Positive Guardant 360 Test-What does it mean

[Schwah]

I was Gleason 8. Seven years after a focal city procedure my PSA began t rise and they found 3 mets on rib and pelvis. I did SBRT Lupron/Zytega and 4 rounds of Taxotere. After 21 months of of the Lupron /Zytega and .01 PSA, I went on an 18 month “vacation” from Lupron/Zytega. With my PSA rising again, my most recent PSMA scan revealed a “probable met” at L-5. I will be hitting that met with SBRT and re starting systemic treatment. My MO also had me do a Guardant 360 blood test. Of the results he said:

“There is measurable cell-free DNA from your tumor floating in your blood that we can quantify and track to see if your cancer cells are being impacted by the treatment.”

I replied:

“That can’t be good for my prognosis/having cancer in my blood stream”

He replied:

“This is not cancer cells. This is cancer DNA that leaks out of the cancer cells. This technology can detect extremely miniscule amounts of DNA and it can be quantified accurately so we can evaluate the efficacy of treatment. There is a mutation, that is how we know it is cancer DNA. It may be a mutation that responds to Olaparib but that is not sure because it is a “one-off” type of mutation that has not been seen before.”

I also am waiting to get the results of my CTC test which I assume will be positive too?

Anyone smarter than I want to take a stab at explaining what the positive Guardant 360 test means, how it might impact my treatment and prognosis? Also how the CTC results impact all that ? Thanks in advance.

Schwah

[GP24]

With a Gleason 8 and having had mets this is a result you should expect. You will have tumor cells or their cell-free DNA circulating in your blood. It will take a long time until these cause metastases. You can check if the amount of CTCs or cell-free DNA decreases after your next treatment. Or you use the mutations of these cells to see if you qualify for Olaparib.

I think the prognosis is determined by your next treatments and not so much by cell tests.

[6357axbz]

In retrospect was your ADT holiday worth it?

[Schwah in reply to 6357axbz]

I’d say yes. Especially since I was able to use the PSMA scan to monitor my disease. It apparently saw this much sooner than conventional imaging would have done.

Schwah

[6357axbz in reply to Schwah]

I suppose one big question still is whether it (intermittence) postpones or accelerates the onset of resistance.

[Schwah in reply to 6357axbz]

Studies so far have been inconclusive when comparing IADT TO CADT. BUt those studies were done before the use of Zytega with ADT and with much shorter duration f the “on” time. I did 21 months plus radiation to my mets plus 4 rounds Taxotere. I was also ogliometastatic with a PSA that never exceeded 10

Schwah

[Fanger1]

Please go to Biocept. com for more info/literature links on CTC testing.

[6357axbz]

Here’s a link re a phase 3 clinical trial concerning CTCs medpagetoday.com/meetingcov...

[Schwah in reply to 6357axbz]

Very informative article. Thank you. It sounds like the CTC test is a much more important test in terms of survival in the guardant 360 test. I did the CTC test three years ago and it was negative. We shall see what it is this time in the next week or so. Schwah

[JPnSD in reply to 6357axbz]

Thanks for this info very helpful. Having just joined SWOG's Patient Advocate Committee, I am pleased to see their hand in this work.

[GP24]

Agreed, cell-free DNA will not cause metastases. I assumed that if there is circulating cell-free DNA, usually there are circulating tumor cells too.

[Tall_Allen]

1) The advantage of Guardant 360 is also its disadvantage. It tells you that some cells somewhere had that cancerous mutation (did he say which mutation?) But it doesn't tell you where it came from. I assume it didn't show up in a germline test. It may have come from the tumor you will be having SBRT on, or it may be from somewhere else too small for any PET scan. As metastases progress, genomic breakdown continues, and there may be many cancer cells that haven't been picked up in the cfDNA test.

I think in your case, where there is only one detectable met, a tumor tissue biopsy would be more informative.

2) CTC> 5 per 7.5 ml is prognostic

3) So far, PARP inhibitors have a strong effect on just a few of the more common BRCA2 mutations. They may have some less pronounced effect on other fairly common mutations. But their effect on rare mutations is unknown because we don't have enough patient data. Unfortunately, PARP inhibitors are highly toxic, so it isn't just something you'd want to try out.

[Schwah in reply to Tall_Allen]

He said “it is a “one-off” type of mutation that has not been seen before.” Since the lesion was so small and they were only 90% positive it was even a met, I looked into a biopsy to both confirm the met and And hopefully get enough tissue for testing. The UCLA Doctor Who does those biopsies was honest enough to tell me that with the small size there was a good chance they would not be able to confirm the met and even if they did it was highly unlikely they would have enough material to send for testing. With my PSA rising, even if the biopsy found nothing, I planned on doing the same treatment because it was likely they would have just missed it. Since the biopsy result would not change my treatment and was highly unlikely to get it enough material to test, I saw no reason to do the biopsy.

Schwah

[Tall_Allen in reply to Schwah]

Yes, that's a problem with small metastases, but it's good that your metastases are small or invisible. There are many, many mutations that can happen. If Guardant 360 tests for it, it must be in a gene that they've found to be active or deleted in prostate cancer. Too bad it's not one of the few actionable ones. Maybe someday it will be.

[mrscruffy]

Nalakrats, funny you should mention the Ashkenazi Jews. My Mexican born grandfather swore up and down his father was a New York Jew, we wrote it off as the ramblings of an old man. Did our family genetics and damn if he wasn't telling the truth. Helps to explain BRCA2

[keepinon]

Just curious. In the 2nd to last paragraph you said you would want to avoid resistance if you can. How do you avoid resistance if you need to go back on ADT?Just by cycling off and on?

