comparison, I guess you must feel comfortable discussing things here, and that is our goal at FPC.....
ADT eliminating micrometastases is a good thing, correct? Is the risk during the supraphysiologic testosterone phase and if so what is the risk exactly?
Even my great detractors know that the elimination of micrometastases is always a good thing...
I did notice that--
You are a new member at FPC (The Twilight Zone), and your profile has some nuggets of information:
I am an oligo-recurrent bone metastatic prostate cancer patient. Updated 3/2024
Currently, just approaching a "2nd BCR" and have no idea if my projected new PSAdt will still be 5 months, more, or less?
I suppose my next step is to get another PSMA PET/CT.
**Welcome to the forum and thanks for replying... Sorry to hear about the recurrence (Yeah, it sucks !!!), but we have a number of oligo-recurrent guys here, including me. You are here to look at options and additional information, and we get it...Most people share their advice/strategies openly here, and if that is why you are here, then hopefully, you will get some information. Also, thanks for being in clinical trials--it is how we will get there...
DD
And about that second question... more to follow...
The risk is during the supraphysiological testosterone phase, but what is the risk exactly vs the rewards, and is their a rationale for doing it?? see below:
The reward of DNA breakage and apoptosis must be measured against the risk from the Super T phase, and that is unknown. As we gain knowledge about biomarkers, they will be able to see who is an appropriate candidate, and who is not.
If you are contemplating BAT in treating your recurrence, there are many posters on here that are better qualified/ more knowledgeable than I am about BAT... MateoBeach comes to mind, and here is an article by pca2004 (a poster of over a 1,000 posts, but deemed unfit to post any longer for no clear reason):
Taking a break on the drive.. Hope you are still vacationing...
Indeed... glad you approved... many people likely believe that all CTCs are turning into micrometastasis... only very, very few..... it is called minimal residual disease for a reason...
Until micrometastasis can be detected, there is little to do .... I do wonder how the RAVENS trial will go using RA-223 and SBRT for oligometastatic bone disease in PCa, and dealing with micrometastasis.
Yes I think Nal certainly and Patrick possibly also thought that you might be able to discourage CTCs from docking together by taking Natto. I also take a baby aspirin every 3 days. Also I wonder whether strengthening the bones through exercise and taking K2 might discourage docking. My PSA is beginning to go up. I reckon I will end up with a scan in 3 months time and will then hopefully see part of what we are dealing with. Can’t really complain as CyberKnife and 6 months bicalutamide may well have bought me 2.5 to 3 years without treatment. Dave I hope you are enjoying your holiday. 👍
I am enjoying my holiday...Thanks....You got good mileage out of cyberknife and 6 months of bicalutamide ...almost 3 years...how sweet it is !!!It is a shame that Patrick can no longer post... hope he is doing well...
The usual trigger, I become detectable on the USPSA. It is then that the synchronization of treatment begins to develop...monitoring... waiting for the PSA to get to a level for the Pylarify scan..Then, starting lupron/ eligard prior to SBRT to elevate T... finally, starting abi after SBRT...
Glad to hear it Dave. Well you have certainly kicked off an interesting thread during your holiday. Yes a great pity that Patrick can’t post. If he is reading this I send him my best wishes.
No...he can not post or reply ...I guess prostate cancer patients have to be silent on a prostate cancer forum. The people doing the silencing.... People that do not have prostate cancer...two tiered justice..
Very interesting me Old M8, but the paper is 2018. Have you found any updates as this is a topic very close to my heart.... I had recent cryo on one side 5 years after hifu on the other side. I'm blowing hot n cold 🫣
Good to hear from you. My daughter is absolutely amazing. At almost 8 years old she apparently knows much more than I do about, well, Everything.... The hifu to the left side was a completed success, then the right side showed a small lesion which I had frozen. The cryo had a shorter recovery time, but I had no additional treatment, no anti androgens or immuno. I'm due my first PSA which will reveal... Something 🤔All the best to you and yours
Thanks for the article and post NPfisherman. I'll copy paste here the reply I had put in another post that was about "oligometastatic state" in order to explain why I think that the approach suggested by Dr Scholz seems logical and safe to me.
What I like about the approach proposed by Dr Scholz is that it is methodical and can help going through diagnostic/treatment in sequential order instead of immediately jumping to the worst conclusion.
I'll take my own situation as an example since it is pretty much what he's discussed in many of his videos.
A patient with cancer limited to the prostate area and pelvic lymph nodes goes through a treatment with curative intent (Lupron + Abiraterone + radiation in my case).
