Newly-discovered Micro-Mets: What wo... - Advanced Prostate...

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Newly-discovered Micro-Mets: What would you do?

SeattleDan profile image
42 Replies

Recent (my first) PSMA Pylarify scan shows I've acquired 9-10 tiny lymph node metastases scattered in the common iliac, mediastinal, and left supraclavicular regions of my body. I'm still hormone-sensitive, but would prefer not to go back on ADT if possible (history of heart concerns). Area radiation oncologist and Cyberknife expert I trust is open to going off-standard of care with Cyberknife 'spot welding' on all these spots to see if I gain progression-free time (he has experience doing this). My current 2.7 PSA has increased quite slowly in last untreated 5 years (post surgery, external beam, & year on Lupron/Apalutamide). Gleason- intermediate 7.

I could 1) watch closely a while longer, 2) do a period of standard of care ADT now, 3) try Cyberknife 'spot welding' on all spots to see what happens, or 4) do both Cyberknife and ADT now.

What do you think, guys?

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SeattleDan profile image
SeattleDan
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42 Replies
Tall_Allen profile image
Tall_Allen

It is a common error to think that PSA=prostate cancer. Among people (patients, as well as doctors who should know better) who make that error, "progression-free" usually means that PSA doesn't go up, at least for a while. They make the mistake of thinking that if PSA is not "progressing" then the cancer is not progressing. You can read more about this error here:

prostatecancer.news/2020/07...

While some hypothesize that metastasis-directed-therapy in the oligometastatic setting may have some benefit, there is no one who seriously thinks that playing whack-a-mole when there are 9-10 metastases has any benefit.

The only way to delay progression when the cancer is systemic is using systemic therapy. GnRH antagonists (Firmagon, Orgovyx) and orchiectomy have fewer cardiac side effects than GnRH agonists (like Lupron).

I sug

SeattleDan profile image
SeattleDan in reply to Tall_Allen

Thank you so much, Allen. I will try to give your article and considerable research some thoughtful attention.

SeattleDan profile image
SeattleDan in reply to SeattleDan

Did you start to say a bit more and get interrupted? "I sug"...

Tall_Allen profile image
Tall_Allen in reply to SeattleDan

I probably had a senior moment :-)

dhccpa profile image
dhccpa in reply to Tall_Allen

Great post. TA. I think this point needs to be hammered home more. I still see the error you mention said over and over on all forums.

Fiddler2004 profile image
Fiddler2004 in reply to Tall_Allen

Amazing article... thank you for sharing

cigafred profile image
cigafred

As a sample of one, I had IMRT to my eight metastases (4 to 9 mm) in the common iliac and para-aortic areas, along with three months of degarelix. After the ADT wore off PSA returned to its prior levels. So not much benefit? Maybe, but I am undetectable now, six years later, while on first-line ADT all along.

E2-Guy profile image
E2-Guy in reply to cigafred

I made the mistake of having 8 sacral LNs surgically removed after they were identified via a 68Ga-PSMA PET CT scan which simply lowered my PSA for about 9 months. I wish I had corresponded with TA prior to subjecting myself to this expensive, time consuming and worthless venture! I Flew from my comfortable Thai nest down to Melbourne, AU, back to Thailand, then to CA where the surgery was performed, and back to Thailand. After all of that I started applying tE2 gel which has kept my PSA at undetectable levels for almost four years.

I am a bit confused about TA's post above regarding PCa and PSA levels? "They make the mistake of thinking that if PSA is not "progressing" then the cancer is not progressing."

patscancer profile image
patscancer in reply to E2-Guy

What is t2E gel?

E2-Guy profile image
E2-Guy in reply to patscancer

'Transdermal Estradiol' gel that enters the blood trough the skin. It is basically the same as 'The Patch', except that you simply rub it on your skin instead of wearing a patch...another form of ADT.

Graham49 profile image
Graham49 in reply to E2-Guy

If that surgery set your cancer back 9 months, I don't think the treatment was totally worthless. It reduced the volume of your cancer. With a smaller volume it will take longer (maybe never within your lifetime?) for mutated castration resistant cells to build up to a significant level.

dhccpa profile image
dhccpa in reply to cigafred

That confused me. You stopped degarelix after 3 months but have stayed on ADT the last six years? You switched to a different ADT? Or is degarelix not considered ADT by some? Thanks.

cigafred profile image
cigafred in reply to dhccpa

Yes, switched from degarelix to lupron, and then eligard.

dhccpa profile image
dhccpa in reply to cigafred

Ok thanks

GP24 profile image
GP24

There are no trials yet which have completed and shown that removing the mets provides a survival benefit. However, as a patient you usually prefer to remove the mets than to keep them for later. Here is a trial which will radiate up to ten affected lymph nodes:

bmccancer.biomedcentral.com...

I would get the mets radiated and combine that with six months of ADT.

