Need advice on rampant metastasis.

[Sewinggam]

To catch folks up, my asymptomatic husband had a 9.71 psa in March. MRI in May confirmed spread. Biopsy inJune said Gleason 4+3 an 4+4. PSMA scan in July showed Mets in bones, lymph nodes, lungs and soft tissue of brain. Brain MRI confirmed 2 tumors.

Duke doc says he’s never seen so much Mets in new, asymptomatic patient.

Firmagon started immediately. Docetaxal started yesterday (7/12). Meet with neurosurgeon on Friday.

Guardant DNA blood test came back saying there was no cancer DNA shed in his blood (of any kind…not just ones they can identify). Doc says he’s never gotten this result back from a metastatic patient.

Questions -

Doc was going to add Zytiga or enzalutamide after chemo. He said there is no benefit doing all three (Firmagon, docetaxal and Zytiga or enzalutamide) at the same time. But I thought the triple therapy research recommended doing them together.

I am pushing for a tissue biopsy of another site than prostate to send to Foundation Medicine since the Guardant came back with no evidence of cancer DNA in bloodstream. Thoughts?

Has anyone else experienced a case like this - so much metastasis but no DNA info in blood? Guardant says the sample was perfect, just nothing there.

Anything else I should be thinking of or asking? I believe the doc said he is not a candidate for immunotherapy because of the lack of DNA shed.

Thank you!!!!

[6357axbz]

I didn’t see in your profile that you had the prostate eithe surgically removed or burnt out with RT. That’s very surprising.

[CAMPSOUPS in reply to 6357axbz]

Systemic, fully metastasized at the start. At the time of dx.Like me.

[Sewinggam in reply to 6357axbz]

Since at time of diagnosis it had already spread to brain, my understanding was they thought RP would just create more issues - lessen quality of life without necessarily prolonging it. I assume same with RT. But that may change once we meet with neurosurgeon. If he feels he can do something for my husband, that would change the picture.

[Tall_Allen]

I'm surprised that Duke isn't into triplet therapy. Andrew Armstrong is one of the top oncologists in the world. Email your MO the results of ARASENS and PEACE1 and discuss:

nejm.org/doi/full/10.1056/N...

sciencedirect.com/science/a...

I'm not big on the cell-free DNA blood tests like Guardant 360 because they depend on shedding cells from metastases, which can be variable. A biopsy of a recent large met is more reliable and you can learn more from it. While you are understandably curious about genomics, there is a LOT more to be learned.

(1)- histology - especially important with such an unusual presentation.

(2) IHC - the Wang lab at Duke is renowned for their collection of antibody stains. I would recommend these if there is sufficient tissue: AR (androgen receptor), PSA, PSMA, MSH2, MSH6, STEAP1, PD-L1, chromogranin A (CGA), neuron-specific enolase (NSE), synaptophysin (SYP), DLL-3, CD56, Somatostatin (SST).

(3) Any good tissue-based genomic study is fine- try to get more than one met if possible.

[kapakahi in reply to Tall_Allen]

TA, you are a prince among men.

[j-o-h-n in reply to kapakahi]

And what am I a ham sandwich?

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 07/14/2022 7:31 PM DST

[kapakahi in reply to j-o-h-n]

I was hoping people wouldn't take my comment that way -- not what I intended at all. You're included in the princes -- see my followup comment below where I said "Are these guys the greatest help you could want or what? Solid knowledge + hope = a lot to go on, proactively, exactly what you need right now."

If you're a ham sandwich, you're the awesomest, most delicious, most digestible and funniest ham sandwich that has ever existed in the history of the planet, solar system, galaxy, universe, and multiverses. Burp!

[j-o-h-n in reply to kapakahi]

What type of bread?

Good Luck, Good Health and Good Humor.

j-o-h-n Thursday 07/14/2022 7:56 PM DST

[CountryJoe in reply to j-o-h-n]

I wish I could meet you, my friend.

[j-o-h-n in reply to CountryJoe]

For laughs or gaffs?

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 07/15/2022 10:09 PM DST

[j-o-h-n in reply to CountryJoe]

See my new reply....