Once the curative intent treatment is over, we wait to see if Testosterone comes back and whether the PSA stabilizes after a few months or keeps going up.
My PSA went up every blood test and was now at 1.07 mid-May. We did a CT scan that showed nothing and a bone scan that showed a single met on the right shoulder blade.
What Dr. Scholz suggests doing in this situation is that rather than immediately electing to put the patient on ADT for life, perhaps needlessly, perhaps not, is to approach this by a process of elimination.
Step 1: You only ZAP the lone metastasis that has been discovered without giving ADT right away so that the ADT is not masking other potential areas of tumor growth.
Step 2: After the radiation, you monitor the PSA closely to see if it is now stable or if it is still rising.
Step 3a: If the PSA is still rising and a new scan reveals a meta that was missed on the previous scan, then you treat it locally and ZAP it and repeat step 2.
or
Step 3b: If the PSA is still rising and a new scan shows nothing new, then you treat it as a systematic issue and you take ADT until it becomes undetectable and then you stay on it two more months for good measure. Then you take a vacation and see if it is stable or rises and act accordingly.
or
Step 3c: If the PSA is now stable, then you assume that your initial curative intent treatment got rid of your systematic cancer burden aside of a metastasis that was initially missing during the original treatment because it was too small and away from the pelvic region treated. But now that it has been treated, you have a chance to be fine as your cancer load/burden is gone or small enough that your immune system can deal with it.
By approaching the issue procedurally like described above, I do not see why we'd be more at risk since all of this can be assessed in a relatively short time.
In my eyes, I do not see an immediate danger with this approach. And I do see a possible benefit because if you are lucky enough to fall into step 3c, then you won't shorten your life by taking ADT that you might not have needed. You only take ADT because you've confirmed that you need it.
Dr Scholz is an MD that is usually ahead of the trend. He is basing his approach off the Phase2 trial-EXTEND in using SBRT with IADT and applying "the art of medicine" in detailing limits to treatment. While I have never seen trials using meds to get to an "undetectable" PSA (Is that an uspsa?) ,and then stopping 2 months later, this does not make it wrong... once again, medicine is not just science... there is decision making involved based off the disease course and presentation.These kind of things are lost to non-clinicians that think in terms of rigid SOC ...They can see the Science, but lack the clinical experience to see the art...
My MO at Cleveland Clinic treated me for 22 months after SBRT ( He wanted 24 months, but I wanted some hope for testosterone). Why?? Because doing SBRT to my one met essentially put me as a BCR- no metastasis from his point of view... thus 24 months. This time, he treated me for only 12 months post SBRT...again....one met... Show me that treatment regimen in a study...you can't... it doesn't exist...Do I think he is wrong??? No....He has significant experience with a number of patients like me that he is treating using IADT with SBRT...
You will hear people say that SBRT is "whack a mole" and is treating PSA, not the cancer, but ask yourself if removing tens or hundreds of millions of cancer cells and decreasing tumor burden and mutation burden is not treating your cancer and slowing the progress of disease... Anyone that says otherwise is fooling themselves.
Have trials using SBRT been on the rise or on the decline?? That should tell you where the Science is leading us...
Good topic, NP. We all produce cancer cells (in addition to PCa) every single day, yet those cancerous cells never go on to produce a tumor - for all the reasons outlined in your post.
In the recent PeterMac GU podcast with Dr. Alicia Morgans (Dana Farber), it was evident that Declan was very supportive of TRT for people coming off ADT, esp. iADT. (Dr. Morgans was more restrained in her endorsement). As mentioned in the podcast, it is one of the reasons Relugolix is preferred for ADT (cost not being a factor), as T rebounds much more quickly. Dr. Morgans also points out that the recovery of T will unmask residual disease, so it may in fact be beneficial in identifying potential sites for SBRT treatment. (The italic portion are my words, not her's)
I thought the video Marnie put up was spot on...A true testament to where we are going in treating PCa... Forward thinking... and that is what we need..
Great post Mascouche. You describe my situation right now; oligometastatic, 3 months post 30 months of ADT same drugs as you. currently PSA undetectable, Testosterone <7 MO and RO gave me a 40% chance of "cure" ie: cancer will not return for 5 years
". . . then you won't shorten your life by taking ADT that you might not have needed. You only take ADT because you've confirmed that you need it."
