PSMA and treatment of micromets

[napoleondynamite]

My urologists have started sending like everyone with a rising PSA for PSMA testing.

Today I got a referral for these teeny tiny retroperitoneal nodes. Technically, would be amenable to a small IMRT field.

I got another referral today for two super small but avid lung nodules.

I have no idea what to do with this. Would you guys be SBRTing the lung nodules and treating the LN's?!

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[evilbooyaa]

Oligometastatic disease in prostate cancer treatment, now more detectable with new imaging modalities.

Makes sense for CRC and NSCLC, seems like it would make sense for something with generally slower growth potential. Can't say there's evidence for it though. Can't hurt to do a few (insurance willing) and see how they do.

 

[nkmiami]

where can you get psma?

 

[napoleondynamite]

The ones I'm seeing are from UCLA. Cash price for the test is $4,500. I saw an interesting/entertaining talk at ASCO - guy from Australia said they do it for much less - logged into Expedia and showed that with flight, 4-star hotel and the test, it's about the same price to get it in Australia

 

[nkmiami]

does anyone know how psma stacks up against axumin?

 

[seper]

how big the lesions need to be, for these new tests to be reliable?

 

[napoleondynamite]

how big the lesions need to be, for these new tests to be reliable?

I wish I knew the answer to this..does anyone?

I mean the supposed mets on these scans are <1mm, but very hot.

I just don't know what to do with these.

I'm so confused, because urologists are sending me patients! lol

I hate to cut off my new referrals by not treating. But I just don't know how reliable these scans really are yet. How often do we see lung mets for prostate cancer?

 

[medgator]

I wish I knew the answer to this..does anyone?

I mean the supposed mets on these scans are <1mm, but very hot.

I just don't know what to do with these.

I'm so confused, because urologists are sending me patients! lol

I hate to cut off my new referrals by not treating. But I just don't know how reliable these scans really are yet. How often do we see lung mets for prostate cancer?

Sounds like a good networking opportunity for a journal club, sponsored by the psma rep

 

[napoleondynamite]

haha yup Medgator

 

[Palex80]

I have had some limited experience with PSMA-PET. It is being reimbursed since the beginning of this year in Switzerland and the debate when and which patients to send to PSMA is already there.

In the past we had some urologists that would actually send the patient for consultation on adjuvant RT after a pT3a/b R1-resection, especially the ones where the R1-region was several mm and not a tiny little spot on the specimen.
With the introduction of PSMA-PET this practice had changed with the urologist advocating to closely monitor the PSA and send the patient to PSMA before salvage RT in the case of rising PSA.

The next problem that arises is WHEN to do the PSMA-PET. I have seen patients getting PSMA-PETs at very low values of PSA. The reimbursement rules are rather vague formulated ("biochemical recurrence"), thus some urologists tend to stick to the 0.2 ng/ml threshold before sending the patient to get his PSMA-PET, while others state that 3 rising values of PSA are enough.
Nowadays with the ultrasensitive PSA-testing available, you can easily get 3 consecutive rises within a few months. And we all know that there are always some prostate patients, that will like to get their PSA tested monthly after RPE.
So I am seeing patients now like these (PSA: 12 ng/ml -> RPE -> pT3a R1 -> PSA-6-weeks-postop: 0.004 ng/ml -> PSA-10-weeks-postop: 0.006 ng/ml -> PSA-14-weeks-postop: 0.007 ng/ml -> PSA-18-weeks postop: 0.008 ng/ml -> urologist declares "PSA-recurrence" -> PSMA-PET-CT: negative). Now what?

Consultations with the patients are then rather stressfull since you need to explain to the patient that the PSMA-PET-CT was done way too early and a negative result means nothing.
It's certainly hard for a patient, to consent to an adjuvant treatment, when the multi-thousand-$/€-examination he had was negative...

And then there are always these "surprise-surprise" moments when ordering a PSMA-PET.

