Should we delay 2nd cycle of Lu-177 if response to 1st cycle is very good ?

[dudubaya]

Hi All,

Father's 1st cycle Lu-177 PSMA response has been very good with PSA dropping from 31.7 to 1.16 and his blood counts have only dropped mildly , he is due for his 2nd cycle next weekend, while we are thankful to almighty for such a good response there are a couple of things that I am trying to figure out :-

1. Assuming there are much lesser cancer cells than last time the radiation will damage more healthy cells than cancer cells this time, should we delay the 2nd cycle by couple of weeks or do it when PSA rises again in order to have optimal balance between benefit and SE ?

2. As there is a cap on total number of cycles (6) that can be administered , will pausing after a couple of good response cycles be a good strategy to save the cycles for later use ? This article seems to indicate so

jnm.snmjournals.org/content...

However the Nuclear Medicine Doctor insists on going ahead with the 2nd cycle as planned and consider re-evaluation only after 2nd cycle, as per him delaying is only considered when patients have SE and need recovery time

After much pleading he has suggested to redo the PSMA PET Scan again and take the call based on SUV uptake probably with a reduced dose and is confident that PSA would have risen by then, but what if trend continues(it drops further) do we still go ahead with the planned cycle or space it out till PSA rises again?

Father is on regular ADT +Enza , any info or suggestion is much appreciated

Thanks

[Tall_Allen]

A good response on 1 treatment is a signal to keep going. Kidney problems is a reason to stop.

He can have a SPECT scan after each infusion.

[dudubaya in reply to Tall_Allen]

Thanks TA, he does have SPECT post therapy as protocol

[RyderLake2]

Hello,

I have completed four cycles of Lutetium. Why on earth would you want to stop? A good reaction is an indication you should continue with the treatment not stop it. You should only stop if the side effects are so horrendous from Lutetium that you cannot continue. Listen to your nuclear medicine doctor and consider yourself fortunate to get this treatment. Many PCa sufferers who cannot afford this drug or live in areas where Lutetium is unavailable would love to be in your shoes!

[dudubaya in reply to RyderLake2]

Thanks RyderLake2.

[tennis4life]

Continue on. Pausing is absolutely not recommended. Follow the doctor's advice on this one.

[dudubaya in reply to tennis4life]

Thanks tennis4life

[GP24]

Combining Enzalutamide and Lutetium 177 is a very effective therapy. thelancet.com/journals/lano... If you get a PSMA PET/CT you can see if there is enough cancer to target with Lutetium 177. In general you will get at least two cycles and then get a PSMA PET/CT. After that you can take a longer break, although this is not recommended in the Pluvicto "package insert". Enzalutamide may work well after debulking the tumor with Lutetium 177.

[dudubaya in reply to GP24]

Thanks GP24, that is what I wanted to know.

[Miccoman]

I agree that since it is working you should continue.

I had the full 6 cycles that ended about a year ago, and my MOs, who were urging me to go for a clinical trial, now think I should do an SOC treatment. I checked with my RO and she said I was good for another round of Pluvicto (we haven't met yet, so I am not sure if that is the complete 6 cycles or fewer).

Other options for me are Cabazitaxel (I didn't do well with docetaxel, though) or Abiraterone (but that just suppresses growth, not kill the tumors).

I guess what I'm saying is that the 6 cycles are not a lifetime limit. Check with your RO and nuclear med doctor to understand what applies in your situation.

[dudubaya in reply to Miccoman]

Thanks for the info Miccoman, will definitely check with the doc on whether future rounds are possible on need basis after 6 full cycles are exhausted

[GP24 in reply to dudubaya]

After six cycles further rounds are possible. But I am afraid the insurance will not pay for these.

[Seasid in reply to GP24]

It also depends (I believe) what the PSMA pet scan will show and I would if I could also have an FDG pet scan. I like the ides of debunking mainly because I think that the Enzalutamide works better if the tumour load is small. Even lutetium PSMA treatment works better if the tumour volume is under 200 ml if I recall correctly. Ask all these questions from your doctor.

[GP24 in reply to Seasid]

Because the patient just got one cycle yet I did not want to get into detail. I agree with you, except I do not think Lutetium works better at a lower tumor volume.

[Seasid in reply to GP24]

I believe the Hofman group concluded that the lutetium PSMA treatment works best when the volume is under 200 ml plus the SUV max (if I am correct) is above 10.

Maybe I will ask ChatGPT to confirm this because maybe my memory is not the best.

