Unusual Location PSMA Node

[Haybrant]

53 yo very healthy man with unfav int risk prostate cancer Gleason 4+3 in 12 of 16 targeted biopsy cores PSA 16 ng/ml (was 14 back in November) had a PSMA for staging that shows Suvmax uptake of 4.1 in a small perirectal node (see picture). There was an MRI done prior to the PSMA that shows a very small node there (wasnt called on the MRI read bc it was so small). Patient pretty interested in surgery but surgery did refer to us for discussion first and also noted in tumor board that they likely can not get to the node. Just curious what people think. Looks like an unusual spot for prostate met too, its pretty posterior to the external iliac on the left that I dont think it would have gotten good coverage with standard volumes

---

Members don't see this ad.

 

[Chartreuse Wombat]

53 yo very healthy man with unfav int risk prostate cancer Gleason 4+3 in 12 of 16 targeted biopsy cores PSA 16 ng/ml (was 14 back in November) had a PSMA for staging that shows Suvmax uptake of 4.1 in a small perirectal node (see picture). There was an MRI done prior to the PSMA that shows a very small node there (wasnt called on the MRI read bc it was so small). Patient pretty interested in surgery but surgery did refer to us for discussion first and also noted in tumor board that they likely can not get to the node. Just curious what people think. Looks like an unusual spot for prostate met too, its pretty posterior to the external iliac on the left that I dont think it would have gotten good coverage with standard volumes

As PSMA becomes more widespread this will happen more and more. PSMA is pretty specific and the test is teaching us that much of what we thought we knew about lymph node spread in prostate cancer is wrong. At a referral center I see cases like this once a month at least

 

[HolySmokes]

Since PSMA I have started to see quite a few more mesorectal/perirectal LN mets. I'd be pretty suspicious that it's real.

 

[madchemist89]

Looks real. Might be low presacral.

 

[communitydoc13]

Not a very unusual a spot. Agree with above that perirectal LN (which we do not cover prophylactically ever) also not that uncommon. Right iliac node also concerning.

All this does not necessarily mean that surgery is wrong in a 53 year old BTW. Although patient should be counseled that cure is unlikely and salvage therapy very very likely (with good chance of systemic therapy escalation).

 

[Haybrant]

Not a very unusual a spot. Agree with above that perirectal LN (which we do not cover prophylactically ever) also not that uncommon. Right iliac node also concerning.

All this does not necessarily mean that surgery is wrong in a 53 year old BTW. Although patient should be counseled that cure is unlikely and salvage therapy very very likely (with good chance of systemic therapy escalation).

thanks very helpful yes taken in context of his biopsy and path this makes sense.

So what do you guys think for treatment? Im not a fan of surgery in this case esp if they cant access this node, feel like we should do RT + ADT but he is 53 and does appear to be pretty gung ho surgery based on what urology says. havent spoken with him yet

 

[Ray D. Ayshun]

thanks very helpful yes taken in context of his biopsy and path this makes sense.

So what do you guys think for treatment? Im not a fan of surgery in this case esp if they cant access this node, feel like we should do RT + ADT but he is 53 and does appear to be pretty gung ho surgery based on what urology says. havent spoken with him yet

If nothing else you can tell him the nccn prefers ebrt plus adt plus abi. RP could be said to still be in the guidelines but you'd have to be Clarence Thomas to not have ethical issues doing it.

 

[Palex80]

Is the node within the mesorectal fat or not? It looks quite high to me.

If it's in the mesorectal fat (you could try to match it on the MRI), then the urologists cannot resect it.
If it's not in the mesorectal fat, it's probably too small to be found and outside the normal template anyways.

The next interesting question that pops up is: If you are going to treat this with primary RT, what is your volume?
Will you extend your elective volume along the mesorectum to deliver some dose there too (provided the node is within the mesorectal fat)?

 

[TheWallnerus]

As PSMA becomes more widespread this will happen more and more. PSMA is pretty specific and the test is teaching us that much of what we thought we knew about lymph node spread in prostate cancer is wrong. At a referral center I see cases like this once a month at least

I think the odds are pretty high based on the sensitivity, specificity, and pretest likelihoods PSMA is NOT teaching us this. Especially in a case like this.