First case: Rising PSA post RPE at 0.4ng/ml. PSMA-uptake in the prostatic fossa, no pelvic nodes. However tiny lymph nodes of 3-4mm in max. diameter being valued as "PSMA-positive" by the radiologists in the retroperitoneal area.
So, what do you do?
a) Call it metastatic M1(LYM) and send the patient to upfront ADR +/- docetaxel, forget about salvage RT?
b) Irradiate the prostatic fossa and ignore the nodes?
c) Irradiate the prostatic fossa and give him hormones?
d) Irradiate everything that's positive on PSMA-PET?

We went for a). I hope it was a good call.

Second case: PSMA-PET performed after PSA-rise following salvage RT to the prostatic fossa. PSA had dropped below 0.03 ng/ml after salvage RT and sadly rose again to 0.8 ng/ml before PSMA-PET. I was hoping to find a solitary lymph node in the pelvis and push for RT and/or resection as a last hope of curative treatment. PSMA-PET picked up solitary bone lesion in the pelvis hardly visible in CT + mediastinal nodes + a pulmonary lesion (<2cm), all lesions more or less with the same uptake in PSMA. Biopsy in the mediastinum showed NSCLC! Bone lesion was biopsied too and was NSCLC as well... The patient went to first line immunotherapy.

 

[DoctwoB]

I have had some limited experience with PSMA-PET. It is being reimbursed since the beginning of this year in Switzerland and the debate when and which patients to send to PSMA is already there.

In the past we had some urologists that would actually send the patient for consultation on adjuvant RT after a pT3a/b R1-resection, especially the ones where the R1-region was several mm and not a tiny little spot on the specimen.
With the introduction of PSMA-PET this practice had changed with the urologist advocating to closely monitor the PSA and send the patient to PSMA before salvage RT in the case of rising PSA.

The next problem that arises is WHEN to do the PSMA-PET. I have seen patients getting PSMA-PETs at very low values of PSA. The reimbursement rules are rather vague formulated ("biochemical recurrence"), thus some urologists tend to stick to the 0.2 ng/ml threshold before sending the patient to get his PSMA-PET, while others state that 3 rising values of PSA are enough.
Nowadays with the ultrasensitive PSA-testing available, you can easily get 3 consecutive rises within a few months. And we all know that there are always some prostate patients, that will like to get their PSA tested monthly after RPE.
So I am seeing patients now like these (PSA: 12 ng/ml -> RPE -> pT3a R1 -> PSA-6-weeks-postop: 0.004 ng/ml -> PSA-10-weeks-postop: 0.006 ng/ml -> PSA-14-weeks-postop: 0.007 ng/ml -> PSA-18-weeks postop: 0.008 ng/ml -> urologist declares "PSA-recurrence" -> PSMA-PET-CT: negative). Now what?

Consultations with the patients are then rather stressfull since you need to explain to the patient that the PSMA-PET-CT was done way too early and a negative result means nothing.
It's certainly hard for a patient, to consent to an adjuvant treatment, when the multi-thousand-$/€-examination he had was negative...

And then there are always these "surprise-surprise" moments when ordering a PSMA-PET.

First case: Rising PSA post RPE at 0.4ng/ml. PSMA-uptake in the prostatic fossa, no pelvic nodes. However tiny lymph nodes of 3-4mm in max. diameter being valued as "PSMA-positive" by the radiologists in the retroperitoneal area.
So, what do you do?
a) Call it metastatic M1(LYM) and send the patient to upfront ADR +/- docetaxel, forget about salvage RT?
b) Irradiate the prostatic fossa and ignore the nodes?
c) Irradiate the prostatic fossa and give him hormones?
d) Irradiate everything that's positive on PSMA-PET?

We went for a). I hope it was a good call.

