Radiotherapy In The Definitive Manage... - Advanced Prostate...

Advanced Prostate Cancer
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Radiotherapy In The Definitive Management Of Oligometastatic Prostate Cancer

6357axbz
6357axbz
25 Replies

Someone recently left a link to the subject study which I forwarded to my RO. Here was his reply (the original link is below):

Thanks for the paper. Ultimately these retrospective reviews will always show a benefit with radiation treatment because they compare men with low volume disease to men with high volume disease. Ultimate a randomized trial is published we cannot however say that one is better than the other.

ncbi.nlm.nih.gov/pubmed/314...

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Tall_Allen

Smart RO.

Most people who site studies that they copy off the internet don't understand the import of the research they are quoting. Unfortunately, not all researchers are as careful about their wording as they ought to be either.

The lead author of the study you cited is working on an actual randomized clinical trial (see below), which he tells me, he will publish soon. Unfortunately, 6 months of follow up isn't nearly long enough, and his conclusions based on PSA will only confound the issue. There are some more randomized trials in the works that will tell us more:

pcnrv.blogspot.com/2017/07/...

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6357axbz
6357axbz
in reply to Tall_Allen

TA, how would you respond to tango65. I’m just looking for objectivity. Thanks.

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Tall_Allen
Tall_Allen
in reply to 6357axbz

My response is the fact that men with hormone-sensitive PC have a longer life expectancy than men with castration-resistant PC is as unsurprising a finding as they come.

Your RO is not addressing that study in particular (which tells you nothing useful), but he is saying that all studies on oligometastatic PC (which is what he means when he says "low volume disease") so far have not proven that there is any survival advantage to oligo metastatic treatment (that is absolutely true).

Perhaps you can tell me in your own words what you saw in the study that you found to be interesting.

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6357axbz
6357axbz
in reply to Tall_Allen

I thought it indicated a benefit for using MDT

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Tall_Allen
Tall_Allen
in reply to 6357axbz

No - it did not. The only way to show a benefit for using MDT is to compare it to what happens if MDT is not used. This was not done.Cancer growth follows an exponential growth curve, which means it is very slow at first, but increases over time. So a few years between the first few detectable metastases may be normal, whether they are treated or not.

The questions you should be asking are:

• What happened when they did MDT?

• What happened when they did not do MDT?

• Did they measure what happened by something other than "local control" or "biochemical control"?

MDT certainly shrinks the tumors it is aimed at (local control) and those larger tumors account for most of the PSA (biochemical control), but what about the tens of thousands of cancer cells that form tumors too small for any scan to see, that are in systemic circulation, or are hiding in reservoirs waiting to grow? Considering the rapid growth of cancer cells, does MDT of the largest metastases really delay actual progression (and not just PSA)? This is unknown so far, in spite of what you may read on this site.

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6357axbz
6357axbz
in reply to Tall_Allen

That makes sense. Thank- you TA

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tango65
tango65
in reply to 6357axbz

To my knowledge, nobody in this group is saying that direct treatment of oligo metastatic cancers offers a survival advantage. Direct treatment of these cancers may offer the possibility of delaying for awhile the use of systemic treatment.

Many centers of excellence (JHopkins, Sloan Kettering etc) are using direct treatment of oligo metastatic cancers. The paper Patrick posted showed the experience with direct treatment of oligo metastatic PC at JHopkins.

Doctors who take care of patients and have extensive clinical experience in the treatment of PC consider that direct treatment of oligo metastatic cancer should be offered to the patients. I consulted with Dr Michael Morris at the MSKCC about using this treatment and he agreed that it was a good plan.

Randomized control studies are being done or will be done and in about 5 to 10 years we may know if direct treatment of oligo metastatic cancer offers a survival advantage.

Most of us do not have 5 or 10 years . We should evaluate and decide about treatment using the options given to us by real Drs with expertise, vast clinical experience and responsibility in the treatment of patients with advanced PC.

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Tall_Allen
Tall_Allen
in reply to tango65

The problem with delaying systemic treatment based on MDT is that the decision to initiate systemic treatment is based on PSA. MDT reduces PSA by eliminating the biggest tumors - the main source of PSA. This is called "treating PSA" instead of treating the cancer. So I'm not at all sure that it is a good idea to delay systemic therapy based on MDT. In fact, I suspect it's a bad idea because it allows the systemic micromets to multiply, increasing the load of invasive cancer cells. I fully support doing both: ADT for systemic therapy coupled with MDT for local therapy - there's little risk in that (as long as the SBRT is in a safe place).