 

[medgator]

Not a very unusual a spot. Agree with above that perirectal LN (which we do not cover prophylactically ever) also not that uncommon. Right iliac node also concerning.

All this does not necessarily mean that surgery is wrong in a 53 year old BTW. Although patient should be counseled that cure is unlikely and salvage therapy very very likely (with good chance of systemic therapy escalation).

Pretty close to obturators, sometimes I'll draw generously posterior to those if i can

 

[Chartreuse Wombat]

I think the odds are pretty high based on the sensitivity, specificity, and pretest likelihoods PSMA is NOT teaching us this. Especially in a case like this.

OK let's spell this out. Not mentioned whether Ga68 or Pylarify.

OSPREY (Pylarify) Cohort A Specificity 97.9% for LN

Ga68 from UCLA/UCSF Specificity 95% for LN

I don't know what your pre-test likelihood is but no information on MRI findings in prostate or genomics

Of course this node is not included in a conventional lymphadenectomy so maybe that means the above two studies are bunk.

Going anecdotal now, again I see a case similar to this whether at diagnosis or recurrence following definitive therapy. Perirectal/presacral nodes are more commonly involved than we think they are.

Please let me know what I am missing.

 

[communitydoc13]

If nothing else you can tell him the nccn prefers ebrt plus adt plus abi. RP could be said to still be in the guidelines but you'd have to be Clarence Thomas to not have ethical issues doing it.

I'm not sure on this one. Guy is 53. My guess is that the prostate has a good chance of recapitulating cancer 15 years down the road. At that point, guy is only 68 and salvage is so so tough. No Gleason 5 on biopsy, indicating that the competing risk of early out of control distant progression may not be that high.

I'm not sure that taking it out and doing what is essentially adjuvant (waiting for first detectable PSA for early salvage) treatment with some dose escalation to PSMA PET avid nodes and incorporating Abi or Enza is such a bad option here.

 

[seper]

probably real. I'd radiate and boost

 

[deleted1111261]

seems real to me
i like communitydoc13 approach
take it out, treat adjuvant

but, radiating and boosting reasonable, too. rectum is going to get scorched if doing large volume of adjacent MRE

 

[RadRadRad]

I’ve seen multiple patients with perirectal nodes from prostate cancer. Obviously not common but does happen.
I’ve sent for eus biopsy to prove it before
Wonder if they could biopsy that one ?

 

[Ray D. Ayshun]

I'm not sure on this one. Guy is 53. My guess is that the prostate has a good chance of recapitulating cancer 15 years down the road. At that point, guy is only 68 and salvage is so so tough. No Gleason 5 on biopsy, indicating that the competing risk of early out of control distant progression may not be that high.

I'm not sure that taking it out and doing what is essentially adjuvant (waiting for first detectable PSA for early salvage) treatment with some dose escalation to PSMA PET avid nodes and incorporating Abi or Enza is such a bad option here.

I dunno. Id prefer as much normal t intact pelvic plexus time as possible. Seems more likely sans surgery

 

[RadOncDoc21]

What, rad oncs with no consensus on treatment recommendations? We haven’t even got started with the dose and fractionation arguments. Color me surprised!

 

[TheWallnerus]

OK let's spell this out. Not mentioned whether Ga68 or Pylarify.

OSPREY (Pylarify) Cohort A Specificity 97.9% for LN

Ga68 from UCLA/UCSF Specificity 95% for LN

I don't know what your pre-test likelihood is but no information on MRI findings in prostate or genomics

Of course this node is not included in a conventional lymphadenectomy so maybe that means the above two studies are bunk.

Going anecdotal now, again I see a case similar to this whether at diagnosis or recurrence following definitive therapy. Perirectal/presacral nodes are more commonly involved than we think they are.

Please let me know what I am missing.