[Seasid in reply to Seasid]

Your recollection aligns with findings from the TheraP trial led by Professor Michael Hofman. In this study, a prostate-specific membrane antigen (PSMA) PET SUV_mean of 10 or higher was evaluated as a predictive biomarker for response to [^177Lu]Lu-PSMA-617 therapy. Additionally, a metabolic tumor volume (MTV) of 200 mL or higher on FDG-PET was assessed as a prognostic biomarker. The trial found that patients with an SUV_mean of 10 or higher had a higher prostate-specific antigen (PSA) response rate to [^177Lu]Lu-PSMA-617 compared to cabazitaxel. Conversely, patients with an MTV of 200 mL or higher had a lower PSA response rate, indicating that higher tumor volume is associated with poorer outcomes.

These findings suggest that [^177Lu]Lu-PSMA-617 therapy is more effective in patients with high PSMA expression (SUV_mean ≥ 10) and lower tumor burden (MTV < 200 mL).

ChatGPT said

[GP24 in reply to Seasid]

Hofman uses an FDG PET-CT to determine PSMA negative tumor. If there is a lot of PSMA negative tumor, he will not treat the patient with Lutetium. A separate study determined that the patients with a lot of PSMA negative tumor have a life expectancy of three months after being excluded from these trials.

[Seasid in reply to GP24]

Thanks for clarifying.

[Miccoman in reply to GP24]

Depends entirely on insurance, of course. I have traditional Medicare and I called them and they told me there are no limits on Pluvicto. If one has an Advantage plan, or other private insurance, the Benefits Manager will certainly do everything they can to avoid paying the huge cost for this treatment.

[Justfor_]

During the 90s some ROs launched the idea of Adaptive RT (ART). In a nutshell, RT planning is revised as the fractions proceed with changes guided by imaging findings.

youtube.com/watch?v=5XgpqCL...(Not working as expected?)

To be pragmatic, this has a hell of more planning involved compared to 20-40 iterations of a "master" plan, so didn't make it to the everyday clinical practice.

I am self-administering an adaptive Bicalutamide dosage, as I have full control of what I take and spare the BS silly/lazy docs like to recount.

[dudubaya in reply to Justfor_]

Thanks Justfor_ . I am unable to find much on the net for something like adaptive Lu-177

[Seasid]

I would stop the lutetium PSMA treatment and just continue with Enzalutamide. I am not a doctor therefore my instinct don't count. I would save some money.

I always thought that if the PSMA SUV max is under 10 than the radiation is either not effective or could actually damage the kidneys.

I would save it for later. And maybe continue with chemotherapy 3 cycles if the MO agree with that.

[Seasid in reply to Seasid]

I understand that the doctors don't like to stop. They don't want to lose money.

[Seasid in reply to Seasid]

It sounds like you're carefully weighing your options regarding treatment. While cost is a factor, the decision should ultimately be based on efficacy and safety, in consultation with your oncologist.

Your concern about PSMA SUV max being under 10 is valid—lower uptake could mean less effectiveness of Lutetium-177 PSMA therapy. Some studies suggest that higher SUV max values correlate with better responses. However, the threshold for effectiveness varies, and other factors like overall disease burden, previous treatments, and kidney function play a role.

Saving Lutetium-177 PSMA for later might be reasonable if other treatments are still effective. If your oncologist agrees, continuing with Enzalutamide and considering chemotherapy could be a solid approach. Have you discussed these concerns with your MO yet?

ChatGPT said

[dudubaya in reply to Seasid]

Thanks for understanding it Seasid, you have exactly echoed my concerns

[Christ3lover]

Please do not stop the 177 Lutetium. It kills cancer cells. Enzalutamide only represses Prostate cancer. Stopping the 177 Lutetium would allow the cancer to grow back. Hit it with the 177 Lutetium until it's dead. How many treatments that will take - ask someone smarter than I

[Seasid in reply to Christ3lover]

The downside of continuing with lutetium is that you may wipe out the PSMA avid cancer but the PSMA negative could repopulate the empty space. If you wipe out all the PSMA positive cancer you could end up with the PSMA negative CRPC metastatic prostate cancer and the survival rate is only 3 months. I personally for myself wouldn't have a guts to do that. It is a very serious condition.

[Seasid in reply to Christ3lover]

It’s a tough balance between aggressively treating the cancer and managing the risks of treatment resistance. Lutetium-177 PSMA therapy is effective at targeting PSMA-positive cancer cells, but if there’s a mix of PSMA-positive and PSMA-negative cells, eliminating only the PSMA-positive ones might leave room for the more resistant, PSMA-negative cancer to take over.

That’s why some oncologists might suggest combining treatments—using Lutetium-177 to shrink the disease while keeping other therapies like Enzalutamide or chemotherapy in play to suppress resistant cells. If the goal is long-term control rather than just immediate elimination, strategic sequencing of treatments could be crucial.

Have you discussed PSMA-negative disease risks with your oncologist? They might recommend periodic scans or biopsies to monitor for treatment-resistant clones.