Many doctors I work with are skeptical of any benefit. It depends which doctor you talk to. There is no data, so it is all speculation. Here is what Ken Pienta (one of the top urologic oncologists in the US) at Johns Hopkins has to say (you can just listen to the first half). It is sobering about the sheer numbers of cancer cells that are not treated by MDT. Based on this, why would anyone delay systemic treatment just because the plasma PSA is lower?

urotoday.com/video-lectures...

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Rocketman1960

It's all about doubling time.

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Tall_Allen

What is about doubling time?

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Rocketman1960

Progression of Pc. I agree with everything you wrote. Anyway, the actual number for PSA is far less important than the rate of change. And the lower you can get that number, the more time you buy.

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Tall_Allen

You are conflating a biomarker for progression (PSADT) with clinical progression. If you "treat PSA," you can extend the PSADT without necessarily slowing down the cancer.

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Rocketman1960

No argument. Scans are also needed.

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Tall_Allen

Not "also," instead of. If one has tampered with PSA, all one has left are scans.

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Myriammole
Myriammole
in reply to 6357axbz

What is MDT?

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6357axbz
6357axbz
in reply to Myriammole

Metastases Directed Treatment

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tango65

I do not know what your doctor is talking about. The authors of this study never compared men with low volume disease to men with high volume disease.

The population studied was composed of 156 men with oligometastatic cancers (less than 5 metastases). All the patients received direct radiation therapy of their metastases. The median follow up was 24.6 months .

The authors determined that the median biochemical progression free survival in these 156 oligometastatic patients was 12.9 months. Oligometastatic patients with hormone sensitive cancers had a median BPFS of 17.2 months, meanwhile oligometastatic patients with castration resistant cancer had a median BPFS of 7.2 months.

Nowhere there is a comparison of these patients with patients with a large number of metastases.

I believe your doctor and others did not understand what they read.

redjournal.org/article/S036...

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NPfisherman
NPfisherman
in reply to tango65

Agree with Tango here...The part to me that is what should be looked at is using longer ADT with SBRT on Oligometastatic patients--hitting it hard early--from the article:

We analyzed 28 men

with HSOPCa treated with a course of peri-RT ADT (median 4.3 months) with recovery

of testosterone. At median 33.5 month fup, 20 have not developed bPFS, median bPFS

has not yet been reached, and 24 month bPFS was 77%...

Slowing progression buys time..at 33.5 months bPFS had not been reached.....especially now with 2 new classes of drugs and a CAR-T with vaccine treatment that looks promising just 4-5 years away...

Don Pescado

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are2yvr
are2yvr
in reply to NPfisherman

I’m no doctor, but what this sounds like is that 28 guys with low volume disease upon diagnosis (“de novo”) were treated with BOTH SBRT and systemic therapy by way of ADT and were then taken off ADT while still hormone sensitive.

They then trailed this small group of guys for 3 years on average - three years off ADT - and at the point they stopped tracking them, three quarters or so were still cruising - no drugs, no hormones.

We don’t have OS (overall survival data), but you can presume if they are still hormone sensitive and they relapse down the road, they still get a fresh clock with combined therapy like ENZA+ADT or Abi available per Titan and Enzamet.

The paper makes the point for a small subset of limited met guys maybe this is helping to clarify who benefits most. That’s what the whole multivariate analysis thing is trying to stratify for.

Given the PFS or time till next treatment data for this subset, this is a Big Deal especially when compared to the SEER database for newly diagnosed metastatic men.

The point that’s being driven home is that yes they are doing great things for oligo - but SBRT isn’t enough. You need all sites of disease treated including the mothership, the satellites, and the cables connecting the satellites to the mothership.

For any fans of Hopkins, this study was the precursor to the Total eradication of disease trial run out of Pienta’s lab, whose data is not yet mature. The TeD trial made some tweaks - added RP not RT to the primary, added Chemo upfront with short course Abi or Enza, and added EBRT at the RadOnc’s discretions. Basically a more hard core version of what was just published, with greater weight given to systemic.

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NPfisherman
NPfisherman
in reply to are2yvr

My understanding is the same...There are several oligo guys and I watch their posts....Schwah had 3 lesions, was put on Z+P+ADT+Zometa and Celebrex-- got SBRT---after 21 months "undetectable" , he is on ADT vacation...my brother, jdm3 had 1 lesion, and was on Z=P+ADT, and had SBRT, after15 months, now on ADT vacation--took dutasteride and got rapidly to high normal T--3 months later--still "undetectable".... May God allow them to remain "Undetectable" forever....

I think the real benefit if by initiating systemic therapy early---possible Docetaxol (high tumor burden)+Z+P+ADT, and then SBRT.....

I took out the "mothership"--had RP, and took Z+P+ADT and had SBRT--10 months in and test soon...hoping to remain amongst the "undetectables"....

