MDT and Intermittent ADT for Oligomet... - Advanced Prostate...

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MDT and Intermittent ADT for Oligometastatic PCa

Scout4answers profile image
77 Replies

Posted on other PCa board by NPFisherman, think it is relevant to some here as well

urotoday.com/conference-hig...

77 Replies
cesces profile image
cesces

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.

cesces profile image
cesces

"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"

cesces profile image
cesces

Thank you. Very Interesting!

Scout4answers profile image
Scout4answers in reply to cesces

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...

cesces profile image
cesces in reply to Scout4answers

Tall Allen has some contrary data.

He may see something in this study that we aren't seeing.

Nusch profile image
Nusch in reply to cesces

Let’s wait for his feedback.

in reply to Scout4answers

Do you have MDT? If you don't then the MDT part cannot be performed so you'll be left with IADT which will only be meaningful if your T returns to normal levels. At that point you'll find out how aggressive the cancer is...if it's like mine it'll come roaring back.

Scout4answers profile image
Scout4answers in reply to

see my reply to Mateo below

in reply to Scout4answers

I'm not sure how that works but I sure you do😜

MateoBeach profile image
MateoBeach

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!

cesces profile image
cesces in reply to MateoBeach

"modified BAT"

May I ask how you modified it?

Scout4answers profile image
Scout4answers in reply to MateoBeach

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.

Tall_Allen profile image
Tall_Allen

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.

Tall_Allen profile image
Tall_Allen in reply to Tall_Allen

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.

Scout4answers profile image
Scout4answers in reply to Tall_Allen

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.

Tall_Allen profile image
Tall_Allen in reply to Scout4answers

Read this:

prostatecancer.news/2020/07...

Scout4answers profile image
Scout4answers in reply to Tall_Allen

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.

Tall_Allen profile image
Tall_Allen in reply to Scout4answers

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.

Scout4answers profile image
Scout4answers in reply to Tall_Allen

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?

Tall_Allen profile image
Tall_Allen in reply to Scout4answers

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...

CAMPSOUPS profile image
CAMPSOUPS in reply to Tall_Allen

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.

Tall_Allen profile image
Tall_Allen in reply to CAMPSOUPS

SEs are usually worse over time. That's one of the reasons I think it's best to use it early.

CAMPSOUPS profile image
CAMPSOUPS in reply to Tall_Allen

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.

jac_j_sp profile image
jac_j_sp in reply to Tall_Allen

'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.

Tall_Allen profile image
Tall_Allen in reply to jac_j_sp

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.

Rhinochaser profile image
Rhinochaser in reply to Tall_Allen

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...

open.spotify.com/episode/2S...

Scout4answers profile image
Scout4answers in reply to Scout4answers

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.

Tall_Allen profile image
Tall_Allen in reply to Scout4answers

Enjoy your cure!

London441 profile image
London441 in reply to Scout4answers

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!

Scout4answers profile image
Scout4answers in reply to London441

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.

Schwah profile image
Schwah in reply to Tall_Allen

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

Tall_Allen profile image
Tall_Allen in reply to Schwah

You can be sure I will be enthusiastically spreading the word if there were.

Schwah profile image
Schwah in reply to Tall_Allen

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

Tall_Allen profile image
Tall_Allen in reply to 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.

Schwah profile image
Schwah in reply to Tall_Allen

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

Tall_Allen profile image
Tall_Allen in reply to Schwah

I have shown you all the "evidence" there is. Do you consider what an insurer will or will not pay as evidence?

Tall_Allen profile image
Tall_Allen in reply to Tall_Allen

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.

ascopost.com/news/october-2...

Schwah profile image
Schwah in reply to Tall_Allen

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

Tall_Allen profile image
Tall_Allen in reply to 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?

Tall_Allen profile image
Tall_Allen in reply to Tall_Allen

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.

