Lymph node dissection and oligometastatic disease

Hi All,

I have been at a difficult cross roads with how to proceed with my oligometastatic disease.

With not a huge amount of data available and hearing differing opinions from oncologists and on this site it's hard to really know what to do.

I recently went to see Dr. Karnes at the Mayo Clinic for his opinion and some clarity and direction.

Dr. Karnes regularly performs surgery for oligometastatic disease including lymph node dissection and prostatectomies. He also regularly performs salvage prostatectomies on previously radiated prostates.

As I had previously been treated with radiation, a salvage prostatectomy was a particularly scary thought considering the high rate of negative side effects it carries, including a 25% rate of total incontinence.

Luckily a biopsy just revealed no local disease in the prostate or seminal vesicles and a prostatectomy is not necessary. Would I choose a prostatectomy if I had disease? That consideration has been consuming my thoughts lately and as some evidence does suggest removal of any disease has potential survival benefit, I was heavily considering it.

I am going to proceed with the lymph node dissection as a Gallium scan I had done a few months ago shows clearly active disease. Hopefully my PSA will drop like a stone afterwards.

Tall Allen, you had suggested asking Dr. Karnes for any documented proof of the benefit of treating oligometststic disease. He shared this with me which supports the practice of treatment.

http://meetinglibrary.asco.org/record/50695/edbook

This is present in a segment tilted "surgery with the presence of distant metastatic disease"

"Another study compared 23 patients with low-volume M1b disease (three or fewer skeletal lesions) who underwent radical prostatectomy/ePLND with 38 controls treated with ADT alone.29 Cytoreductive radical prostatectomy was associated with longer time to castration resistance (40 vs. 29 months), improved clinical progression-free survival (PFS) (39 vs. 28 months), and improved CSS (96% vs. 84%)"

Though I am not such a patient I find it compelling that performing a prostatectomy and lymph node dissection on patients with distant skeletal lesions actually showed some survival benefit. Though the benefit is not extremely profound, ANY benefit in this setting is hard to ignore as it shows that removing any cancer is positive for survival.

Whether the stress and trial of going through a tough treatment is worth the amount of benefit it offers is truly daunting and my heart goes out to anybody that has to wrestle with these decisions.

I know there is ongoing debate over the benefit of local treatment of oligometastatic patients but if the data in this literature is accurate it's pretty convincing to me there is true benefit.

Here is another link with similar content.

https://am.asco.org/treating-oligometastatic-disease-prostate-cancer

This sentence has been haunting me and definitely motivational in seeking aggressive treatment. Ouch.....

“In all of the phase III studies, OPC patients with a low tumor burden treated only with androgen deprivation therapy [ADT], have a median overall survival [OS] of about 7 years.”

I didn't realize this was really my situation. It's tough to read such things.

Yarbo3-

I know this has been a very difficult decision, and a greatly admire your questioning attitude. I am also relieved that your prostate is no longer at issue - congratulations on that.

The language here gets in the way of understanding this issue. "Oligometastatic disease" may be used to refer to two different situations:
(1) presence of 3 or fewer metastases when the prostate is still present
(2) presence of 3 or fewer metastases when the prostate has been taken out of the picture with surgery or radiation.

And to complicate it still further, there are subtypes for both - when the metastases are only in the pelvic lymph nodes (N1), but not distant (M0). Other subtypes are N1M1 (both local and distant mets), and N0M1 (distant only).

Situation 1 may be treated by "debulking" of the prostate - the mothership of most of the metastases. Situation 2 may be treated with "metastasis-directed therapy" (e.g., ePLND only, LN radiation, bone met ablation, etc.)

So whereas you are in situation (2) with N1, the quote Karnes gave you is for situation (1) with M1 subtype - a very different situation. The evidence for eliminating the prostate (while scant) is more compelling than the evidence for metastasis-directed therapy.

The other impediment to understanding the issues is the confusion caused by the term "local control." There is no question that metastasis-directed therapy provides excellent local control - when those metastases that are eliminated by ePLND or nodal radiation are removed, they are removed for good. 90+% local control is not uncommon. The question is - does "local control" serve any purpose when there are thousands cancer cells in systemic circulation. In other words, does local control affect survival at all? That is the question that has no answer - nothing Karnes told you or can tell you addresses that question because it can only be answered with a prospective randomized clinical trial. That has not happened yet. The only evidence we have are some retrospective matched-case analyses, and they arrive at mixed conclusions. You can read about them here:

Unwarranted conclusions about oligometastatic treatment

This is a tremendously difficult decision because there is no clear benefit and there are distinct risks from ePLND. It is those risks I would be most focussed on - what is Karnes record with regard to lymphoceles and lymphedema? What is the RO's record for late-term bowel toxicity?