As I have commented several times previously, the continuous use of ADT in general - without "testing" for durable response - seems a crude application of a potentially effective treatment when used "as needed". Continuous use will usually guarantee an eventual CR-status. The people at Peter Mac seem to "get" this, as they are embracing the notion of deescalation of treatment when appropriate - which potentially preserves treatment efficacy and improves QOL.
cujoe quoted -- " .... then you won't shorten your life by taking ADT that you might not have needed. You only take ADT because you've confirmed that you need it."
cujoe wrote -- " As I have commented several times previously, the continuous use of ADT in general - without "testing" for durable response - seems a crude application of a potentially effective treatment when used "as needed". Continuous use will usually guarantee an eventual CR-status... .. "
My Orchiectomy is a forever ADT but interestingly Dr. Onik prescribed Cypionate (Testosterone) injections that I've been able to cycle on-off-on-off.... as per PSA results along with PSMA PET/CT and AXUMIN scans since 2016. Thinking that maybe keeping PCa buggers confused with T-use and Dr. O's injection of Opdivo+Keytruda+Yervoy that he gave me in 2015 has so far prevented my 5+5 popping up after 9 years.
Quite the result for a G10... You are a glorified BAT project using T with the orchiectomy... Congratulations...🎊A successful example of the Dr Onik approach...
Thanks and on a MSC Yacht Club Cruise RIGHT NOW totally blasted after knocking off a 750ml bottle of Organic Red and a Chef's prepared special Curry Dinner
a2c - Those who believe that Adaptive Theory has merit would probably say you are doing just what you should be doing - to keep "the PCa buggers confused". Out of curiosity, how high do you let your T go - and for about what sort of interval.
And that's why you should watch the last segment of this PeterMac GU podcast with Dr. Alicia Morgans for that reason. Start around the 27:30 min point:
After injection T goes only to 1600ng/dL then stabilizes to 500+/- and then another injection. Recently PSA went to 6 or 12 if not on Dutasteride so stopped after PSMA positive with Biopsy showing 3 @ 3+3 and now T<2.5 with PSA @ 0.1 so AS for now.
1600ng/dL after injection down to 450+ before next and cycling back up like a roller coaster but not back down to castrate level like typical BAT unless PSA jumps up. That's the difference in what I'm experimenting with compared to the more standard protocol.
As I type, I'm on a no *T* 'cause testing showed PSA>6 or double since on Dutasteride and PSMA PET/CT positive in 3 spots in left prostate that biopsied at 3+3 with now after a couple of months off off *T* my PSA is .1 and *T* is approaching 2.5ng/dL Thinking I'm STILL Hormone sensitive and yet with basically NO *T* I'm feeling great.
Buzzzzz is strange, NOT A TYPICAL EVENT 😅, but will live with it until sleepy time 'cause it's better than being horizontal on a COLD SLAB IN A MORGUE.
In the GU podcast linked in the reply to 6357axbz above, Dr. Morgans says the T rise serves to "unmask" PCa, so your cycling should be doing some of that; i.e., thus, the PSA rise. Moffitt did a small PCa adaptive trial where they treated for a 50 % PSA drop, then stopped and waited for it to double back to the baseline, Rinse and repeat. Their results using that protocol were pretty impressive. Seems you are doing something similar - sans the current wine buzz. Day at a time. Party on! But maybe no cycling for the rest of today. Curry and wine = curcumin + resveratrol. Functional food X 2. Cruise On, Brother!
Can't bicycle unless in the gym so no Wild Hogs or Cars to worry about. Planning on a Walking on Water work out about 3am on the decks as we head for Nassau in the AM.
Right now on aft of ship waiting for SpaceX launch that might be seen as it passes by. Wife is holding on to me so I don't go OVERBOARD like Goldie Hawn
I saw a SpaceX launch a year or so back. It was pretty spectacular to see the booster stage drop-off. Remember: Safety harness + life jacket along with the wife and alcohol for buoyancy and EPIRB so you can be found if you do a Goldie dive.
NOT that I overdo things, 😜, but my younger brother is now recovering from a triple bypass today. I had a JW Blue for good luck before he went in and NOW I'm sipping some Don Julio Blanco Tequila as he is coming out of anesthesia.
I lost my Big Brother to pancreatic cancer about 10 years ago. Hardly a day goes by that I am not reminded of him in some way. Older brothers are very special and you are obviously on-board with the "brother program". Cherish every moment you two get to share. Nothing says it much better than this:
Sorry to hear you are in such a state...From my reading, I believe that I recall that ductal and intraductal may not do well with radiation. Overall, I believe that MSK is a solid institution. While you are not MSI High, I believe that Keytruda may provide you with some benefit with your multiple mutations.