Schwah profile image
Schwah in reply to Tall_Allen

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

Tall_Allen profile image
Tall_Allen in reply to 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?

6357axbz profile image
6357axbz in reply to Tall_Allen

so would include nuclear bone scans, CT scans and PSMA-Pet-Ct scans?

Tall_Allen profile image
Tall_Allen in reply to 6357axbz

If you have bone metastases, NaF18 PET/CT is the most sensitive.

Scout4answers profile image
Scout4answers

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.

tango65 profile image
tango65 in reply to Scout4answers

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.

Tall_Allen profile image
Tall_Allen in reply to tango65

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.

in reply to Tall_Allen

I think they should use the term nano-metastatic or pico-metastatic to give more of an emphasis on just how small the cancer cells are....micro, even though very small seems to have lost it's significance in the layman's understanding and appears to give the impression it can be treated.

Tall_Allen profile image
Tall_Allen in reply to

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.

fmenninger profile image
fmenninger in reply to Tall_Allen

what is avg micron size of a prostate cancer cell? How many cells make up a tumor of 5mmin diameter?

Tall_Allen profile image
Tall_Allen in reply to fmenninger

About 10 million in one estimate I saw from an MO

fmenninger profile image
fmenninger in reply to Tall_Allen

Wow!

Nusch profile image
Nusch in reply to Tall_Allen

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?

Tall_Allen profile image
Tall_Allen in reply to Nusch

How low was the SUV max?

Nusch profile image
Nusch in reply to Tall_Allen

SUV peak 2,2-4,8 for the three PLN. On regular CT invisible.

Tall_Allen profile image
Tall_Allen in reply to Nusch

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.

Nusch profile image
Nusch in reply to Tall_Allen

I don’t fully understand, did you mean „above 3.5“?

Tall_Allen profile image
Tall_Allen in reply to Nusch

No. Lower SUVmax is less likely to be cancer.

Nusch profile image
Nusch in reply to Tall_Allen

Ah - got it! Positive in your sense means really positive. 😂 Many thx!

Tall_Allen profile image
Tall_Allen in reply to Nusch

Positive means the test was positive for cancer; i.e., it is cancer.

anony2020 profile image
anony2020 in reply to Tall_Allen

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?

Tall_Allen profile image
Tall_Allen in reply to anony2020

Even PSA only tells you about tumors that have created their own blood supply,

anony2020 profile image
anony2020 in reply to Tall_Allen

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.

Tall_Allen profile image
Tall_Allen in reply to anony2020

I didn't see the video and have no idea what his situation is.

anony2020 profile image
anony2020 in reply to Tall_Allen

youtu.be/pC7SKfrTPFc

Here is the link. From about 5.00.

Tall_Allen profile image
Tall_Allen in reply to anony2020

I don't watch videos, sorry. I haven't got time.

CAMPSOUPS profile image
CAMPSOUPS in reply to Tall_Allen

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.

V10fanatic profile image
V10fanatic in reply to CAMPSOUPS

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.

anony2020 profile image
anony2020 in reply to CAMPSOUPS

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.🙂

6357axbz profile image
6357axbz in reply to anony2020

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.

anony2020 profile image
anony2020 in reply to 6357axbz

Thanks for info. Good to know. Seems other doctors prefer to see how far ADT+ and/or Chemo takes the PSA down before going RT. Guess every one has different clinical experience and treatment depends on each person's state of health etc.😀

maley2711 profile image
maley2711 in reply to Scout4answers

killing cancer cells reduces PSA...yet the other unseen metastases are still there to continue the war ?

cesces profile image
cesces

Then again see:

mdlinx.com/news/how-tumors-...

fmenninger profile image
fmenninger

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?

Tall_Allen profile image
Tall_Allen in reply to fmenninger

distant met treated with SBRT, usually

fmenninger profile image
fmenninger in reply to Tall_Allen

gotcha. Thank you TA

Cooolone profile image
Cooolone

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!

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