Perhaps it may help to know that survival is much longer among men whose metastases are discovered in the lymph nodes rather than the bones. New LN mets are slow to arise in the beginning (this is what complicates the issue of whether there is any treatment benefit). Also, survival has been lengthened by new systemic therapies. Whether you decide to treat locally or not, I think the new data on early use of systemic treatment with Zytiga is worth your consideration.

Yarbo3 said...
What I don't understand is why, if there is no rise in PSA going on, would those cells be considered evolving disease which would discredit local treatment?

PSA is a protein that gets released into the serum by tumors that typically develop a leaky blood supply. That kind of vascular growth is a common characteristic of all solid tumors. Blood cancers, like leukemia for example, do not develop their own blood supply. So cancer cells in systemic circulation, and there are thousands at any one time, may not contribute at all to PSA. Even some prostate cancer tumors do not put out detectable amounts of PSA. PSA is a good biomarker of progression, but it is not the only one. And it's not at all clear that eliminating a few tumors that are generating serum PSA eliminates progression.

Yarbo3 said...
Does it ever happen that prostate cancer cells are not becoming metastatic sites yet are becoming castrate resistant?

Absolutely. There is a setting called non-metastatic castration-resistant prostate cancer. It's not common, but it's there. Scott Tagawa's trial of Lu-177-PSMA is targeted to that population of patients. He wanted to develop it as a systemic treatment for those who have systemic micrometastases and have advanced to castration resistance without any detectable metastases.

Thank you everyone for this very educational discussion.

TAll Allen, you wrote,"Perhaps it may help to know that survival is much longer among men whose metastases are discovered in the lymph nodes rather than the bones."
Is this because the lymph nodes are invaded earlier than the bones so the disease is not so andvanced? Or does the cancer sometimes bypass the nodes and go directly to the bones?

Thank you for the description of PSA. A question please.... What can we understand (if anything) about the nature or source of the cancer if the PSADT is short vs long?

YARBO3 said...
If we can assume this is accurate how can I possibly not see survival advantage in reducing oligometastatic tumor burden?

Allen, how do you feel about that paragraph? Is this not close enough to clinical data to find conclusive? Do you find it suspect?

Once again, those men were in a completely different situation from you - they still had their prostates. They had prostate-directed therapy, not just metastasis-directed therapy. Although there is a small amount of met-to-met seeding, almost all one's mets came from the prostate itself. The prostate is the motherlode of metastases and progenitor cells - almost all come from there and continue to come from there. Shutting off that firehouse may make a difference. It is much less likely that shutting off the trickle of mets from other mets may make a difference. There are a lot of mets floating around with or without them.

Annie88 said...
Is this because the lymph nodes are invaded earlier than the bones so the disease is not so advanced? Or does the cancer sometimes bypass the nodes and go directly to the bones?

In STAMPEDE, for example, 44% were newly diagnosed w/ bone mets and w/o LN mets, 28% were newly diagnosed w/ LN mets and w/o bone mets. Among those diagnosed with either, but not both, survival is much longer among those with LN mets only. But remember that it is much harder to diagnose LN mets definitively. So it is quite possible that cancer has been undetectable in the LNs for even longer. That would mean LN-only cancer survival is even longer than we know.

George and TA,

Thank you for answering my question about bone and LN mets. I had no knowledge of what you explained to me. Gosh, I never thought I'd see the day where my husband's N+ status could possibly be a good thing. I guess it's all relative.

Still, not much good news of any type coming our way these day, so thank you!

Well if anyone can get a good yield out of it, Karnes can. I hope he finds a lot of those suckers.

Yarbo,

We've met with Dr. Karnes and felt the same way about him. I didn't know that Mayo models itself after socialized medicine. I can tell you that in terms of quality and wait times, it manages to do a heck of a lot better than the socialized medicine I know of!

It's important to feel good about your plan of care. I wish you well and please let us know how it goes.