PSMA PET and PSA

[Ray D. Ayshun]

I figure most of my questions have been asked before, and this maybe was discussed on Mednet, but at what point do you all think molecular imaging is a waste of time for recurrent prostate with respect to PSA? And for that matter bone scan? I know the data regarding PSA levels and sensitivity, but I also know we order things just because it's the way it's done. Anybody have a cutoff where they don't do anything molecular (axumin/PSMA)/nuclear (bone scan) regardless of NCCN recs?

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[Palex80]

Well, we have access and reimbursement to/for PSMA-PET-CT so we generally order that for all PSA persistence/recurrences cases.
Our nuclear medicine people keep arguing that it can be done at low levels and I've seen quite a few urologists order it at PSA values in the range of 0.2-0.3 ng/ml (whoch very often come back negative, since sensitivity is low and generally <50% in that range).
I've even see people doing it at 0.1 ng/ml, which is equivalent to opening the window and throwing 2k of dollar bills on the street...
The worst thing is communicating the negative findings of this ultra-early PSMA-PET-CTs to the patients. I've often heard patients arguing "Why do you need to irradiate me, the scan came back negative! Maybe I do not have a recurrence at all!"

With PSMA-PET-CT available, we never do the rest of the exams NCCN outlines anymore. I recall ordering those tests years ago, but they are really abysmal in terms of practice changing findings. I have also never ordered a prostate bed biopsy. If the imaging is positive, it is a local recurrence. And actually, I do not see much of a consequence. We dose-escalate those macroscopic recurrences to 70-74 Gy. I do not need a positive biopsy to justify an extra 4-8 Gy of dose...

One important point is that when you introduce PSMA-PET-CT in your practice you need to be aware that nuclear medicine specialists also have a learning curve. I've seen several examples of PSMA-positive finding being identified as "nodes" by nuclear medicine specialists which were merely ganglions in the retroperitoneal space. And there are some odd findings in the bone every now and then. I generally order another test to confirm a PSMA-PET-CT-finding in the bone, unless there are findings in the CT part too (sclerotic lesions). I do not believe that all focal PSMA-uptakes in the bone without any findings in CT/MRI are bone marrow lesions and we have actually sent patients for targetted biopsies of such lesions, which often came back negative. We treated only the prostatic bed and they responded well. So there are definetely some false positives out there and you need to watch out for them, they may ruin the only curative treatment chance the patient has in a worse case scenario.

 

[Chartreuse Wombat]

PSMA is only available at a limited number of centers. Axumin is more available.

PSA <0.5 after RP nothing unless PSMA is possible

PSA >0.5 after RP consider Axumin but many insurers will not approve (some require CT A/P and bone scan before approving which is silly)

Very much a moving target over the next 2 years as many versions of PSMA will become available in US

 

[Ray D. Ayshun]

PSMA is only available at a limited number of centers. Axumin is more available.

PSA <0.5 after RP nothing unless PSMA is possible

PSA >0.5 after RP consider Axumin but many insurers will not approve (some require CT A/P and bone scan before approving which is silly)

Very much a moving target over the next 2 years as many versions of PSMA will become available in US

What about a bone scan? It's even less sensitive, but cheaper, and I've had many issues with clear false positives making my life harder. Nonetheless, it's NCCN recommended, and there's always a lawyer in the back of your head saying just do it, better safe than sorry.

 

[medgator]

I figure most of my questions have been asked before, and this maybe was discussed on Mednet, but at what point do you all think molecular imaging is a waste of time for recurrent prostate with respect to PSA? And for that matter bone scan? I know the data regarding PSA levels and sensitivity, but I also know we order things just because it's the way it's done. Anybody have a cutoff where they don't do anything molecular (axumin/PSMA)/nuclear (bone scan) regardless of NCCN recs?

View attachment 325354

You missed the second part of the graphic that talks about "imaging not performed" before proceeding on to adt/xrt.

I'm with wombat on this one, just started firmagon on a high risk post op guy with PSA rise to 0.2 (gu decided to watch him at 0.1 despite t3a with 2 nodes involved). No imaging

 

[Ray D. Ayshun]

You missed the second part of the graphic that talks about "imaging not performed" before proceeding on to adt/xrt.

I'm with wombat on this one, just started firmagon on a high risk post op guy with PSA rise to 0.2 (gu decided to watch him at 0.1 despite t3a with 2 nodes involved). No imaging

I don't disagree. In fact, as wombat said, <.5 i do nothing. Otoh, I see lots of reactionary restaging. I'm not looking at nccn now, but If I remember, they casually talk about sensitivity as opposed to saying bone scan is not recommended if psa is under 1.