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 07/15/2022 11:20 PM DST

[SeosamhM in reply to Tall_Allen]

I'm not big on the cell-free DNA blood tests like Guardant 360. Agreed! Cell-free DNA (cfDNA) testing is a developing screening tool to be used in conjunction with others! Do doctors ever read the fundamental studies anymore before they spout nonsense to patients and caregivers? See:

ncbi.nlm.nih.gov/pmc/articl...

In this study, about 1 in 4 people with KNOWN metastasis had NO (testable) DNA alterations detected. Talk about experiential bias: Last time I checked, 25% is a pretty significant population size - just because this doctor has never seen a negative Guardant test in a confirmed cancer patient isn't because it is impossible. Quite the opposite.

My opinion? Any doctor that overuses the phrase "I haven't seen..." in their communications needs to be replaced with someone who HAS seen. No offense, doc, but you can learn from some other patient. Keep pushing, Sewinggam!

[Sewinggam in reply to SeosamhM]

Will do! Thank you!

[Sewinggam]

Thank you!!

[GP24]

Doc was going to add Zytiga or enzalutamide after chemo. He said there is no benefit doing all three (Firmagon, docetaxal and Zytiga or enzalutamide) at the same time. But I thought the triple therapy research recommended doing them together.

Firmagon and Docetaxel cause significant side effects. I would add Zytiga or Enzalutamide after the Chemo is finished. A number of patients in the PEACE-1 trial were treated this way and this was called triplet therapy too.

[Sewinggam in reply to GP24]

Thank you!

[rsgdmd in reply to Sewinggam]

My treatment plan was for triple therapy - Lupron, abiraterone (Zytiga) & docetaxel. A couple weeks after Lupron injection, started abiraterone (& 5mg prednisone). Four days later developed irreg. heartbeat so stopped. Irreg. heartbeat lasted for 4 days. Got clearance from cardiologist & restarted abiraterone. First day had irregularities & then OK. Bloodwork immediately prior to 1st chemo showed significant rise in bilirubin after 6 days on abiraterone. So, I'm off abiraterone til after chemo & will then try to restart with 1/2 dose at first. Was told ideal is all three at same time, but not unusual to have to stop abiraterone.

[Sewinggam in reply to rsgdmd]

Thank you!

[LearnAll]

With such low PSA and so many mets indicates that it is not a regular, garden variety PCa. Sad to say that it appears an Aggressive Variants and deserves aggressive testing and treatment. Biomarkers for Neuroendocrine variant is certainly needed. LDH, Chromogranin A, Synaptophysin and Neuron specific Enolase should be tested ASAP. If NE variant is established, platinum based chemo needs to considered sooner than later. Because if regular cancer cells are suppressed/killed aggressively, that stimulates Neuro Endocrine cells to multiply faster.

[Sewinggam in reply to LearnAll]

Yikes! Chromogranin A came back normal. Do we need all the others as well to rule out neuroendocrine?

[LearnAll in reply to Sewinggam]

Chromogranin A coming normal is good. Just ask for LDH (lactate dehydrogenase) LDH is a biomarker for tissue damage and increase in aggressive variants.

Also ask if he has OSTEOLYTIC type lesions on bones or only OSTEOBLASTIC ones.

Osteolytic lesions occur in aggressive variants and have high risk of fractures.

[Sewinggam]

Got it. Thank you!

[kapakahi]

Are these guys the greatest help you could want or what? Solid knowledge + hope = a lot to go on, proactively, exactly what you need right now.

[Sewinggam in reply to kapakahi]

Yes!

[nobaday]

Asymptomatic. No pain, good QOL despite lots of Mets? My PSA remains low <0.1 with slow growing spinal Mets . I thought I had aggressive cancer . I tested negative for neoendocrine. Aggressive cancer but I’m nearing the 5 year mark and I am expecting a few more years!! I just need surgery when cancer pushes against spine ( Nov 2017) or erodes C3 ( June 2022). Lu177 is probably next for me to If in your position I would look at Lu177 to zap Mets … after a couple of rounds of chemo to qualify for it.

[Sewinggam in reply to nobaday]

Thank you!