SeattleDan profile image
SeattleDan in reply to GP24

Thanks- I did hear word of this. Unfortunately it looks like it's not being optioned in any US locations (Seattle is pretty close to Victoria, BC however..)

GP24 profile image
GP24 in reply to SeattleDan

You may watch this video about radiating oligometastases. Dr. Palma is the primary investigator of the Comet-10 trial.

podcasts.apple.com/us/podca...

tango65 profile image
tango65

If financially possible, I would look for a place abroad (Europe, India, Israel etc) to get Lu 177 PSMA treatment which is a systemic treatment and it has shown to prolong life. I would start ADT and then try to get the Lu 177 PSMA treatment.

SeattleDan profile image
SeattleDan in reply to tango65

Thank you. Definitely seems like something to consider.

tango65 profile image
tango65 in reply to SeattleDan

There are many places abroad. For hormone sensitive cancer I think it is possible to get the treatment in India and in Austria:

researchgate.net/profile/Ma...

markus.hartenbach@meduniwien.ac.at

fmri.in/doctors-profile/ish...

The trials for mHSPC, I believe are randomized trials for Lu177 PSMA vs SOC.

timotur profile image
timotur

Just my opinion, but if your mets are only to LN's, I would try Docetaxel six sessions with concurrent Zytiga/Lupron for six months. Given you had a heart attack on Lupron, I would get a baseline EKG and ask your cardiologist to check the Q-T interval which is known to lengthen under ADT. Then recheck it after three months to make sure you are not at risk of an arrhythmia or other heart complications that led to your heart attack. You may think about time-dosing Lupron, i.e. one monthly dose ever six weeks to lower the serum concentration (I did this and effectively kept T < 12 for 18 months).

GP24 profile image
GP24 in reply to timotur

No, Timotur, it works a bit better on lymph node mets. He could join the PSMAddition trial to get the Lu177 therapy.

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/show...

timotur profile image
timotur in reply to GP24

Thanks GP24, I remembered it wrong and edited that out! Still I would do Docetaxel/ADT before Lu 177.

SeattleDan profile image
SeattleDan in reply to timotur

Why would you prefer Docetaxel to Lu177? Just because already approved and what served you well?

timotur profile image
timotur in reply to SeattleDan

IMO, the best long-term remission would be with Docetaxel/Abiraterone/ADT per the PEACE trial. Lu-177 studies are forthcoming, but there is some positive data on early use.

tango65 profile image
tango65 in reply to timotur

Lu 177 PSMA has been shown to be more effective than chemo with cabazitaxel.

timotur profile image
timotur in reply to tango65

Is that Cabazataxel alone? Is Lu 177 better than Docetaxel/Abi/ADT per PEACE/STAmPEDE.

tango65 profile image
tango65 in reply to timotur

It is cabazitaxel and ADT in mCRPC:

thelancet.com/journals/lanc...

GP24 profile image
GP24 in reply to timotur

There is no head to head comparison between Lu177 and the triplet therapy in PEACE1. The side effects will be lower with Lu177.

Also, the PEACE1 trial is not designed to compare the triplet therapy with the combination of Abiraterone and ADT. Therefore you cannot be sure that the triplet therapy works better than just Abiraterone and ADT.

SeattleDan profile image
SeattleDan in reply to GP24

Thanks for pointing this trial out to me! A possibility... though it would seem I might end up just getting ADT alone.

GP24 profile image
GP24 in reply to SeattleDan

I zapped my lymph node mets with SBRT twice plus twice with Lu177.

tango65 profile image
tango65 in reply to SeattleDan

It is a risk of the randomized control trials with a SOC arm. I would not get ADT alone since ADT plus new anti androgens or chemo offer a better overall survival.

GP24 profile image
GP24 in reply to tango65

Tango, if you get into the control arm, in this trial you can cross-over and get the Lu177 therapy when there is progression detected.

SeattleDan profile image
SeattleDan in reply to GP24

Looks like I wouldn’t be eligible- my mets are still smaller than what’s required

Seasid profile image
Seasid in reply to SeattleDan

Yes! Good idea. Get Firmagon injections. I am very happy with firmagon, crestor 40 mg per day, metformin 3× 500 mg per day and doxycycline 100 mg per day. You can add abiraterone later. If you take early 6 cycles of docytaxel chemotherapy it woul be perfect.

