Dr Kwon on Imaging For Recurrence

Pratoman-

I think Garyi's case provides a good case study about why a positive margin, or in his case, a PET-detected tumor outside the prostate (together with no PET-detected tumors beyond the prostate region), actually increases confidence that SRT will be successful. Of course, he can't just treat what he can see, but he has a higher probability that prostate bed treatment will be successful. He can't be 100% sure that all the remaining cancer is in the prostate bed, but the probability is increased.

If, on the other hand, he had been unable to find any cancer with the PET scan, then micrometastases, which could be anywhere, may have been the cause of rising PSA, and I think he would have been more aggressive in his approach. But he would have less assurance of success.

That's exactly my point -- knowing that there is a tumor increases confidence in SRT success. I don't remember everything that Kwon said, and can't comment. If you're saying that Mayo has seen a couple of men with low post-prostatectomy PSA who nevertheless evince metastases, that's very rare, but I'm sure there have been such cases. Some very rare mets, as with small cell prostate cancer, put out no PSA. As I said, his Youtube video is his opinion and doesn't include any real statistical evidence, only anecdotes. If he had any statistically valid evidence, he would certainly publish it in a peer-reviewed journal. If what is confusing you is trying to jibe what he said with valid statistical evidence to the contrary, I'd go with the evidence. As I said, I believe this video does patients a disservice.

Thanks for clarifying.

Yes, that's a big problem with relying on the "gee whiz" anecdotes to inform decision making. As I said, mets will sometimes show up if PSA is very rapidly rising. He selected the outliers to present, not the average patient.

Mayo does NOT have a very good PET scan, unless they've since switched to one of the better ones than the C11 Choline PET/CT. They certainly did not have one in 2014 when that video was made. Garyi got the best of the ones now in clinical trials, and his PSA is within the range that DCFPyL PET might detect it - yours is not. And you can't wait until mets are PET-detectable -- that would be a self-fulfilling prophecy. You don't seem to want to acknowledge how curable a PSA recurrence is, even with no positive margins, as long as it's treated early enough. Your assertion that your recurrence, if you have one, is already metastatic is quite frankly ridiculous.

As I recall, almost all of his selected gee-whiz slides were men who were followed for only 2 years after having very few (oligometastatic) mets. Two years is nothing. Prostate cancer metastatic development is almost always very slow at first. It's not uncommon for two or more years to pass without any new mets, even without zapping what is there. That's why the video is so deceptive - it doesn't show you the control group - what would have happened with no treatment.

If you want to understand just how misleading that video is, read this:
/pcnrv.blogspot.com/2017/05/unwarranted-conclusions-about.html

We cannot draw any valid conclusions about whether there is any survival benefit at all to metastasis-directed therapy until an RCT in the UK has data in 2021. Local radiographic control and PSA reduction are expected, but they are not useful endpoints.

Gear, thanks for that link, and TA, thanks for writing it, very helpful.

TA, thanks for the link as well. Re your comment "...Your assertion that your recurrence, if you have one, is already metastatic is quite frankly ridiculous.", i dont remember saying it was metastatic, i said i would hate to radiate the prostate bed then find out it was metastatic"

I am sending you an email, just to clarify.

George said...
The randomized STOMP trial (NCT01558427) will be published soon. Apparently they found that the group which got metastasis-directed therapy showed a median 21 months till progression while the control group (active surveillance) showed 13 months to progression.

It would be nice to be able to avoid 8 months of ADT. If because ADT was not begun at the first sign of metastases, which is the standard of care, life is shortened, then it would not be nice to avoid. In most trials, a new therapy is compared to standard of care. In STOMP, the control group is not getting the standard of care, which would be ADT. Unfortunately, progression-free survival is not an adequate surrogate endpoint for overall survival.

As I wrote in reviewing a short-term metastasis-directed study at Johns Hopkins:

"There is no doubt that local control will be excellent, but stopping the progression of 1-3 metastases does not necessarily mean that the cancer has been slowed down systemically at all. Certainly, PSA will fall as an immediate result of treatment. For those who are used to monitoring PSA as a measure of their cancer's systemic progression, this can be confusing. It's worth taking a moment to recall what serum PSA comes from in detectably metastatic disease. PSA is a protein on the surface of prostate cancer cells (and healthy prostate cells too.) It doesn't leak out into the blood from prostate cancer unless a tumor forms with its own blood supply. Tumor blood supply tends to be leaky, and so PSA is detected in the blood serum. Larger tumors with more blood supply put out more PSA. So irradiating those tumors and shrinking them is likely to eliminate the PSA they put out. But what about the micrometastases that do not yet have appreciable blood vessels? If there are thousands of them, will it matter that serum PSA was reduced for 6 months? No one knows the answer to that question and this Phase 2 study will not provide the answer."

/pcnrv.blogspot.com/2017/07/first-us-randomized-clinical-trial-of.html

anb-
I think you are confusing "out-of-the-box" thinkers with publicity. Just because one publicizes what he is working on while the other pursues his hypotheses quietly does not mean they are any the less "out of the box." Usually, the miraculous breakthroughs require years of plodding research, as they did with all of the prostate cancer medicines in use or in test today. Sometimes, they just require a willingness to try something untested. I just got a very interesting email from a patient of Howard Scher's today who is working through an innovative approach to hormone therapy. I've found that most medical oncologists at teaching hospitals are willing to try new ideas. They know they don't have the answers. But few publicize their case studies until they are ready for peer review. Peer review can sometimes help weed out the quackery. It's not fool proof, but it helps, i think.

In the US, a few illustrious names come to mind - Howard Scher at MSKCC, Emmanuel Antonarakis at Johns Hopkins, Chris Logothetis at MDAnderson, Celestia Higano at UW Seattle, and Oliver Sartor at Tulane. There are others.But if innovative, "out of the box" approaches are what you are looking for, they have been responsible for many of the top breakthroughs.

As I wrote to you, they have discovered excellent biomarkers for at least one kind of checkpoint blocker -- the new indication for Keytruda. One HWer was discovered to have that biomarker and is doing great on Keytruda now.

In response to George's question, ONC (Petrylak) said he was starting with Degarelix to avoid testosterone flare.

To Tall Allen: I'm trying to get to Scher. Since I had previously seen someone at MSKCC they said I had to start there. Because of her speaking commitments and other scheduling took around six weeks to get an appointment, which will be in about 10 days.

Plan to pursue Antonarkis, especially since he is close to Bethesda, MD where NIH is. Sounds like at a minimum I should also pursue Logothesis.

One reason I've been delaying is that if I do get a prostatectomy they will be able to biopsy a fresh specimen, which I understand will be more informative than the biopsy done Jan 2017.

Also want to do Provenge. NIH researcher in charge of study I'm in (Madan) recommended it and said "with immuno the earlier the better". Petrylak seems to have a decided preference for sequencing treatments.

Biomarkers are definitely something I want to pursue.

Responding to an earlier comment in this thread that expressed confidence Mayo would not try to drum up business, I submitted to Kwon the results of my Combidex scan which showed eight mets in the para-aorta and common iliac regions. We exchanged comments, but he refused to say anything about whether he thought my situation was suitable for his techniques UNTIL I CAME FOR A C-11 SCAN. I told him I was quite happy to go for his scan, but only if he could say that if his scan was similar to the Combidex then his techniques could be applied. No dice. Also, Mayo says without qualification that Medicare will cover the C-11, but there are forum reports of rejections as well as successes.

Great thread thank you guys!

Everyone have a great 2018

Charley