I didn’t know specificity that high, but you’re missing sensitivity; both values I would need for a PPV… and I need us to make some guesses for pretest probability. We have negative conventional imaging….

 

[Chartreuse Wombat]

I didn’t know specificity that high, but you’re missing sensitivity; both values I would need for a PPV… and I need us to make some guesses for pretest probability. We have negative conventional imaging….

Sensitivity is 40% (low)

 

[Palex80]

I'm not sure that taking it out and doing what is essentially adjuvant (waiting for first detectable PSA for early salvage) treatment with some dose escalation to PSMA PET avid nodes and incorporating Abi or Enza is such a bad option here.

"Taking it out" will be challenging though.
A few centers have tried PSMA-guided surgery of nodes, but the expertise is limited.

 

[communitydoc13]

"Taking it out" will be challenging though.
A few centers have tried PSMA-guided surgery of nodes, but the expertise is limited.

Not talking about taking out the nodes. Leave those there. Way outside of typical nodal dissection.

If PSA becomes undetectable, high likelihood nodes are false positive (unlikely that this is the case IMO).

If PSA remains detectable, arrange salvage treatment in reasonable timeframe. You have made local recurrence very unlikely over the lifetime of a 53 y/o. You may have impacted the natural history of the disease favorably.

Agree, that non-surgical management also appropriate (and would be absolutely preferred for the 65+ crowd).

 

[FindMeOnTheLinks]

Would you believe a negative eus biopsy? If yes, send for eus biopsy

 

[madchemist89]

Treat prostate, seminal vehicles, nodes. Boost PSMA positive node add long term ADT. Trimodality therapy will only increase toxicity.

 

[TheWallnerus]

Sensitivity is 40% (low)

Sensitivity is the kicker here; highly specific tests can rule things in, but specificity doesn’t exist in a vacuum IRL. If you grant me a 10% probability a patient such as presented with the clinical factors given has a truly positive perirectal LN, a positive perirectal LN here by PSMA has a PPV barely better than a coin flip. And we are going to boost that with high dose RT in a touchy location? If the pretest likelihood is 9% or less, a coin flip would have better PPV than a PSMA.

 

[Chartreuse Wombat]

Umm...PPV depends on sensitivity AND prevalence.

If the prevalence is 20% then

Much more than a coin flip.

Incidentally some people electively irradiate nodes with a 15-20% of involvement. I don't believe in ENI but many do

So which is closer to the truth? 10% prevalence, 20% prevalence? 1% prevalence?

One could go to their favorite nomogram and come up with a LN+ prevalence.

Boomers might choose the simple but outdated Roach formula 2/3PSA + ((GS-6)*10) which will get you around 15% but it is likely that the perirectal lymph nodes were not sampled in the patients whose data are behind the nomogram.

Oy!!!

 

[TheWallnerus]

Umm...PPV depends on sensitivity AND prevalence.

If the prevalence is 20% then

View attachment 369514
Much more than a coin flip.

Incidentally some people electively irradiate nodes with a 15-20% of involvement. I don't believe in ENI but many do

So which is closer to the truth? 10% prevalence, 20% prevalence? 1% prevalence?

One could go to their favorite nomogram and come up with a LN+ prevalence.

Boomers might choose the simple but outdated Roach formula 2/3PSA + ((GS-6)*10) which will get you around 15% but it is likely that the perirectal lymph nodes were not sampled in the patients whose data are behind the nomogram.

Oy!!!

If one out of five Gleason 4+3/PSA 16 prostate cancer patients have positive perirectal lymph nodes we seriously need to change current standard ENI contours/volumes… we are missing tons of disease. I thought a one in ten chance was generous!

 

[Chartreuse Wombat]

If one out of five Gleason 4+3/PSA 16 prostate cancer patients have positive perirectal lymph nodes we seriously need to change current standard ENI contours/volumes… we are missing tons of disease. I thought a one in ten chance was generous!

I don't know the answer about the prevalence in this case. I am surprised by the enormous heterogeneity of UIR. Gleason Grade is/was helpful but AI is making it clear that there is lots of information in pathology/genomics that has escaped human perception.