Second case: PSMA-PET performed after PSA-rise following salvage RT to the prostatic fossa. PSA had dropped below 0.03 ng/ml after salvage RT and sadly rose again to 0.8 ng/ml before PSMA-PET. I was hoping to find a solitary lymph node in the pelvis and push for RT and/or resection as a last hope of curative treatment. PSMA-PET picked up solitary bone lesion in the pelvis hardly visible in CT + mediastinal nodes + a pulmonary lesion (<2cm), all lesions more or less with the same uptake in PSMA. Biopsy in the mediastinum showed NSCLC! Bone lesion was biopsied too and was NSCLC as well... The patient went to first line immunotherapy.

Urologist here, found this to be a very interesting topic. We aren't using PSMA yet in clinical practice at my institution given the lack of appreciable evidence of any change in course or outcome. Treatment of oligometastaic disease may have some benefit, but this needs to be studied before it should be considered outside of the trial setting. There is more and more emerging evidence for local control to the prostate, whether surgical or XRT for metastatic or Clinically mode positive disease.

As a brief aside you should strongly consider sending patients for up front ADT plus abiretarone and prednisone now over docetaxel based on Two recent Nejm rcts. True it was compared to ADT alone and not upfront docetaxel, but given the side effect profiles that is what I would want for myself or family.

 

[nkmiami]

A Pilot Study of a Multimodal Treatment Paradigm to Accelerate Drug Evaluations in Early-stage Metastatic Prostate Cancer. - PubMed - NCBI

some patients at MSKCC with metastatic disease were cured of their prostate cancer apparently with aggressive local therapies and SBRT/surgery to mets added to their systemic treatments, so I think better imaging has promising potential benefits

 

[Palex80]

As a brief aside you should strongly consider sending patients for up front ADT plus abiretarone and prednisone now over docetaxel based on Two recent Nejm rcts. True it was compared to ADT alone and not upfront docetaxel, but given the side effect profiles that is what I would want for myself or family.

I disagree and you stated yourself already why.
There is no clear evidence of a superiority of any given approach. It's clear you should combine ADT with "something", but noone knows what is the optimal "something".
And the whole field is going to get even more complicated when data on upfront enzalutamide + ADT vs. ADT will be published, which will also certainly be positive as well, since enazlutamide is even more potent that abiraterone (although never published as tested head to head yet). Are you going to switch to upfront enzalutamide then?

At the end of the day, the metastatic prostate patient that is going to live for the longest time is going to be the prostate patient who was given the "chance" to have as many lines of treatment as possible. The one that had "all the drugs". In my experience, lots of metastatic prostate patients "miss" the window of opportunity to get chemo, because urologists + oncologists gave several lines of other drugs (abiraterone, alpharadine, enzalutamide) for as long as possible, stressing out to the patient how important it is to "avoid" chemo. At some point the patients are simply too sick and too weak to get chemo. That's why I am an advocate of giving chemo upfront or at least at the moment when you think the patient will tolerate it the best. And that's usually at the beginning of metastatic disease. We now even have some evidence pointing out that chemo may be valuable even in locally advanced tumors together with ADT + RT.

 

[medgator]

I disagree and you stated yourself already why.
There is no clear evidence of a superiority of any given approach. It's clear you should combine ADT with "something", but noone knows what is the optimal "something".
And the whole field is going to get even more complicated when data on upfront enzalutamide + ADT vs. ADT will be published, which will also certainly be positive as well, since enazlutamide is even more potent that abiraterone (although never published as tested head to head yet). Are you going to switch to upfront enzalutamide then?

At the end of the day, the metastatic prostate patient that is going to live for the longest time is going to be the prostate patient who was given the "chance" to have as many lines of treatment as possible. The one that had "all the drugs". In my experience, lots of metastatic prostate patients "miss" the window of opportunity to get chemo, because urologists + oncologists gave several lines of other drugs (abiraterone, alpharadine, enzalutamide) for as long as possible, stressing out to the patient how important it is to "avoid" chemo. At some point the patients are simply too sick and too weak to get chemo. That's why I am an advocate of giving chemo upfront or at least at the moment when you think the patient will tolerate it the best. And that's usually at the beginning of metastatic disease. We now even have some evidence pointing out that chemo may be valuable even in locally advanced tumors together with ADT + RT.