Thanks for a great post that fits my current situation( oligometastatic, 3 months post 30 months of ADT ) , my plan is to stay on my "vacation" until PSA rises and then use SBRT if needed + Estrogen therapy instead of Lupron.
Should we use HU support, or post our requests on the ,"This site is unmoderated " location... They do not erase that one...leaving the requests up...forever... what were all of Patrick 's poster names??
Sent a message to HU... they turned off the ability to post or reply on the MaddieHU site... and I will get a response in a few hours... let you know...
For those that chose to debate and lock horns with him:
1)Nalakrats--- gone from HU... period
2) Patrick-- can not post or reply on either site..
3) Me-- I can not post or reply on APC, and can not message others unless I am messaged first
4) Cujoe-- similar to me... his big crime was asking for an apology for another poster that was insulted by that individual...
5) Other names that I do not recall...
We did not arrive here by chance... it was the only PCa forum left that was not under Malecare control.
Our interactions occured while on my initial ADT therapy...when I was a hormonal desert and had quite a bit of emotional lability . I drove friends away, which I was able to recover later, but I do have some regrets.
Sometimes, I may post to prevent what I term disinformation in regards to cutting edge issues like IADT, Micrometastasis, or SBRT for example. I am someone that has my eyes focused on the coming advances, and how to incorporate them into treatment.
He is someone with his eyes focused on strict SOC... Only a Phase 3 or 4 is truth..For some newbies, he is a godsend and deserving of praise.
I have been a clinician, and he has been a researcher/ patient advocate...
Do we see all things the same?? Hardly, but there is room (at least for now) for both..
Of the two of us, it will be me that is eliminated in the end most likely... Fighting the Power may seem like the thing to do, but the odds are not in your favor...
Some friendly advice that you may or may not utilize...
Good advice but I had to respond to his characterization of a respected urologist's well intentioned videos as 'internet garbage'. Wondering why we have to walk on egg shells when this arrogant know-it-all takes over the forum as he has done. I know I am walking a fine line here but why does the moderator cut him so much slack? I hear you, but I couldn't resist indulging in a little debate action. He actually succeeded in making me quit HU. I am back under a different name. The game remains the same. Nothing has changed. Thanks for pointing out the awesome contributors that this loose cannon has managed to chase away. Patrick was my favorite with Nal a close second. It was a sad day when TA showed up. Strange how so many idolize this guy.
There is a Youtube video containing a round table with Dr Efstathiou and 3 European urologists. Close to the end of it a German professor shares the following: Among the patients I see at my surgery, half of them just want me to tell them what they have to do. They don't want to know any details about their disease, treatments,etc, their attitude can be summarised as: "Tell me doctor what I will have to do and I will do it". The 45% of the other half come prepared, ask questions and engage into all sorts of conversations. Finally, there is this 5% than I can learn from them!
TA is perfectly suited for the first 50% group and acceptably so for the second 45%. He is an average doc's proxy, free of charge, available online 24/7, has a wide gamut and a very fast turn over. What else can someone desire of?
Each individual brings what they have to the table... Emotions, personal and professional issues, faith and beliefs, a lifetime of ups and downs... etc...
How we choose to interact with others is a whole different ball game...
In the end, we are all dust, so let's all try to get along.... 😂
Doc Pablo - the man I seem to remember once referred to as The Mule. Damn fine to see you feeling well enough to read and express your fine sense of humor. I'm guessing the humor part is what you need in spades right now.
I usually read (or rather re-read) Ryan Holiday's 2016 book, The Daily Stoic, most mornings as I start my day. Today, the June 04th entry made me think of you:
* * *
June 4th
THIS IS WHAT WE’RE HERE FOR
“Why then are we offended? Why do we complain? This is what we’re here for.”
—SENECA, ON PROVIDENCE, 5.7b–8
No one said life was easy. No one said it would be fair.
Don’t forget, though, that you come from a long, unbroken line of ancestors who survived unimaginable adversity, difficulty, and struggle. It’s their genes and their blood that run through your body right now. Without them, you wouldn’t be here.
You’re an heir to an impressive tradition—and as their viable offspring, you’re capable of what they are capable of. You’re meant for this. Bred for it.
Just something to keep in mind if things get tough.
***
Your "toughness" has never been in doubt. Keep getting better, Mon Ami.
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