PSMA for better or for worse is leading to more questions than answers (as do all new technologies).

 

[medgator]

If one out of five Gleason 4+3/PSA 16 prostate cancer patients have positive perirectal lymph nodes we seriously need to change current standard ENI contours/volumes… we are missing tons of disease. I thought a one in ten chance was generous!

it literally is behind/posterior to the obturator volumes, even more obvious post-prostatectomy IMO, i try to sneak some of it in when reasonable

 

[communitydoc13]

If one out of five Gleason 4+3/PSA 16 prostate cancer patients have positive perirectal lymph nodes we seriously need to change current standard ENI contours/volumes… we are missing tons of disease. I thought a one in ten chance was generous!

In this case, high volume, Gleason 4+3=7 with PSA>10, traditional nomograms will indicate high likelihood of some nodal involvement per surgical series.

Regarding nodes in "weird places". I agree with @Chartreuse Wombat that PSMA PET is telling us something.

A CT or MRI normal node, that harbors metastatic disease outside of typical treatment volumes, may take ages to manifest as a PSA failure after XRT/ADT, and while our numbers for disease specific survival are excellent at timepoints like 10-15 years in patients like this (79% DFS at 15 years after sx per historic MSKCC nomogram data), the likelihood of durable biochemical control after surgery is very low (24% at 10 years). Typically, our biochemical control numbers (with a different standard that frankly allows for smoldering residual or metastatic disease to percolate prior to designating failure) sort of follow the surgical numbers. It is possible that many of these failures are due to regional disease outside of treatment volumes.

Just saying, maybe not as uncommon as we think. In this setting, there is another focus concerning for regional nodal metastases IMO. This again would increase the likelihood of nodal involvement in "weird places". ( I am not going to be electively treating perirectal lymph nodes ever.)

 

[RadOncDoc21]

In this case, high volume, Gleason 4+3=7 with PSA>10, traditional nomograms will indicate high likelihood of some nodal involvement per surgical series.

Regarding nodes in "weird places". I agree with @Chartreuse Wombat that PSMA PET is telling us something.

A CT or MRI normal node, that harbors metastatic disease outside of typical treatment volumes, may take ages to manifest as a PSA failure after XRT/ADT, and while our numbers for disease specific survival are excellent at timepoints like 10-15 years in patients like this (79% DFS at 15 years after sx per historic MSKCC nomogram data), the likelihood of durable biochemical control after surgery is very low (24% at 10 years). Typically, our biochemical control numbers (with a different standard that frankly allows for smoldering residual or metastatic disease to percolate prior to designating failure) sort of follow the surgical numbers. It is possible that many of these failures are due to regional disease outside of treatment volumes.

Just saying, maybe not as uncommon as we think. In this setting, there is another focus concerning for regional nodal metastases IMO. This again would increase the likelihood of nodal involvement in "weird places". ( I am not going to be electively treating perirectal lymph nodes ever.)

Agree with this, it’s almost like what’s the point of a PSMA scan if we are not going to believe what it shows.

Some would also argue don’t ask don’t tell and not order one. Could the use of ADT irradicated this possible area of distant disease-?

If anything, this likely means you’re going to have to treat the pelvis and that node or at the very least biopsy it because something showed up on the PSMA-PET. Rather this came as a benefit to the patient (catching possible areas of disease) or possible harming the patient (over treating causing side effects) will have to be reviewed based on the indications for and against ordering a PSMA scan for these patients.

For what it’s worth, I don’t usually order PSMA-PET for intermediate risk prostate cancer and haven’t been treating the nodes either unless they decline or unable to receive ADT. Even then, I’m not sure we routinely would order a PSMA scan. Maybe in the setting of unfavorable risk, I might start changing my tune.

 

[Palex80]

This man needs 3 years of ADT and 2 years of ABIRATERONE on top whatever volume all of you "radiologists" want to zap!

 

[sirspamalot]

PSMA for better or for worse is leading to more questions than answers (as do all new technologies).