MateoBeach profile image
MateoBeach

If I were in your situation, and I may be. (Will know at my next PSMA PET scan next month. Hormone sensitive and lymph node only disease so far.) I would go for Lu177 treatments abroad. This works better earlier rather than later. And it works better in lymph nodes than in bone or visceral mets. The Imminent approval expected in the USA will only be for castrate resistant. I see no advantage in waiting. You can get a video/ virtual consult and send a disc CD of your scan to get an experienced opinion from a doctor experienced with radioligand treatments, Lu177 and Ac225. GenesisCare in Australia is the one I consulted with. There are contacts for others in India and Germany in previous threads on this site. Good luck. It is a difficult decision and the spot SBRT or Cyberknife would very likely be futile since you are not oligometastatic.

slpdvmmd profile image
slpdvmmd

I concur with other comments suggesting go overseas for Lutetium +/- Actinium radioligand therapy. The United States is behind the power curve on radioligand therapy and will not catch up with current FDA approach to approval and study designs. You can contact international office at Heidelberg University and they will give you a link to upload your PSMA PET/CT and tell you if they think you are a candidate for radioligand therapy. I am sure there are similar systems in place at other overseas locations. As for "whack a mole" if any one had a real answer on it not being of benefit then studies such as the one I am familiar with at UCSF for cyberknife vs apalutamide (similar studies are available for proton beam) for lymph node mets would not still have on-going funding. "Whack a mole" IMO needs leave our vocabulary.

slpdvmmd profile image
slpdvmmd

Here is some published support for exploring radioligand therapy with lymph node metastasis and why I am so negative on the "Whack a mole" philosophy. Keep in mind you only see what are the limits of imaging so systemic targeted therapy seems logical at this point in time.Abstract of one paper

Real-World Data Analysis of Efficacy and Survival After Lutetium-177 Labelled PSMA Ligand Therapy in Metastatic Castration-Resistant Prostate Cancer

Danielle Meyrick, Marat Gallyamov, Shanthi Sabarimurugan, Nadia Falzone & Nat Lenzo

Targeted Oncology volume 16, pages369–380 (2021)Cite this article

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6 Citations

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Abstract

Background

Lutetium-177 prostate-specific membrane antigen (177Lu-PSMA) radioligand therapy is emerging as a promising treatment for metastatic castration-resistant prostate cancer refractory to established therapies. While there is an increasing body of survival and other data from retrospective analyses and prospective trials, there is no clear understanding of how best to predict therapy response and survival outcomes.

Objective

In this retrospective cohort analysis, we aimed to identify features that are associated with response to radioligand therapy and greater survival based on analysis of real-world data.

Patients and Methods

191 patients aged 70 ± 8 years with metastatic castration-resistant prostate cancer treated with radioligand therapy from November 2015 to February 2019 were included for analysis. Eligible patients had PSMA-expressing metastatic castration-resistant prostate cancer (confirmed by a 68Ga-PSMA-ligand positron emission tomography (PET)/computed tomography (CT) scan), an Eastern Cooperative Oncology Group performance status score ≤ 2 and no significant kidney, liver or bone marrow dysfunction (as characterised by kidney and liver function tests and a full blood count). Patients received one to five cycles of intravenous 177Lu-PSMA-ligand therapy. Endpoints included biochemical [prostate-specific antigen (PSA)] and radiologic (PSMA PET/CT) response, progression-free survival and overall survival, defined according to the Prostate Cancer Working Group 3 guidelines. Survival analysis was conducted by Kaplan–Meier estimation.

Results

Most individuals (89.5%) previously underwent first- and second-line systematic therapy. Of the 191 men treated with 452 cycles with mean injected activity of 6.1 ± 1.0 GBq per cycle, 159 patients were assessed for a biochemical response defined as a PSA decline ≥ 50% from baseline. A ≥ 50% PSA decline was observed in 89 (56%) patients, while any PSA decline occurred in 120 (75%) men. For the entire cohort, median values (interquartile range) of overall survival [n = 191], PSA progression-free survival [n = 132] and PET/CT progression-free survival were 12 (5–18), 4 (3–8) and 6 (3–10) months, respectively. Survival analysis confirmed better outcomes in individuals who had demonstrated therapy response. Predominantly lymph node metastatic disease and chemotherapy-naïve status were significant pre-therapy factors associated with longer survival. Baseline PSA was significantly linked to survival outcomes: lower levels predicted a lower risk of death and disease progression. Treatment-related adverse events included grade 3 or 4 haematological (12%), grade 1 or 2 renal (4.5%), and grade 3 or 4 clinical events (5.7%).

Conclusions

Our findings suggest that 177Lu-PSMA radioligand therapy provides a significant response rate with a low toxicity profile. The evidence promotes greater efficacy of radioligand therapy in predominantly lymph node metastatic castration-resistant prostate cancer, and in individuals with chemotherapy-naïve status and lower levels of baseline PSA.

two more complete manuscript links

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

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

SeattleDan profile image
SeattleDan in reply to slpdvmmd

Thank you so much for complete report!

bean1008 profile image
bean1008

I’m curious Dan…are you being treated at SCCA? Who’s your MO? Best of luck to you!

SeattleDan profile image
SeattleDan in reply to bean1008

yep. thanks!

SeattleDan profile image
SeattleDan

So many of you make such a good case for getting Lutetium 177 abroad. The one big problem being that unless we sell our house, the cost seems prohibitive. Does MaleCare allow us a GoFundMe-type option?

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