I think it is relevant to some here
MDT and Intermittent ADT for Oligomet... - Advanced Prostate...
MDT and Intermittent ADT for Oligometastatic PCa
Written by
Scout4answers
To view profiles and participate in discussions please or .
Read more about...
74 Replies
•
Metastasis-directed therapy (MDT)—or local therapy intended to eradicate individual metastatic lesions—extends the principle that local therapy can be curative for localised cancers to patients with metastatic disease.
"Dr. Tang concluded his presentation with the following take home messages:
MDT combined with HT as part of an intermittent regime improves PFS and thus time off hormone therapy
Subgroup analysis, although limited, demonstrate a persistent effect across important subgroups
MDT combined with hormone therapy as part of an intermittent regimen improves eugonadal progression-free survival
Intermittent hormone therapy in combination with MDT may facilitate prolonged eugonad testosterone intervals while maintaining excellent disease control in men with oligometastatic prostate cancer"
Thank you. Very Interesting!
This is of course what got my attention
MDT combined with hormone therapy as part of an intermittent regimen improves eugonadal progression-free survival
MY MO has given me the option to stop ADT and go Intermittent, which I had been considering since I was at Undetectable levels. My recent PSA jump has given me pause...
Tall Allen has some contrary data.
He may see something in this study that we aren't seeing.
Agent 00-Scout: Yes this is quite an impressive analysis. Thanks for re-posting. Of course that is sort of what I am doing, after SBRT to my nodal oligo-mets in May (followed by Lu-J591 in Australia) I am doing very well on modified BAT. Sort of an extreme version of enhanced IADT. Even without that though, SBRT for oligo-mets with IADT is convincingly shown here to be beneficial in HSPC. Here's to "Eugonadal PFS" Cheers!
Hello Zen Master
This is sort of how I imagine my future... SBRT to mets if and when they appear and intermittent use of Estradol or Lupron and or 2nd gen to keep me from becoming resistant for as long as possible. Use of PSMA Pet scans to track progress.
Discussed this with Tang. The danger is using PSA to monitor progression when you are treating PSA. He said that patients were monitored with scans too. This is the difference between a clinical trial and real life. I thinks monitoring with scans is critical if anyone is going to attempt withholding ADT.
My point is that the decision to do cADT vs iADT should not rest on whether PSA is treated by MDT. Treating PSA by zapping largest mets may mask true progression.The potential harm lies in corrupting our best biomarker. If one needs a vacation from ADT, important to use scans.
Treating PSA by zapping largest mets may mask true progression.
Allen
You know my brain has been turned to mush by ADT.
I don't understand how zapping mets is treating PSA. I think of it as killing cancer cells.
Read this:
prostatecancer.news/2020/07...
Thank you once again TA
You continue to educate and inform me with your thorough knowledge of PCa and therapies.
Let me see if I can summarize what your article means to me as a Ogliometastatic man.:
My die has been cast and there is not much beyond what I have done so far ( RT Lupron + Zytiga) that will change my endpoint, ie: OS.
Once PCa escapes the capsule, one is on a curve of increasing disease that is growing exponentially. Without a game changing new therapy I have a probable life expectancy of 6-10 years no mater what therapies I do or do not do, with the later years being more difficult and painful as the disease increases unchecked. With todays technology none of the therapies are going to change that trajectory.
I am much more sanguine about what systemic therapies can accomplish than you are. Early intervention with intense systemic therapies have proven to delay progression and increase OS. IMO, the biggest opportunities are in combination therapies that kill cancer cells from multiple directions at once. There is also work to be done in stalling resistance/maintaining vulnerability to therapies, and in tailored therapies. The pace of new therapies is dizzying - the therapeutic landscape has changed dramatically in the 12 years I've been watching it.
the biggest opportunities are in combination therapies that kill cancer cells from multiple directions at once.
What is an example that may be useful to me going forward?
In fact, I'll post a new one such today or tomorrow. Meanwhile here are some effective combo therapies with Xofigo:
prostatecancer.news/2021/02...
It seems that the more toxic docetaxel dose could be reduced by the combination without any loss of efficacy
Was my only real disappointment in not getting in the combo arm of the Dora trial I am in. I was looking forward to a reduced dose of Dox this time around and read into trials Xofigo didnt represent much significance in SE's.
As it is I have the full dose of Dox, one in the tank so far, and felt the crash significantly. I think my memory of Dox crash SE's from 3 years ago was a bit missing in just how uncomfortable it can be.
SEs are usually worse over time. That's one of the reasons I think it's best to use it early.
Yep. This is my second time around with Dox. First time was 3 years ago at diagnosis.
I imagine 3 years of adt doesn't help in now again facing chemo crashes.
'The pace of new therapies is dizzying - the therapeutic landscape has changed dramatically in the 12 years I've been watching it.'
And yet the primary treatments by most Physicians is the same as 20 (or more) years ago.
Of course, most attention is focussed on advanced PCa - the patients most in need of new therapies. RP hasn't changed much since the 1980s, but there are many advances in RT.
I agree...combinations hold promise but dosing has been a challenge for targeted combos (e.g. CureMatch pathway approach ).