The reality is that this has shown advantage here for driving the disease backwards. A Phase 3 study is to be done and we will get the final word on SBRT for Oligometastatic disease... I believe tango65, George71, myself, and many others will be correct about the benefit.

Can't tell you how much crap we have taken from one poster here about how SBRT has no proven value in oligometastatic disease... I guess we could all wait for the randomized double blind study, but then we might lose the benefit.... We bet our lives.....Does he have anything of value to bet close to what we throw on the table ??

NOPE !!!! Sometimes, when you are in our situations, you weigh the benefits and negatives, and go for it or not ,..these subsets indicate that there is benefit....

All the best,

Don Pescado

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are2yvr
are2yvr
in reply to NPfisherman

Everyone’s got their own way of trying to contribute. Foe me, if I have an onc who tells me a treatment won’t work (even if he’s wrong), he could very well be triggering a negative placebo effect (yes, it’s a thing) and my brain could do the sabotaging. Conversely, they could be helping to fight off mets even if giving me water, if I trust them. The whole thing still confounds.

I appreciate anyone who’s a good interpreter of data. And kibitzing with my surgeon the other day, I was surprised to discover how many men, even with stage 3 disease, will outright refuse certain treatments unless they see the data and are given “guarantees”.

I too am oligo dx and undetectable, riding the crest of this crazy aggressive nuclear bomb treatment. And my first pitch at treatment from an esteemed physician was Standard of Care ADT that’s it. So when I look at that data, 21 months or whatever it is to failure, then a few years on second line... well, I can only roll my eyes, and say no thank you.

I’ve been following the board since dx and you know there were people a year ago, two years ago hammering the table saying “there’s no benefit to treating the primary!” And “there’s no benefit to treating the mets!” and some people listened and good for them.

Now I think it’s pretty universally accepted (just saw another consensus paper on Om from, this time, the Dutch last week) that 1. Oligo is an accepted state; 2. Cyto reduction and managing tumor load prolongs, at the least, time to next treatment; and 3. There appears to be a small subset of guys who have carpet bombed low volume metastatic prostate cancer and have sustained remission for multiple years.

Given that we’ve only been seeing this approach for less than 5 years, it’s tough to say whether anyone is cured, but docs talk, oncs talk, they share data privately, and many of them have guys that are doing really well. You think it’s some sort of weird coincidence that there are like 20+ global trials now underway on Oligometastatic de novo disease from basically none just 4 years ago?

I understand the frustration with skeptical minds and that people who are hard wired differently, like a cartoon of a guy in a burning house asking the fireman “is it ok to leave now?”

But getting back to my main point, treating all sites of disease here for newly diagnosed hormone sensitive men, then taking them off ADT and watching 3 quarters of them STILL off adt at 2, 3 years plus- how the f is that not cause for celebration?

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NPfisherman
NPfisherman
in reply to are2yvr

I agree....however, if you read above, you will find the guy with the largest following here will disagree... My philosophy is beat it down as far as you can early, and you buy time...quality time...not just existing, but family fun, go to work, enjoy life time...QOL counts and it is not something they are looking at in these studies....just OS, and PFS... I do believe we will find OS and PFS will be higher with early SBRT in oligometastatic HSPCa... There is a video with Dr. Eugene Kwon with him showing cases where they treated oligo patients aggressively early including SBRT, and had long remissions...one guy was 8 years and still "undetectable"...

Stay inside the SOC box and you have a date with the Grim Reaper... This is a war...and we can't always wait for double blind randomized trial results...On a good note, 2 new classes of drugs--not AR inhibitors are finishing up Phase 2 and on to Phase 3--add ons with Zytiga, Enza, or Apalutamide...The fight will change dramatically in the next 5 years...

Good luck, brother....

Don Pescado

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AlanLawrenson

Could you clarify your treatment: Z+P+ADT+Zometa and Celebrex-- got SBRT. and was on Z=P+ADT?

I am unsure what Z and P are?

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NPfisherman

Zytiga and Prednisone...

Don Pescado

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NPfisherman
NPfisherman
in reply to tango65

tango65

From a different version of this article:

On multivariate analysis, peri-RT ADT, smaller gross tumor volume, and hormone-sensitive disease were significantly associated with improved bPFS, according to the investigators.

“These findings appear to indicate the optimal time for intervention is with lower volume disease,” the authors wrote.

I am glad I chose stereotactic radiation to the one lesion found by Axumin scan--post RP....there are several brothers who have done similar...Schwah is one...he just took an ADT vacation...These brothers like me were on Zytiga, ADT, prednisone during SBRT, and Schwah received Zometa and Celebrex which also showed a survival benefit...

There are never guarantees with this disease, but there is no reason not to "stack the deck" in one's favor...

Take care, amigo....

Don Pescado

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