Unwarranted conclusions about oligometastatic treatment

Redwing...thanks for your answer.
Would you think that if we looked at the same cohort at the 7, 10, and 15 year mark we would see an increasing narrowing of differences?
The theory would be that the incremental 18 of additional deaths in the delayed group died at the 60 month point because their tumor burden increased during the first 20 months on no ADT to a point that the last 30 months of ADT could not overcome the tumor burden but that after the 60 month point the playing field ( death rate) would be leveling since the survivors of the delayed group would have demonstrated their cancer's progression was slowed.

You more often see the Kaplan-Meier survival curves separating with time as more death events occur.

Patients with a PSADT of less than 3 months at the start were excluded from the study because immediate ADT was definitely indicated for them.

Patients may have been offered ADT when any of the following occurred :
(1) PSADT<12 months with a PSA≥10 ng/ml
(2) PSADT≤6 months
(3) metastases detected or symptoms

Break60 said...
Redwing
I assume TA will chime in re: the accuracy of your hypothesis. However, not addressed is what the gents who delayed ADT did in the interim. If they had focal treatment to visible mets along with a one month Lupron shot would those 40 guys still be deceased? That's the question I'm trying to get answered. And I find it difficult to believe that their survival would be extended .
Bob

I think he already did. But anyway, TA has the most perspective on that of anyone I've heard. I understand what you're asking about; I've wondered the same thing. For what it's worth, I tend to agree with TA's viewpoint (hoping I'm not mischaracterizing it here). Attacking the first few "oligomets" is of little value unless they're symptomatic. Once the bad prostate's metastatic seeds have blown about the system, it's just a matter of time until they implant and sprout somewhere. There are probably at least thousands of them floating around, as has been discussed earlier here.

The only reason I can see to whack a single early met is if its growth is specifically problematic, "clinical". If it's symptomatic, as in bone pain, urethral obstruction, pressing on nerves in the spine, things like that, then sure you need to go after it.

But say there's a "hot" lymph node that can be detected. Well, so what? It could even cause PSA to rise. Again, so what? Through sensitive scans finding that to be the cause of a PSA rise, perhaps you could even better justify delayed treatment. It doesn't make subsequent metastases appear any faster by its existence. Conversely, eliminating it doesn't stop the other later-blooming metastases from sprouting when they're ready.

The argument I suppose would be whether or not an asymptomatic metastatic lymph node actually increased the rate of later metastases. My understanding however is that the first mets are simply that, the first to show up in a somewhat lengthy process. The next ones show up a year or two later no matter what you do to the first one. If stopping that one delays the next ones, then there would be an advantage to whacking it. Simply lowering the PSA is not really of any value by itself. To me, that's the real question. Does taking out the first mets slow the next ones to develop?

The ability for the cells to survive outside the prostate signals to me a major shift in the disease course. Normally, they can't live away from their brethren in the prostate environment. If some show up having grown elsewhere, well then they've become a new kind of wild cell with a new ability to migrate. Once that's happened, you're just fighting a holding action.

If you see the first bright yellow dandelion bloom in your yard, and you run out and dig it up, does that stop all the other dandelions from popping up? No, they're already there, just taking longer to appear. You know if there's one, that seeds exist for many more already. It's too late for a pre-emergent to block them, and now you have to drag out the broad-leaf weed killer and hit them all. Maybe not a great metaphor, but it's a way I think about it.

For me, as a "very high risk" case with primary Type 5 cells, cT3a stage and all, I'm looking for a systemic effect of ADT in damping the growth rate of all metastases, detectable or not, micro, macro, asymptomatic. This is mentioned in some studies, an "unplanned subgroup analysis", that guys like me benefit from early and continuous ADT due to the high likelihood of developing symptomatic or "clinically significant" metastases earlier rather than later. Those type 5 cells are readily metastatic, and are bad actors even if only found as tertiary in a biopsy.

I'm curious about the quality of life for the delayed ADT group. To me, the overall survival numbers are questionably different enough to warrant living that whole time on ADT, vs. waiting to start it later. I know what living on ADT is like; I did it for 3 years already. What's life like with a reasonably aggressive case if you don't do it early?

If one waits, do painful bony metastases show up earlier at say, year 4, and then one lives fitfully with that situation the remaining years? Or, conversely, if on ADT, do the same events begin later, and rocket up lethally only at the end, say in the last year or so? So, are you trading off years of moderate physical impairment due to ADT, vs. years of a different impairment of painful metastases without ADT?

Or, can you whack a painful metastasis, stop it, and thus avoid ADT until very late?

Redwing,

if the TOAD study does not prove a "a clear survival benefit of immediate", for me it just tells me that you should not think you HAVE to start ADT immediately. This does not prove that later is better. I think the start of ADT should be an individual decision which you and your MO make - and can be anywhere between immediate and late.