Good points. Plus zytiga must be given with steroids while xtandi avoids that.

The chemo data with xrt and long term adt showing overall survival was compelling enough to be included in current guidelines.

 

[DoctwoB]

All fair points. Until we have comparison data between ADT + chemo vs. abiretarone vs. enzalutamide there will be a lot of individualized decision making based on patient specific factors. For a healthier patient in his 50s with bulky disease, getting up front chemotherapy may be the way to go. For an older, less healthy patient with lower disease burden, ADT + abiretarone or enzalutamide could likely provide better QoL with equivalent or near equivalent survival, and a high liklihood of death from other causes before requiring chemotherapy. While abi does require prednisone, it tends to have less fatigue then enza, though with more mineralocorticoid ADRs. Both are great drugs and will have their uses based on patient preference for side effect profile.

 

[seper]

I keep seeing this hypothesis, metastatic prostate Ca will be cured, like colorectal cancer with one liver met... That goes against classic thinking about biologic behavior of metastatic prostate Ca (diffuse). Are there any data yet?

A Pilot Study of a Multimodal Treatment Paradigm to Accelerate Drug Evaluations in Early-stage Metastatic Prostate Cancer. - PubMed - NCBI

some patients at MSKCC with metastatic disease were cured of their prostate cancer apparently with aggressive local therapies and SBRT/surgery to mets added to their systemic treatments, so I think better imaging has promising potential benefits

 

[Palex80]

I keep seeing this hypothesis, metastatic prostate Ca will be cured, like colorectal cancer with one liver met... That goes against classic thinking about biologic behavior of metastatic prostate Ca (diffuse). Are there any data yet?

Dear Seper, I fully agree with you. I do not think that prostate cancer will be cured and IMHO colorectal cancer with solitary liver mets is an exception. The whole point of CRC mets in the liver is the hematogenic spread of the disease into the liver by the draining vessels of the colon through the vena portae. This actually makes sense from the anatomic point of view, since the liver acts like a filter.
This is not the case in prostate cancer. There is no draining vessel of the prostate delivering venous blood exclusively to some vertebra in the spine, which then leads to metastasis there.

Actually I have to say that I am witnessing more and more aggressive local therapies in CRC nowadays which sometimes make me wonder what evidence these strategies are based upon. Surgeons and med. oncologists keep pointing out that CRC-patients with limited liver mets can be cured in 20% of cases, yet I am witnessing patients undergoing liver resection (up to hemihepatectomy) for 5+ liver mets, sometimes even combined local approaches for patients with liver and lung mets. Are my colleagues a bit too eager to extrapolate data on patients with limited liver mets to a broad spectrum of patients with multiple mets?
I generally try to keep quiet in the tumor board, not much to gain there for our discipline, yet it's scary sometimes. Occasionally I get to SBRT a liver or a lung met, they would'nt like to cut out or RFA upon.

 

[napoleondynamite]

Dear Seper, I fully agree with you. I do not think that prostate cancer will be cured and IMHO colorectal cancer with solitary liver mets is an exception. The whole point of CRC mets in the liver is the hematogenic spread of the disease into the liver by the draining vessels of the colon through the vena portae. This actually makes sense from the anatomic point of view, since the liver acts like a filter.
This is not the case in prostate cancer. There is no draining vessel of the prostate delivering venous blood exclusively to some vertebra in the spine, which then leads to metastasis there.