 

[Palex80]

One thing I find striking is that we "call" tests based on absolute PSA-values, while we know that tumors can have a quite diverse PSA-density.
If I see a PSA of 0.5 ng/ml in a patient who had a small pT3a with a preoperative PSA-value of 19 ng/ml, I am not confident that I will be able to spot something in comparison to a patient who had a pT3b yet a pre-operative PSA of merely 8 ng/ml.
Absolute PSA-values may be easy to memorize, but there's more behind that.


On a side note: Effective 01.01.2021 we will also have access and reimbursement to/for PSMA-PET-CT for primary staging of intermediate and high-risk prostate cancer. It will be interesting to see how many of those high-risk tumors we treat with surgery or RT will actually turn out to be metastatic with PSMA-imaging before local treatment...

EDITED first paragraph, I had forgotren a "not"

 

[DoctwoB]

One thing I find striking is that we "call" tests based on absolute PSA-values, while we know that tumors can have a quite diverse PSA-density.
If I see a PSA of 0.5 ng/ml in a patient who had a small pT3a with a preoperative PSA-value of 19 ng/ml, I am confident that I will be able to spot something in comparison to a patient who had a pT3b yet a pre-operative PSA of merely 8 ng/ml.
Absolute PSA-values may be easy to memorize, but there's more behind that.


On a side note: Effective 01.01.2021 we will also have access and reimbursement to/for PSMA-PET-CT for primary staging of intermediate and high-risk prostate cancer. It will be interesting to see how many of those high-risk tumors we treat with surgery or RT will actually turn out to be metastatic with PSMA-imaging before local treatment...

That's going to be the key question (part 2). I bet a large chunk of them, and the majority in the high risk by PSA (>20). The question will we treat those now clinically metastatic patients differently then we treated the same patient who was M0 before. I would argue that we should still be treating those patients with local therapy, but would definitely discuss the lack of data with patients and consider ablating mets if able. And while radiation for metastatic disease does have data, to what extent is that applicable in micrometastatic disease? Likely more so then low volume macrometastatic, but we need the data. There is plenty of data that patients who have undergone local therapy behave better once metastatic for prostate cancer, but that could very easily be driven by tumor biology differences between those who present localized vs. metastatic.

There are actually 9 RCTs accruing for RP in setting of low volume mets, not sure if any include PSMA in their protocols

The cytoreductive prostatectomy in metastatic prostate cancer: what the individual trials are hoping to answer - PubMed

While there are differences in each protocol, each trial aims to address different aspects of CRP in de novo HSPC. Therefore, the specific goals of each study and the limitations have to be taken into consideration when interpreting the results of these trials.

pubmed.ncbi.nlm.nih.gov

 

[Palex80]

That's going to be the key question (part 2). I bet a large chunk of them, and the majority in the high risk by PSA (>20). The question will we treat those now clinically metastatic patients differently then we treated the same patient who was M0 before. I would argue that we should still be treating those patients with local therapy, but would definitely discuss the lack of data with patients and consider ablating mets if able. And while radiation for metastatic disease does have data, to what extent is that applicable in micrometastatic disease? Likely more so then low volume macrometastatic, but we need the data. There is plenty of data that patients who have undergone local therapy behave better once metastatic for prostate cancer, but that could very easily be driven by tumor biology differences between those who present localized vs. metastatic.

There are actually 9 RCTs accruing for RP in setting of low volume mets, not sure if any include PSMA in their protocols

The cytoreductive prostatectomy in metastatic prostate cancer: what the individual trials are hoping to answer - PubMed

While there are differences in each protocol, each trial aims to address different aspects of CRP in de novo HSPC. Therefore, the specific goals of each study and the limitations have to be taken into consideration when interpreting the results of these trials.

pubmed.ncbi.nlm.nih.gov

I guess the med. oncs are going to cry out "He's metastatic" and call for early chemo or new anti-adrogen therapy and no local therapy. Some of them may call for ablation of mets, but it is likely that PSMA may produce more than just "oligometastatic" patients and rather "low burden metastatic" patients, for instance a dozen lymph nodes and perhaps 1-2 bone lesions.
We always have STAMPEDE Arm H to argue on radiotherapy to the primary in those patients, so 55/2.75 seem like a good choice here.
Ablation of mets in the oligometastatic setting has only shown better time to progression but has not influenced any other clinical meaningful endpoints so far in randomized trials (STOMP, ORIOLE).