ChatGPT said

[Seasid in reply to Seasid]

Just to let you know that you could never cure the oligomethastatic prostate cancer with lutetium because the PSMA negative CRPC metastatic prostate cancer will survive, repopulate the space and kill you. It could be even worse than Enzalutamide.

[Seasid in reply to Seasid]

You're absolutely right—Lutetium-177 PSMA therapy isn't a cure, especially in the context of oligometastatic or metastatic prostate cancer. It selectively targets PSMA-positive cells, but any PSMA-negative cells will persist and could become dominant over time. This is one of the major challenges in treating advanced prostate cancer: the risk of treatment resistance and tumor evolution.

That’s why many oncologists use a combination approach, integrating hormonal therapies like Enzalutamide, chemotherapy, and even newer agents that target different pathways. The key is finding a balance between aggressive treatment and managing the emergence of resistant disease.

Are you considering alternative strategies, such as combination therapy or clinical trials? It might be worth discussing with your oncologist whether additional imaging or biomarkers can help guide the next steps.

ChatGPT said

[Christ3lover in reply to Seasid]

Thank you for your response. I did not mean to suggest 177 Lutetium with ADT. I apologize. I agree that combination therapy is a good idea. In my brain I think of it like 2 mobsters; one (the ADT) holds the cancer down and the 2nd (177 Lutetium or chemo) beats it to death. I want both. I'm going to listen to my oncologist, of course.

You talk about the PSMA positive disease being eliminated and the PSMA negative disease growing. I agree with your concern. However, does the PSMA positive disease repress the PSMA negative disease? Because otherwise I see no reason not to eliminate the PSMA positive disease.

[Seasid in reply to Christ3lover]

We don't know.

[Seasid in reply to Christ3lover]

You should understand that if you wipe out the PSMA positive cancer than the PSMA negative CRPC metastatic prostate cancer will repopulate the space.

I understand that you see benefits of wiping out the PSMA positive cancer. The problem is that the PSMA negative CRPC metastatic prostate cancer could be much more aggressive. I think a study from Peter Mac Callum cancer Centre from 2018 did show that the life expectancy was only 3 months for a cancer which didn't qualify for lutetium PSMA treatment. Peter Mac Callum cancer Centre did the PSMA pet scan and also the FDG pet scan and if the PSMA pet scan was clear but the FDG pet scan not than obviously you didn't qualify for the PSMA treatment and your life expectancy was only 3 months.

I am not a doctor but I realised that in Finland they do 3 cycles of lutetium PSMA treatment and after that 3 cycles of docetaxel chemotherapy. It makes sense to me but I don't really know.

[Seasid in reply to Seasid]

ChatGPT said

You're raising a very important point about PSMA-negative castration-resistant prostate cancer (CRPC) and the risk of more aggressive disease emerging after PSMA-positive cancer is treated. The concern is that if you eliminate PSMA-positive cells with Lutetium-177 PSMA therapy, you may leave behind or create an environment where PSMA-negative, potentially more aggressive, cancer cells thrive.

The study from the Peter MacCallum Cancer Centre in 2018 did indeed highlight the poor prognosis for patients whose PSMA PET scans were negative but had FDG PET-positive disease, with a median survival of about three months. This aligns with the idea that PSMA-negative disease can be more aggressive and resistant to targeted treatments like Lutetium-177.

Your mention of Finland's approach—combining Lutetium-177 PSMA therapy with docetaxel chemotherapy—makes a lot of sense. This sequential strategy could help address both PSMA-positive and PSMA-negative cancer cells. Docetaxel is a broad-spectrum chemotherapy that could target remaining PSMA-negative disease, potentially reducing the risk of rapid progression after PSMA therapy.

While more research is needed to determine the best sequencing or combination approaches, this kind of strategy reflects the evolving understanding of how prostate cancer adapts under selective pressure from treatments. Have you seen any recent data on how well this combination approach works in Finland or elsewhere?

ChatGPT said

[God_Loves_Me]

in India they do 2 dosage every year

India

[Seasid in reply to God_Loves_Me]

It looks like you might be referring to FDG PET scan, not "BDG scan."

An FDG PET scan (fluorodeoxyglucose positron emission tomography) is a type of imaging used to detect metabolically active cancer cells. It works by using a radioactive glucose tracer (FDG), which is taken up more by rapidly growing cancer cells. This scan is particularly useful for detecting PSMA-negative prostate cancer, which might not show up on a PSMA PET scan.

In the context of prostate cancer, an FDG PET scan is often used alongside a PSMA PET scan to assess tumor biology. If a tumor is PSMA-negative but FDG-positive, it may indicate a more aggressive, treatment-resistant form of metastatic prostate cancer, which is why it’s important for treatment decisions.

Did you mean FDG PET, or were you thinking of another type of scan?

ChatGPT said