Actually I have to say that I am witnessing more and more aggressive local therapies in CRC nowadays which sometimes make me wonder what evidence these strategies are based upon. Surgeons and med. oncologists keep pointing out that CRC-patients with limited liver mets can be cured in 20% of cases, yet I am witnessing patients undergoing liver resection (up to hemihepatectomy) for 5+ liver mets, sometimes even combined local approaches for patients with liver and lung mets. Are my colleagues a bit too eager to extrapolate data on patients with limited liver mets to a broad spectrum of patients with multiple mets?
I generally try to keep quiet in the tumor board, not much to gain there for our discipline, yet it's scary sometimes. Occasionally I get to SBRT a liver or a lung met, they would'nt like to cut out or RFA upon.

I see your point. But does it not stand to reason that if you treated the prostate with RT, then catch early mets in the untreated LN's from a rising PSA - perhaps those patients can truly be salvaged? I agree these need to be evaluated on a case-by-case basis. I saw another patient's scan this week that was post-prostatectomy with rising PSA and the urologist sent for PSMA, clear local uptake, so they sent to me for salvage. I see a role if the test is as good as they are saying it is.

Not sure I'll be radiating lung mets that are <1mm. But not saying I won't either. If I have a young patient in front of me and they get this news from their scan that they have one likely lung met - the downside of a teeny tiny SBRT field there is usually pretty nil and at minimim psychological impact for the patient huge. I'd probably give them the benefit of the doubt if it was one met and then kick the can for a bit.

But I also have seen a patient that is 2 years out from EBRT and PSMA picked up several retroperitoneal nodes with 1mm mets - urologist is planning RPLND..which I think is nuts. Am I a hypocrite?

 

[evilbooyaa]

I see your point. But does it not stand to reason that if you treated the prostate with RT, then catch early mets in the untreated LN's from a rising PSA - perhaps those patients can truly be salvaged? I agree these need to be evaluated on a case-by-case basis. I saw another patient's scan this week that was post-prostatectomy with rising PSA and the urologist sent for PSMA, clear local uptake, so they sent to me for salvage. I see a role if the test is as good as they are saying it is.

Not sure I'll be radiating lung mets that are <1mm. But not saying I won't either. If I have a young patient in front of me and they get this news from their scan that they have one likely lung met - the downside of a teeny tiny SBRT field there is usually pretty nil and at minimim psychological impact for the patient huge. I'd probably give them the benefit of the doubt if it was one met and then kick the can for a bit.

But I also have seen a patient that is 2 years out from EBRT and PSMA picked up several retroperitoneal nodes with 1mm mets - urologist is planning RPLND..which I think is nuts. Am I a hypocrite?

Not overtly because the morbidity of RPLND compared to morbidity of SBRT isn't comparable, but in lines of thought, yeah somewhat. If aggressive focal therapy is good for the goose, can't an argument be made that it's good for the gander?

 

[Palex80]

I see your point. But does it not stand to reason that if you treated the prostate with RT, then catch early mets in the untreated LN's from a rising PSA - perhaps those patients can truly be salvaged? I agree these need to be evaluated on a case-by-case basis. I saw another patient's scan this week that was post-prostatectomy with rising PSA and the urologist sent for PSMA, clear local uptake, so they sent to me for salvage. I see a role if the test is as good as they are saying it is.

Not sure I'll be radiating lung mets that are <1mm. But not saying I won't either. If I have a young patient in front of me and they get this news from their scan that they have one likely lung met - the downside of a teeny tiny SBRT field there is usually pretty nil and at minimim psychological impact for the patient huge. I'd probably give them the benefit of the doubt if it was one met and then kick the can for a bit.

But I also have seen a patient that is 2 years out from EBRT and PSMA picked up several retroperitoneal nodes with 1mm mets - urologist is planning RPLND..which I think is nuts. Am I a hypocrite?

I agree. There is clearly a difference between microscopic/macroscopic spread to regional lymph nodes and non-regional lymph node metastasis or non-draining, non-solitary organ metastases.
RPLND for prostate cancer is experimental, toxic and probaby will change nothing in terms of OS.