Adaptive therapy seems to hold much promise. I've been most impressed with concepts and a limited abiraterone trial from Bob Gatenby MD, Moffitt Cancer Center, Co-Director, Center of Excellence for Evolutionary Therapy, and Department Chair, Diagnostic Imaging. Maximum Tolerable Dose is archaic. You can hear more about his philosophy here...
There is also work to be done in stalling resistance/maintaining vulnerability to therapies
Stalling resistance is my game plan. Once I complete 24 months of ADT (10 months to go), given todays technology, what do you think is the best strategy to follow next.
Enjoy your cure!
I want to chime in and agree that your die is likely not cast at all. Your choices of ‘stick and move’ IADT and BAT may be best for now, but the arc of medicine continues to shorten, as TA. says.
I agree it can be discouraging when (apart from immunotherapies) it seems like almost every treatment is just a better variation on very old ones, which is mostly true. But it almost certainly won’t stay that way.
The concern I share with you is dying of this. Probably in my 40’s I started joking with friends that I was high risk for living a long life, given my superior fitness, happiness, habits. etc. My ‘gallows humor lite’ at the time suggested fear of centenarian decrepitude, which of course since been replaced by death by Pca a lot sooner than that . As a very experienced professional advocate and caregiver said to me, ‘it’s not how you want to go.’
However, my MO worked on BAT with Denmeade and was a big fan and early proponent of MDT, though I didn’t know that when I asked him early on how he would direct my treatment if I had a recurrence in 5 years. His first words were, ‘I have no idea’. I was perplexed for a second until I realized what he meant. Sanguine indeed. Stay strong and scouting!
We are all dying, you and I have just been given a likely timetable, which gives us a chance to live every day to it's max because we know how precious they are.
I agree wholeheartedly. I’ve used MDT along with Lupron and Zytega as I’ve ended my vacation and intend to do so again. My question for you is as follows: to date, I think your position has been that there is no strong clinical evidence that MDT has any survival benefit with or without other systemic treatments, but why not since it’s relatively safe as long as one is also doing systemic treatments (Lupton / Zytega etc). Is there anything more recent evidence that has made you more optimistic that MDT may in fact have survival benefits?
Schwah
You can be sure I will be enthusiastically spreading the word if there were.
I know…..just hoping….based upon what is known, if you were a betting man, would you bet that there is no survival benefit to MDT with or without concurrent systemic treatment?
thank you.
Schwah
I advocate hedging ones bet by using MDT in addition to ADT when it is safe to do so. If for no other reason, it always makes patients feel better that it may be accomplishing something.
And If there is nothing out there to indicate a survival benefit , why do most insurance companies have no issues paying for MDT, even if it’s not to reduce pain. We all know they usually do not pay if there’s no probable benefit.
Schwah
I have shown you all the "evidence" there is. Do you consider what an insurer will or will not pay as evidence?
BTW- There is a recent Phase 2 trial that suggests that prophylactic SBRT to asymptomatic, polymetastatic, "high-risk" bone metastases in lung, breast or prostate cancer decreases skeletal-related events (SREs) and increases survival.
"High risk" bone mets=bulky size ≥2 cm, junctional spine or posterior element, hip or sacroiliac joint, long bone with 1/3-2/3 cortical thickness.
• SREs (pain, fractures, spinal compression, spinal surgery or palliative radiation) were reduced from 29% to 1.6%.
• Mortality was cut in half during follow-up. The mortality decrease is from less surgery, less infection, and fewer hospitalizations.
You must admit that is a conundrum if you are correct and there’s no clinical proof that MDT increases survival yet most insurance companies will easily pay for non palliative MDT. It’s hard to think of any other examples of expensive medical procedures that have no clinical evidence of efficacy (other than palliative) that insurance companies regularly pay for with zero argument. Much easier to find the opposite…..Procedures that are proven effective that insurance companies are reluctant to pay for. I even asked my radiation oncologist if I had to say my L-5 met was causing pain to get it approved for SBRT. He said “no worries”. They always approve. “.
I guess I am belaboring the point in the hope that the insurance companies are seeing signs of efficacy for MDT that you somehow are missing. Perhaps they are using the studies showing reduced PSA from MDT, to justify efficacy , not realizing your viewpoint that the reduced PSA may simply be related to removal of a met, as opposed to actually extending survival?
Schwah
Do you seriously suppose that the insurance companies have some secret knowledge they are hiding from the rest of us? Or that they all believe that PSA is cancer?
By the way, they will also approve radiation to metastases in people who have dozens of visible metastases. I guess they assume it is prophylactic or palliative.
No….actually I was hoping you were wrong….lol…and you were misinterpreting the data on MDT. …but that doesn’t seem to happen much on the subject of PC….lol. Thx for your input TA…..
Schwah
All I'm saying is that there is no proof, and lacking proof, it isn't a good idea to give up on therapies for which there is proof. If you want to do MDT as well, and it is safe, why not?
so would include nuclear bone scans, CT scans and PSMA-Pet-Ct scans?