THIS. We are making stuff up and extracting stuff out of thin air. No clue if a) its real disease b) that it makes any difference if its treated with XRT or not.

How many pre-PSMA era patients had this stuff and what % of them (who had no targeted treatment) resulted in worse outcome? NFC.

You can do whatever you want. The uro guys get patients cranked up about surgery - zero proof its any better. Me? I'd say radiation (I am generous about treating nodes either by unfav or %roachlike) and include a zap to the PSMA node of uncertainty (esp if it can't be negatively biopsied). But we are in uncharted waters...

I don't have PSMA pet at my facility, so I can't open that can of worms. Maybe its better that way.

 

[DoctwoB]

This situation has been coming up more and more. Tumor board today had 3 "what to do about this PSMA PET scan results"

Common questions/issues
Is it really positive? what to do with borderline SUVmax
If it is positive, will treating it effect course of disease? Will changing our local therapy based on presumed mets negatively effect local and future distant control?


My take:
1. I don't order PSMA PET in the up front setting unless high risk due to low pre-test probability making it less useful.
2. Until we have more data, we should be cautious about making sweeping changes to our treatment plans based on results.

Take this case. The node may be involved or it may be a false positive. SUVmax of 4 is pretty weak, especially if the prostate SUV max is closer to 15. Pre-test probability is low enough that even with high specificity there is a good chance its false, especially if the SUVmax doesn't blow you away. My inclination would be to treat it as I normally would, which in this case sounds like surgery, with the possible addition of resecting the node if it is accessible. Then you can see what the PSA does, and if it never becomes undetectable or recurs rapidly you have a likely reason for it and you salvage with XRT. Up front XRT with ADT or trimodal therapy is also totally reasonable. I defer to you guys if boosting the node is worth the potential morbidity in that setting.

Edit: FWIW I think that node is more likely to be pre-sacral then mesorectal, and could be potentially accessible surgically, its a similar way that we expose the sacrum in a robotic sacropcolpopexy.

 

[Palex80]

My take:
1. I don't order PSMA PET in the up front setting unless high risk due to low pre-test probability making it less useful.
2. Until we have more data, we should be cautious about making sweeping changes to our treatment plans based on results.

Then why order the PSMA-PET anyway?

Some of the older folks here may recall what happened when we incorporated FDG-PET-CT in our practice around 15-20 years ago.
Suddenly, every second patient was getting a colonoscopy or an ultrasound of the thyroid gland to clarify some unusualy FDG-uptake.

 

[DoctwoB]

Then why order the PSMA-PET anyway?

Some of the older folks here may recall what happened when we incorporated FDG-PET-CT in our practice around 15-20 years ago.
Suddenly, every second patient was getting a colonoscopy or an ultrasound of the thyroid gland to clarify some unusualy FDG-uptake.

I usually don't!.

In the very high risk setting, I get one, but more for the purpose of possible treatment escalation, usually in younger patients.

Negative? you get your usual trimodal or ADT + XRT or surgery with possible future salvage.

Positive low volume? Maybe we do the above but also sbrt your one or two bone lesions or boost your node.

Positive high volume? these are the guys where you probably would have seen this on the CT/bone scan anyways, and they end up getting treated similarly.

 

[maxxor]

53 yo very healthy man with unfav int risk prostate cancer Gleason 4+3 in 12 of 16 targeted biopsy cores PSA 16 ng/ml (was 14 back in November) had a PSMA for staging that shows Suvmax uptake of 4.1 in a small perirectal node (see picture). There was an MRI done prior to the PSMA that shows a very small node there (wasnt called on the MRI read bc it was so small). Patient pretty interested in surgery but surgery did refer to us for discussion first and also noted in tumor board that they likely can not get to the node. Just curious what people think. Looks like an unusual spot for prostate met too, its pretty posterior to the external iliac on the left that I dont think it would have gotten good coverage with standard volumes

What do you call “positive” based on the suv max alone?

Suvmax in isolation is a useless value.