 

[Palex80]

What about a bone scan? It's even less sensitive, but cheaper, and I've had many issues with clear false positives making my life harder. Nonetheless, it's NCCN recommended, and there's always a lawyer in the back of your head saying just do it, better safe than sorry.

We know that a bone scan is pretty bad in detecting bone lesions in newly diagnozed patients. This is not the same situation as in patients with a recurrence, but here's some food for thought.

Changing the referral criteria for bone scan in newly diagnosed prostate cancer patients

The aim of this study was to correlate the prostate-specific antigen (PSA) level and Gleason score with staging bone scan result in patients with a new diagnosis of prostate cancer in order to establish the feasibility of implementing the European Association ...

www.ncbi.nlm.nih.gov

It seems that bone scan is a waste of resources in GS <8 & PSA < 20 ng/ml.

 

[DoctwoB]

I guess the med. oncs are going to cry out "He's metastatic" and call for early chemo or new anti-adrogen therapy and no local therapy. Some of them may call for ablation of mets, but it is likely that PSMA may produce more than just "oligometastatic" patients and rather "low burden metastatic" patients, for instance a dozen lymph nodes and perhaps 1-2 bone lesions.
We always have STAMPEDE Arm H to argue on radiotherapy to the primary in those patients, so 55/2.75 seem like a good choice here.
Ablation of mets in the oligometastatic setting has only shown better time to progression but has not influenced any other clinical meaningful endpoints so far in randomized trials (STOMP, ORIOLE).

One of the onc attendants where I trained would say “you don’t want to die of bladder cancer with your bladder still in”. A bit self serving? Perhaps, but there was truth there. The patients dying with locally advanced and metastatic bladder CA were some of the saddest, most miserable cases I’ve seen. Bladders full of clot, bilateral nephrostomies, impossible to palliate.

likewise for prostate cancer up to 70% of patients with metastatic PC without therapy to the primary will need palliative surgery/procedures related the primary (TURP, nephrostomy most common). If it were me I’d want some form of local therapy.

 

[FreakFlag]

I figure most of my questions have been asked before, and this maybe was discussed on Mednet, but at what point do you all think molecular imaging is a waste of time for recurrent prostate with respect to PSA? And for that matter bone scan? I know the data regarding PSA levels and sensitivity, but I also know we order things just because it's the way it's done. Anybody have a cutoff where they don't do anything molecular (axumin/PSMA)/nuclear (bone scan) regardless of NCCN recs?

Axumin is legit and available in the US. However, PSMA per California & UMich data appears to outperform Axumin. PSMA is not widely available in the US currently since FDA approval was just weeks ago.

You can't be faulted for citing the 2020 ASCO guidelines during your next friendly neighborhood peer-to-peer phone call:

https://ascopubs.org/doi/full/10.1200/JCO.19.02757

"Rising PSA After Prostatectomy and Negative Conventional Imaging (either initial PSA undetectable with subsequent rise or PSA never nadirs to undetectable)

• Recommendation 4.4. For men for whom salvage radiotherapy is contemplated, NGI should be offered (PSMA imaging [where available]; 11C-choline or 18F-fluciclovine PET/CT; or PET/MRI, whole-body MRI, and/or 18F-NaF PET/CT) as they have superior disease detection performance characteristics and may alter patient management (Type: evidence based, benefits outweigh harms; Evidence quality: high; Strength of recommendation: strong)."

 

[evilbooyaa]

One of the onc attendants where I trained would say “you don’t want to die of bladder cancer with your bladder still in”. A bit self serving? Perhaps, but there was truth there. The patients dying with locally advanced and metastatic bladder CA were some of the saddest, most miserable cases I’ve seen. Bladders full of clot, bilateral nephrostomies, impossible to palliate.

likewise for prostate cancer up to 70% of patients with metastatic PC without therapy to the primary will need palliative surgery/procedures related the primary (TURP, nephrostomy most common). If it were me I’d want some form of local therapy.

I would palliate both of those situations with radiation rather than surgical resection as a first attempt.

55/20 is a mostly palliative dose of radiation for prostate cancer and although some are escalating higher off-trial to defintiive doses, I'd like to see data on the need for it before putting patients at extra risk of toxicity from what is still, a palliative treatment.

 

[DoctwoB]

There’s a big range of “palliative” in prostate cancer. Is it palliative if you’ve got a reasonable shot at living 10 years?

 

[Chartreuse Wombat]

I would palliate both of those situations with radiation rather than surgical resection as a first attempt.

55/20 is a mostly palliative dose of radiation for prostate cancer and although some are escalating higher off-trial to defintiive doses, I'd like to see data on the need for it before putting patients at extra risk of toxicity from what is still, a palliative treatment.