If you have bone metastases, NaF18 PET/CT is the most sensitive.
see my reply to Mateo below
Treating PSA by zapping largest mets may mask true progression.
Allen
You know my brain has been turned to mush by ADT.
I don't understand how zapping mets is treating PSA. I think of it as killing cancer cells.
Exactly, MDT decreases the tumor load and destroys cancer cells which know how to disseminate the cancer. These are cells which have learned how to live in tissues which they were not supossed to live. They are worse than the primary tumor.
For every met you can see, there are thousands you can't see. Only systemic therapy (ADT, chemo, etc.) kills the cells you can see as well as the ones you can't. Is there any value to zapping the biggest ones? We just don't know yet. Best bet is to do both, if safe.
If it works like Breast Cancer, there is no value to MDT.
killing cancer cells reduces PSA...yet the other unseen metastases are still there to continue the war ?
Agreed. There are tens of millions of cancer cells in a tumor that shows up in a PET scan. The smallest tumor that can be seen in a PET scan is about 5 mm. Each cancer cell in a met (whether seen or unseen) is capable of traveling and implanting in tissue reservoirs elsewhere.
what is avg micron size of a prostate cancer cell? How many cells make up a tumor of 5mmin diameter?
About 10 million in one estimate I saw from an MO
Wow!
Dear Allen, in my last PSMA Pet/CT they have seen three metastatic PLN with 2-3 mm and relatively low SUV. Do you think, they could have been false positive?
How low was the SUV max?
SUV peak 2,2-4,8 for the three PLN. On regular CT invisible.
I don't think any radiologist would think that an SUVmax below 3.5 is positive for cancer. 4.8 is low, but it depends on the background rate. There is often no CT correlate.
I don’t fully understand, did you mean „above 3.5“?
No. Lower SUVmax is less likely to be cancer.
Ah - got it! Positive in your sense means really positive. 😂 Many thx!
Positive means the test was positive for cancer; i.e., it is cancer.
That seems to be the issue. Scan technology (PSMA/ PET), and treatment need to catch up with PSA assay technology. You have a gap between undetectable PSA and cancer which is supposed to exist but cannot be seen and not treated. What to do?
Even PSA only tells you about tumors that have created their own blood supply,
Understood. So take a practical example in Dr. Scholz's vid. Say the man's PSA is over 0.2 (assume that is the nadir), but the best scan still cannot find the cancer. What do you do? Seems a grey area. Is it because there is no cancer or because the scan cannot find it? It may affect the QOL, etc.
We are talking about men who did not have prostate removed, right? And the normal PSA is 2.0 or 2.5, right?
Just curious. That's all.
I didn't see the video and have no idea what his situation is.
Here is the link. From about 5.00.
I don't watch videos, sorry. I haven't got time.
I watched for a change and see why you tend not to watch. No personal disrespect intended towards the Dr. but seemed to be a lot of loose lipped babble that would turn patients into the type who have forced Dr.'s to prescribe antibiotics for viruses.
Just an FYI, Dr. Scholz is the director of the Prostate Cancer Research Institute and has over 25 years of dealing solely with PCa. He knows his craft well.
Totally agreed. Our interest is in QoL, extend and kind of treatment (expensive without insurance, for a start) etc.
The vid was made some time in 2021. The study which defined the LT DFS threshold as PSA 0.2 came out in 2020. For a doctor who treats thousands of patients a year, plus runs a public non profit info organization, he might not have caught up at the time. Dr. Scholz is doing a remarkable job. No mistake about it. But like he others are saying, the science is developing so fast that it is easy to miss a couple of things from time to time. For the layman , it would be nice to get some clarification. That's all.🙂
Chad Tangs EXTEND trial is the subject of this thread. I participated in that trial. If I remember correctly debulking via radiation was a requirement of the trial. I had my prostate zapped by Dr Tangs team when I entered the trial.
Interesting and very good reading….ok, dumb questions…what is an example of met directed therapy or MDT? Is that a local met that is treated with radiation?
distant met treated with SBRT, usually
gotcha. Thank you TA
Interesting indeed...
My MO just a few short years ago wasn't so hot on "Whack-a-mole" modality... But with my recent progression, is something he proposed. So the industry is coming along, lol.
Watching this thread!
Not what you're looking for?
You may also like...
STOMP - Oligometastatic PCa.
An update on the STOMP Trial.
STOMP is a small (Phase II) trial involving metastases-directed...
New Protocol of Intermittent ADT for Patients With Metastatic PCa
New Chinese study below [1].
"In the 65 metastatic prostate cancer patients in group 1, androgen...
FDA Approves Darolutamide Plus Docetaxel for Metastatic Hormone-Sensitive Prostate Cancer
Other triple therapy approved by the FDA. The article has the basic results of the ARASENS trial....
Oligometastatic PCa
Looking for more info on Oligometastatic PCa- wondering if that is what my dad will be defined...
Intermittent secondary ADT
I'm currently taking Xtandi while waiting to start a CAR-T trial. Due to the way scheduling is...
Oligometastatic PCa - There’s Hope!!
Rising PSA after radiation and ADT