What was the suvmean liver and what was the suvmean parotid? How ancient of a scanner is it? Does it have resolution recovery reconstruction or is it a 20 year old battle axe that probably shouldn’t be doing psma scans?

i think it’s positive. I don’t think presacral nodes are “atypical”. But I’m just the rad.

 

[RadOncDoc21]

I say treat half the node… split the difference!

 

[evilbooyaa]

Lots of presacral/mesorectal LNs popping up on PSMA PET/CTs. Looka t any post-salvage RT patterns of failure analysis - posterior is a common site of recurrence. We historically had no good means of identifying LNs in that region. It is a failure site that is not routinely covered, which is honestly probably a reasonable question to ask and why

I see no rationale for surgery in this location. Patient will tolerate gross disease dosing to that region just fine given it's abutting the rectum (like the prostate is). Respect dosimetry and push hard otherwise.

I've done gross disease dose to the gross LN and cover mesorectum 2cm sup and inf similar to a rectal case to 45Gy ENI and patients have tolerated it just fine. TBD on whether we avoid recurrence in the mesorectum. Unlikely to ever determine whether ENI to the mesorectum to 45Gy is actually necessary.

I don't routinely order PSMA PET/CTs on IR patients, but if someone was to get one and then completely ignore this result, that someone would be kind of a dummy.

Consider biopsy at least if you're going to treat as if it is negative...

 

[communitydoc13]

Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings - Cancer Imaging

PSMA PET imaging was originally used to assess biochemical recurrence of prostate cancer (PCa), but its clinical use was promptly extended to detection, staging and therapy response assessment. The expanding use of PSMA PET worldwide has also revealed PSMA ligand uptake in diverse nonprostatic...

cancerimagingjournal.biomedcentral.com

Great paper. Check out ganglia uptake. Sacral ganglia uptake can mimic a small presacral node. Epigastric and celiac ganglia could mimic low volume retroperitoneal involvement.

 

[sirspamalot]

Wild goose chase: confirmed

 

[TheWallnerus]

Wild goose chase: confirmed

Not confirmed, but it’s in the differential!

 

[seper]

Thanks. Very interesting.
I just had a case of PSMA + liver lesion, which turned to be an incidental, curable HCC. Medoncs are writing it up.

Nonprostatic diseases on PSMA PET imaging: a spectrum of benign and malignant findings - Cancer Imaging

PSMA PET imaging was originally used to assess biochemical recurrence of prostate cancer (PCa), but its clinical use was promptly extended to detection, staging and therapy response assessment. The expanding use of PSMA PET worldwide has also revealed PSMA ligand uptake in diverse nonprostatic...

cancerimagingjournal.biomedcentral.com

Great paper. Check out ganglia uptake. Sacral ganglia uptake can mimic a small presacral node. Epigastric and celiac ganglia could mimic low volume retroperitoneal involvement.

View attachment 370063

 

[TheWallnerus]

Thanks. Very interesting.
I just had a case of PSMA + liver lesion, which turned to be an incidental, curable HCC. Medoncs are writing it up.

Does this mean some other things besides prostate express prostate specific antigen

Should we start calling it prostate nonspecific antigen… prostate sensitive antigen…

 

[Palex80]

PSA is not PSMA.

 

[TheWallnerus]

PSA is not PSMA.

Was listening to Cypress Hill when I wrote that, sorry

 

[sirspamalot]

Oops.

 

[evilbooyaa]

Does this mean some other things besides prostate express prostate specific antigen

Should we start calling it prostate nonspecific antigen… prostate sensitive antigen…

Recently had a case of PSMA uptake in the brain of a prostate cancer patient - turns out he has a h/o of treated meningioma - this is documented in the literature.

Meningioma uptake of 68Gallium-PSMA-11 as a pitfall on positron emission tomography/computer tomography - PubMed

Prostate cancer is the most common malignancy in men with high incidence of recurrence following treatment. Biochemical recurrence, as indicated by rising PSA levels following successful treatment of the primary disease, is a frequent encounter in routine clinical practice...

pubmed.ncbi.nlm.nih.gov