Unwarranted conclusions about oligometastatic treatment

Interesting.

All of my pelvic lymph nodes were irradiated to 50.4 Gy in my primary therapy even though nothing was detectable; it was preventative as Mack Roach has recommended.

So, if I should end up with a recurrent "active" lymph node, could there be more radiation given to it? My understanding has been that's not possible. And going after it surgically would probably be of limited value, again as you point out based on what's known about metastatic progression.

Just curious, as long as the topic has come up again.

"Oligometastases is a disease concept that is defined by a state of limited systemic metastatic tumors for which local ablative therapy could be curative. By definition, the purpose of local treatment for oligometastases is cure, and the primary outcome to be analyzed should be disease-free survival."

When it comes to treating cancer, find it and kill it is always good advise..

I found the blog posting associated with this thread to be particularly insightful, even for the Tall One.

Paul,

I would love it if he would respond, and perhaps I will forward it to him. I've met him, and know him to be compassionate and enthusiastic about his work. I did watch the video of his PCRI presentation, and have a few comments about it:

• It was a presentation to patients, not doctors. He is obviously trying to give patients with metastatic disease hope. If he went further than the data allow, his heart is in the right place. As he stated at the end, he was offering his opinions, not facts.

• He showed a score of before and after PET scans, showing how radiation or surgery can result in excellent local control of detectable metastases. PSA disappeared along with the mets, as we would expect. Ironically, he started the presentation with half a dozen cases where patients died despite no detectable PSA, and said we have to be cautious about using PSA as the only tool to monitor progression.

• In all the cases but a couple, he offered 2-year PSA control as the outcome. Two years is not enough.

• Case studies are very useful for forming hypotheses. Pubmed is full of case studies of "miraculous" remissions. Kwon did not show the cases where it didn't work, except one. This is where science comes in - observations like his have to be tested in randomized clinical trials. "Gee-whiz" presentations are exciting, but what we want to know is if it really works, how much it works, and in whom it works.

Oddly, I have not seen any announcements of a such a randomized clinical trial from the Mayo Clinic. Last year, they began a non-randomized trial in castration resistant men, but that's all I've seen from them so far.

There is one at Johns Hopkins that uses their DCFPyL PET for early detection, and they expect to report some preliminary outcomes as early as next year. Unfortunately, it is a small study and not long-running enough to detect survival differences. Here are details, if any are interested:

/clinicaltrials.gov/ct2/show/NCT02680587

Other randomized clinical trials are ongoing in London and Montreal that will have larger sample sizes and are scheduled to run long enough to detect survival differences.

If you get a PSMA PET/CT showing visible mets you ask yourself what you can do against these mets. If you then decide to wait 15 years for any survival evidence and start with ADT only, this means putting the PSMA PET/CT result into the bin. You do not need it.

There are many studies which all show that local therapies against these mets are beneficial for many patients. These studies are no randomized studies with a long observation period to allow to determine a survival benefit. However, there is also no evidence at all that local therapies against mets will have no survival benefit.

If your PSA value is rising and you see mets on your PET/CT scan you have to decide what to do right now. The currently available studies can serve as an indication what you could do. I mentioned some of these studies in this post: www.healingwell.com/community/default.aspx?f=35&m=3839928&g=3840607#m3840607

I had my lymph node mets radiated with SBRT and will continue with radiating new mets when they appear. If local therapies cannot control the mets any more I will start with ADT. This is similar to the concept of the ORIOLE study Allen mentioned above. Or the STOMP study done in Belgium.

George

TA and George

To me it seems that if one has isolated mets which (by definition) are big enough to be seen with these CT pet scans, killing them with SBRT should slow down progression in the same way that killing the visible enemy coming through the line will slow down the advancement of the rest of the enemy at least for a time.
Is there no advantage in terms of additional life span to killing off the visible mets? Are you saying the micro mets are just as deadly so you need to carpet bomb all the mets with systemic therapy?
Bob

Allen
I hear you and forgive me for the simple analogy . Your analogy is more like a video game than a human enemy and surely more relevant. But my question remains: are all cancer cells equally deadly or are the visible ones more deadly because they're so large or voluminous ? Clearly the ones inside the prostate are the forbearers ( the queen bee) and that's why I elected to kill them via removal by RP. If it takes so long for prostate cancer cells to grow to the point they're deadly it would seem that killing them off as they surface should extend life. Have there actually been studies that prove that killing them off one by one has absolutely no impact on life span?
Bob

Allen said...
All I'm saying is that we do not have any reliable trials yet to support this, so the decision has to be made understanding the inherent uncertainty.