George

Mattamx

I'm not hung up on the small survival advantages reported by the various treatments either. If everyone had the same results of these treatments , like a few months of additional survival, I seriously don't think that many folks would sacrifice QOL for a few extra months on this earth. The confounding factor to me is that some guys live for many many years with a really bad prognosis and manage to have a reasonably good life on HT.
You seem to have convinced yourself that you're toast no matter what you do. I admire your fortitude particularly for a young guy.
I'll be getting the advice of my RO tomorrow after he's seen my axumin scan results. I'm thankful that I've heard from so many of my brothers in the trenches to help me decide on the best course of action.
Bob

These last few posts have dealt with the question of " what difference it all makes " once the cancer has left the gland, wherever it might have gone. The more one reads about prostate cancer the one more realizes that if at the time of diagnosis the cancer is a Gleason 7 ( or higher ) and outside the gland , it is chronic and not curable.
You just don't see cases where someone says "I was a Gleason 7 , had a prostatectomy , had positive margins and SV invasion, got RT and have not had any biochemical recurrence for 10 years."
Within the last 5 years ADT is being prescribed co incidental with Salvage RT and we see PSA control for the length of the ADT but 6 months after ADT stops we are seeing recurrence. To me it is impossible to tell the efficacy of the RT since the control evidently came from the ADT.
Since early ADT is being prescribed, and since many men have recurrence after they stop ADT, we are now seeing ADT being prescribed till castration resistance, which for many men, who consider themselves fortunate that ADT continues to work , can be a long time.
Perhaps without basis, I am not convinced that delaying hormone therapy until visible metes appear, or beyond, is a stupid idea. My reason for that is that in most cases castrion resistance will occur within 36 months, and you are onto chemo, outrageously expensive second line hormone therapy and then trials and the unknown.
Assuming the cancer will be hormone resistance in a 36 month cycle, aren't you pushing back that endpoint by the time you stay off ADT?
Some will say the tumor burden will be greater at that time and the other therapies will be less effective, etc., but realistically after ADT there is nothing left that is proven to work.

I'm in my 8th year of Gleason 9, mets to bone. It's not for everyone, but I've chosen IHT and spot radiation when anything shows up. My PSA has been under .01 ever since my surgery 7.5 years ago...current f18 scan is good.

Does spot radiation do any good? Who knows. I do know that psychologically it allows me to deal with things better knowing I'm hitting it back with several therapies simultaneously.

Is early HT better? Who knows. It just the road I guess I find myself.

And IHT---Somehow even with my G9,etc...I've been able to have normal testosterone for 4 of those 8 years...and really look forward to those vacations...although, really I've been fortunate with the side effects of HT.

Sometimes there is no right or wrong..we just choose the best that we can at any particular moment in time.

JL

This thread is nicely addressing my situation with my recently discovered pelvic node disease and is clarifying.

What's clear from the discussion is thats its unclear treating oligomets is life extending or not. But if it can't hurt, the attempt is understandable and reasonable. But what if it can hurt when you get receive treatment that might not extend survival yet will compromise your health? I feel caught in a stalemate of unclear odds and maybes. Hearing differing opinions from different docs doesn't help at all. This is the murky world of recurrent disease I simply have to get used to it appears. Take your best guess and move forward.

This is what I believe (hope) to be true. There is an agent or cocktail of agents out there on the horizon which will either cure or successfully manage metastatic prostate cancer long term. Until it's discovery I have to do what I can to hang on and extend my life to get to that treatment. I feel this intensely and from observing the rate at which new treatments are being created and evolving I can't help but maintain confidence the hope is warranted. Perhaps I am in denial, I really can not tell.

I do know that I am an eternal optimist and refuse to accept defeat. The refusal is suspect in creating bias, I know, but I can't help but sense hope if I simply stay alive long enough. If I do surrender into hopelessness I believe I will fall like a stone into a depression that I am afraid I will never emerge from. The fear of that depression definitely clouds my judgement though and I feel I am left as a puppy chasing its tail in trying to navigate what to do and how to accept life as a metastatic patient. Am I being a child here? ***....





Sent from my iPad

Break60, one thought on your ADT3 initiation for a met. Lupron has a lengthy induction phase, up to a month to reach castrate levels. Maybe you could use Firmagon for immmediate testosterone suppression, then switch over to Lupron for a longer term? Firmagon knocks it down very fast (castrate level within about 3 days for 96% of people), almost as fast as orchiectomy.

Bob-

I think your best choice is to start on ADT immediately. I don't know of any proven benefit of ADT3 over a single agent. The only important effect is that you take whatever is needed to prevent activation of the androgen receptor. Some MOs use Casodex only, some use Lupron (or Firmagon or Trelstar...) only, some combine Casodex and Lupron. A recent RCT showed no benefit to adding Avodart into the mix, so that is at least one you can avoid.

You may have noticed a post recently by a patient of Howard Scher's (certainly one of the best MOs anywhere), where he was taking only 1 or 2 50mg Casodex a week. This was enough to bring his PSA down to undetectable levels, yet keeps his serum testosterone high enough that he feels good - a win-win. He also takes tamoxifen to prevent breast enlargement.

There are lots of ways to do ADT and I hope you have a good MO who is willing to discuss all those options with you.

As for the radiation, it isn't hard to find an RO who can zap it in 3-5 treatments of SBRT. The last thing you want is a fractured femur down the road, and this can help prevent it. I agree with you that IMRT for this type of thing is a relic of the past, and all professional associations warn against it.

Wow, that a weekly dosage of Casodex was enough in that patient to acheive such a drop in PSA is something to remember. I have osteoporosis and am freaked out about eternal ADT I must say. To find a workable balance with a single oral agent would be great and I would experiment with that for sure if it would be an option for me.

Hi Bob, you have been through it all I see and if I had to guess, you're a patient of Dr, Meyers judging by you going to Datolli, Sand Lake and your treatment protocol. You are quite the warrior, it's obvious.

Dr. Meyers no longer takes patients, I've tried. If you don't mind me asking, what do you think has helped the you most with PSA control? Also, I've never communicated with anybody that had an estradiol patch and have alwways been interested in that. I know Dr. Meyers prescribes that for menopausal symptoms and for preventing osteoporosis. I suggested as much to my oncologist and an endocrinologist and they brushed it off. I wish I would have had one though as it made sense to me and I ended up with further bone loss after treatment. Did it work for you? Any side effects from that like enlarged breasts?

I would not care about that in light of saving bone if it works.