STAMPEDE argues 55 Gray in 20 fractions extends survival in oligometastatic patients.

 

[Palex80]

STAMPEDE argues 55 Gray in 20 fractions extends survival in oligometastatic patients.

But it still palliative, right?

 

[Chartreuse Wombat]

But it still palliative, right?

Depends on what you mean by palliative. My definition of palliative is to ameliorate symptoms. Most patients with oligometastatic prostate cancer have no symptoms to palliate. Radiation in this setting is not curative but palliative and curative are not complete antonyms

 

[evilbooyaa]

STAMPEDE argues 55 Gray in 20 fractions extends survival in oligometastatic patients.

As someone trained in an era where every treatment had to be defined as either 'curative' or 'palliative' for the purposes of CT simulation form, here are my thoughts:

Palliative chemotherapy improves survival as well in metastatic patients. Palliative does not mean that it cannot improve survival. It simply means that a treatment is not with curative intent.

SBRT in oligoprogressive disease is also palliative. Just because a treatment is palliative does not mean it has to be low dose. SRS for brain mets the vast majority of the time, also palliative.

Treatment is for either curative or palliative intent. IMO, if it's not curative intent, then it's palliative. Yes, it's not with the text book definition of 'improving symptoms' but until we have a 3rd option for billing/Evicore purposes, I'm not sure what the best system is.

There’s a big range of “palliative” in prostate cancer. Is it palliative if you’ve got a reasonable shot at living 10 years?

Let me put it this way - the local control with 55/20 is likely sufficient for the vast majority of patients with metastatic disease that local disease is not the reason that they pass away, which should be the goal of these situations.

I do not see any other specialty routinely recommending "palliative" or "non-curative" surgery in patients with diffuse metastatic disease more so than Urologists. Nephrectomy in mRCC, despite CARMENA results (systemic therapy not the same!!111), now prostatectomy in M1 pCa, without clinical trials to defend it (the way RT has STAMPEDE)? And are we seriously talking about cystectomy in metastatic bladder cancer rather than radiation for palliation as first-line?

Care to pontificate on why that is?

 

[DoctwoB]

STAMPEDE argues 55 Gray in 20 fractions extends survival in oligometastatic patients.

As someone trained in an era where every treatment had to be defined as either 'curative' or 'palliative' for the purposes of CT simulation form, here are my thoughts:

Palliative chemotherapy improves survival as well in metastatic patients. Palliative does not mean that it cannot improve survival. It simply means that a treatment is not with curative intent.

SBRT in oligoprogressive disease is also palliative. Just because a treatment is palliative does not mean it has to be low dose. SRS for brain mets the vast majority of the time, also palliative.

Treatment is for either curative or palliative intent. IMO, if it's not curative intent, then it's palliative. Yes, it's not with the text book definition of 'improving symptoms' but until we have a 3rd option for billing/Evicore purposes, I'm not sure what the best system is.



Let me put it this way - the local control with 55/20 is likely sufficient for the vast majority of patients with metastatic disease that local disease is not the reason that they pass away, which should be the goal of these situations.

I do not see any other specialty routinely recommending "palliative" or "non-curative" surgery in patients with diffuse metastatic disease more so than Urologists. Nephrectomy in mRCC, despite CARMENA results (systemic therapy not the same!!111), now prostatectomy in M1 pCa, without clinical trials to defend it (the way RT has STAMPEDE)? And are we seriously talking about cystectomy in metastatic bladder cancer rather than radiation for palliation as first-line?

Care to pontificate on why that is?

Many reasons.
Nephrectomy had level one data until CARMENA. Meaning (to a rough approximation) cytoreduction helped in the IFN IL2 era. It appears not to in the TKI era. Does it in the PDL1 era? Who knows? Oncologists I respect offer it selectively, either in the good risk group with vast majority of disease in kidney, very symptomatic masses or other select reasons.

M1 in CSPC is the same idea as radiation. Does local control improve survival? And you can’t fault urologists for not trying here, there are 9 RCTs that have or are accruing to answer this question. In the meanwhile, some offer it selectively for palliative reasons or to prevent future local failure. Of note, STAMPEDE showed no difference in rates of local symptomatic failure between xrt and no xrt groups. I expect surgery to do better in this regard. Note in Prostate cancer local failure usually isn’t a cause of death, but it is often a cause of misery. Finally for radonc being high and might about data it seemed awfully fast to adopt xrt as SOC in M1 PC based on a secondary subgroup analysis 🤔? (For the record, I don’t think it’s wrong but the insufficient data argument goes both ways).