I fully agree with this. I did not write that there is a randomized trial which showed an extended survival. When I mentioned benefit I meant the benefit the particular study reported. This is not extended survival since the studies did not have a long observation period but some type of delay, e.g. the start of palliative ADT.

However, if you have to decide just now, you can make use of the reports of the available studies, knowing there is a lot of uncertainty now. All these studies indicate a possible delay of the disease.

Bob said...
Have there actually been studies that prove that killing them off one by one has absolutely no impact on life span?

No, absolutely not. There are just indications from small studies which almost all report that local therapies seem to delay the disease.

Bob said...
are all cancer cells equally deadly or are the visible ones more deadly because they're so large or voluminous?

Metastases need a certain size to cause death. They also have to grow where they can cause death. So micrometastases have to grow first before they can kill you. On the other hand ADT reduces bone density and increases the risk of cardiovascular events so a few people even die from its side effects.

My opinion is:
If you start with ADT, in a few years you will become castration-resistant and have to take Zytiga and Docetaxel. Zytiga got approved by the FDA since it showed to extend survival by 4 months, Docetaxel (10 cycles) showed 2.4 months.

It seems that you can delay the disease by almost two years before starting ADT as several small studies reported. This way you would gain much more than Zytiga or Docetaxel can offer later in the course of the disease. This with less toxicity, particularly in the case of SBRT.

George

George-

It may surprise you to know that, while it's rare, some men die of prostate cancer never having had detectable metastases. I have never seen a correlation between size of mets and mortality. In fact, some very deadly metastases can be quite small. My father died of one (in his brain) that was barely detectable.

Once again, you are just making up that there is any evidence that the disease is delayed by metastatic treatment. There is none. There are no studies, big or small, that show it delays progression at all, let alone by two years. You keep repeating this assertion - but there is no justification for it. If you want to act on your unwarranted conclusions, that's your right. And I do hope it works for you, although it's something one can never really know from his own individual experience.

Remember, it takes a median of 8 years from the time of biochemical failure after RP to the time the first met is detectable by a bone scan. The first mets are very slow to grow to the size where they become detectable by bone scans. By detecting them earlier with a PET scan instead, they have introduced significant lead time bias.

My plan based on what I believe to be effective is as follows and I'd love to have anyone shoot holes in it.

Depending on what my axumin scan finds I'll do the following:

1. If this scan finds no mets I'll just monitor via PSA tests and periodic scans.
2. If this scan or future scans find a few mets in places not previously radiated and which are not dangerous to radiate( like the spine) I'll subject those mets to SBRT.
3. If this scan or a future scan finds systemic mets or mets in prostate bed or pelvic lymph nodes which have already been subjected to IMRT, I'll start systemic therapy.

My goal is to not go back on ADT except as a last resort.
Bob

TA
Thanks; I'll look into it.
Bob

Bob-
All the ADT you've had so far is adjuvant ADT. Adjuvant ADT means that it is added to radiation therapy. Adjuvant ADT is usually started a few months before radiation (neoadjuvant), continued concurrent with radiation, and then continued afterwards. Some ROs continue it for up to 3 years afterwards. In other words, when you are using ADT as part of a strategy to cure prostate cancer, it is adjuvant.

Nothing you have done so far is anything like "delayed ADT" in that trial. Immediate or delayed ADT in that trial is something else entirely. It means that the ADT is a permanent part of life from that point onwards. It may be continuous or intermittent, but it will always be there. In that trial, "immediate" refers to permanent ADT started as soon as PSA begins to rise after the last attempt at curative salvage therapy. "Delayed" refers to waiting until some other benchmark occurs, like high PSA, quickly rising PSA, or detectable metastases.

I did not realize your PSA was doubling monthly.If your PSA is doubling monthly, I think that you are already beyond the point where early ADT is possible. I think most urologists would start any patient with monthly doubling PSA on lifelong ADT immediately. Your cancer is micrometastatic and systemic - the best way to slow it down is with ADT.

77% of the "immediate" arm, and 47% of the "delayed" arm mentioned adverse SEs of the ADT.That makes sense because many of the SEs of ADT get worse over time. However, there were no differences in "overall" assessment of quality of life. People get used to it and find a way of accommodating those SEs into their lives. We've seen this effect also in comparisons of intermittent ADT to continuous ADT. One would expect that men on continuous ADT would rate their overall QOL as worse, but that seldom happens - after one or two cycles, the assessment is usually the same. Most (3/4) of the men in this study used ADT intermittently.