Thanks for your time!

[CalBear74]

Ashkenazi membership means high IQ. So you were the smart ass in school Nal?

[Schwah]

So no second line ADT drugs for you Nal. That means no Zytega, no Xandi etc etc ? So with all due respect, how do you reconcile that position with the Lattitude and Stampede studies showing adding of those drugs early to ADT increased survival some 40%? Trust me when I say that I am always willing to “question the experts”. But I’m not clear on what the question is. Is it that you do not believe those studies, or believe that they are flawed in some way? Or that you believe you’ve found a way with other supplements and off label treatments, to extend life beyond what that combo can deliver? And your MO concurs? Please don’t take offense. I (and I am sure others here) do not fully understand your thinking but I am open to other points of view. I just need to be able to follow the logic.

Schwah

[6357axbz]

Did you get CTC results yet?

[Schwah]

Yes. Not exactly sure what this means. Do you ? Everyone says it’s a 0-5 scale but not sure if this is a zero ?

Schwah

[6357axbz in reply to Schwah]

I don’t know what your showing me. My CTC results taken at MD Anderson look like this:

CTC

Your Value

None Seen Cells

Standard Range

Cells

Reference Range: Breast = < 5 CTC

Prostate = < 5 CTC

Colorectal = < 3 CTC

Patients on Doxorubicin therapy, allow at least 7 days following dosage before blood draw. Patient samples with high levels of Doxorubicin may cause aberrant staining of leukocytes as cytokeratin and CD45 dual positive cells.

Analytical Method:

Immunomagnetic CTC Selection and Enumeration

Method Platform:

CellSearch CELLTRACKS AUTOPREP System

CTC Path Int

Your Value

No CTC was identified in a total of 30 images.

[Schwah in reply to 6357axbz]

So I cut and pasted your results and sent them to my UCLA MO and asked her why my report didn’t provide a 0-5 scale of circulating tumor that is supposedly very predictive of prognosis. She replied :

“There are various different CTC platforms. MD Anderson might have their own internal one so the report that is generated is different. What I take from your results is that at this time point, I do not see any targetable mutation that can help us determine choosing one medication over another. We know you have circulating tumor cells by just seeing your PSA rising.I am sorry you are not seeing something more/different in those reports.”

I’d really like to get something similar to what you got. I’ve looked online and the only one I could find was this one at Mayo:

mayocliniclabs.com/articles...

I called the number tho and they said they no longer offer it. Argh.

Anyway, I’d really appreciate it if you could inquire thru MD Anderson if there’s anyway to get that test (or a similar one) out here in souther California? Thx 6357.

Schwah.

[6357axbz in reply to Schwah]

In the link I provided that discussed the Phase III results about CTCs, presented by Amir Goldkorn, It states,

“In this exclusive MedPage Today video, lead researcher Amir Goldkorn, MD, of the Keck School of Medicine and Norris Comprehensive Cancer Center at the University of Southern California, explains that the results suggest that CTC count could be used as a noninvasive biomarker to help guide treatment decisions.”

Could you get an FDA-cleared CELLSEARCH platform CTC test there (USC) with an order from your MO?

I’m also a bit suspect of your MOs knowledge about CTC testing. She states that there are “various different CTC platforms”. However there apparently is only one FDA approved test.

[6357axbz in reply to Schwah]

Schwah, Any luck scheduling a CELLSEARCH platform CTC test at USC? You could also call Cellsearch direct at 18778374339. I would think they could tell you who else in your area is administering this test.

[Schwah]

I definitely plan on doing that. Right now I’m focused on my current treatment plan. I get my first infusion of Provenge on Monday and also start Monday on three straight days of radiation to my one met on L-5. I looked carefully at the Provenge studies and the evidence seems to indicate that the sooner it’s used and the lower your PSA at the tune used, the better the results. For example the major double blind study of Provenge showed on a 4 month median improvement in life expectancy. However, a further breakdown by PSA showed the lower the PSA the better the results. The lowest they looked at was under 22. For those men the advantage was over 14 months. I’m at 5 PSA. We shall see how it works.

As I looked at all the stats, I began to think about the way the studies our report it. They always talk about the median life expectancy. What they don’t show is the people that had their life expectancy extended many years. Because that doesn’t change the median. Those outliers should be an important part of the equation. I plan on posting about this soon.

Thx fir the info on the testing.

Schwah

[6357axbz in reply to Schwah]

Do you have one of those genetic abnormalities that result in Provenge being more effective?

[Schwah]

I do not. I was not aware of anyone claiming that Provenge worked better with certain abnormalities. I do have a lower PSA (5.1) and I am supposedly still hormone sensitive. So earlier in my disease which seems to have better results with Provenge. I am adding SBRT TO MY ONE MET and going back on ADT for at least another 6 months which supposedly both have a synergetic impact with Provenge. I may also add a little Yervoy to the mix which should further assist the Provenge. Not sure tho as the Yervoy side affects can be brutal n some cases. Schwah.

[6357axbz in reply to Schwah]

I’m probable wrong about the abnormalities...

[spencoid2]

me too, Jewish and smart assed. When I had my DNA tests they only tested for PC stuff. I was hoping to find out that I was at least 50% Poodle but no they did not test for that.