And yes, palliative cystectomy is a thing and necessary in some cases. I’ve never seen XRT palliate an end stage bladder successfully.

 

[w00tz]

I think prostate radiation for patients with limited M1 disease should be in the same category as giving 60Gy in chemo for GBM.

 

[ramsesthenice]

My two cents to the original question: AXUMIN and Gallium PSMA PETs are not as helpful as you might think in current practice. I have used a ton of both (we were a US trial site). PSMA Gallium PETs are clearly a cut above AXUMIN but really they are more helpful at ruling disease out than pinpointing occult metastatic disease. Can help you feel better about excluding juicy negative nodes and sometimes they are helpful pushing you to boost small nodes that are clearly positive. They are as often confusing as they are helpful for bone lesions as referenced above (lots of false positives). More often than not though, they really just tell you what you would guess on a CT.

Where could they be helpful?

PET Directed vs comprehensive nodal salvage therapy (still controversial at best)

Better nodal staging in the pre-op setting which should be covered soon.

For most salvage cases though, they can help the patient feel better that “you found my cancer” which you probably would have found anyway. Don’t get me wrong, they can be very useful and I do get them. But if you are expecting to be blown away or see dramatic shifts in practice prepare to be disappointed.

 

[Chartreuse Wombat]

"they are more helpful at ruling disease out " Not sure the data supports that statement

SPIN-High specificity helps to rule in
SNOUT-High sensitivity helps to rule out

The data that I have seen suggests that the specificity of PSMA is High (90+%) and the sensitivity is Low (60-80%)...the opposite of your statement.

Happy to be corrected

 

[medgator]

I think prostate radiation for patients with limited M1 disease should be in the same category as giving 60Gy in chemo for GBM.

???

 

[Ray D. Ayshun]

???

As in, a treatment that will help a patient live longer.

 

[Palex80]

PET Directed vs comprehensive nodal salvage therapy (still controversial at best)

There is hope!

ClinicalTrials.gov

clinicaltrials.gov

 

[Palex80]

As in, a treatment that will help a patient live longer.

It's palliative, you just don't say it out loud...

 

[medgator]

It's palliative, you just don't say it out loud...

Seeing a lot of 1+ yr folks on Optune these days

 

[Ray D. Ayshun]

It's palliative, you just don't say it out loud...

On a long enough timeline, its all palliative.

 

[ramsesthenice]

On a long enough timeline, its all palliative.

Literally any radiation for low volume prostate cancer is less palliative than “definitive” RT for unresectable GBM or pancreatic cancer.

 

[Ray D. Ayshun]

Literally any radiation for low volume prostate cancer is less palliative than “definitive” RT for unresectable GBM or pancreatic cancer.

If it's about survival, then irradiating someone else's prostate is more definitive than treating a gbm, or for that matter, stage iii anything. As wbrt has been shown to reduce the likelihood of neurologic death, can we say it's definitive? Otoh, if overall survival is our metric, aren't we just saying it's all palliative?

 

[ramsesthenice]

If it's about survival, then irradiating someone else's prostate is more definitive than treating a gbm, or for that matter, stage iii anything. As wbrt has been shown to reduce the likelihood of neurologic death, can we say it's definitive? Otoh, if overall survival is our metric, aren't we just saying it's all palliative?

In my mind definitive implies curative intent. Palliative treatments can prolong survival, they just are not expected to be curative. Hence, I don’t refer to definitive pancreatic RT. I think primary RT is a better descriptor in settings where RT is the primary local therapy but cure is not the goal.

 

[Ray D. Ayshun]

In my mind definitive implies curative intent. Palliative treatments can prolong survival, they just are not expected to be curative. Hence, I don’t refer to definitive pancreatic RT. I think primary RT is a better descriptor in settings where RT is the primary local therapy but cure is not the goal.

Definition of PALLIATE

to reduce the violence of (a disease); also : to ease (symptoms) without curing the underlying disease; to cover by excuses and apologies; to moderate the intensity of… See the full definition

www.merriam-webster.com

Definition 1:. Treating painful prostate bone met 3 x 10
Definition 2:. Treating low risk prostate 1.8 x 44

 

[ramsesthenice]

Definition of PALLIATE

to reduce the violence of (a disease); also : to ease (symptoms) without curing the underlying disease; to cover by excuses and apologies; to moderate the intensity of… See the full definition

www.merriam-webster.com

Definition 1:. Treating painful prostate bone met 3 x 10
Definition 2:. Treating low risk prostate 1.8 x 44

Someone please let Ray know Scar hacked his account 🙂