Rationale for timing of adjuvant RT after surgery: breast and prostate

[RadOncBeamer]

I'm seeing someone, Gleason 4+5=9, pre-tx PSA 8. Upfront PSMA showed uptake in a mesorectal and left iliac node. Went for surgery with prostatectomy with lymph node dissection. pT3bN1, margins neg, 1/17 LN. Post-op PSA down to 3 (never undetectable). Post-op PSMA PET showed residual uptake in a single left iliac node, no distant disease. He was started on ADT + zytiga and due to multiple issues (continence, logistical hurdles, etc) I'm only seeing him now 9 months later. PSA is now undetectable.

So I understand that in breast and prostate, we typically have thresholds (which may vary between provider) for when we would consider adjuvant radiation. For breast, I think we often try and start patients within 3 months but may allow up to 6 months. For prostate, if a patient meets indications for adjuvant RT (less so in the radicals/raves era) we start them within 6 months or when continence is recovered to its maximal ability.

My question is - the rationale for not delaying RT too long after surgery is the presumption that residual disease will start to grow and efficacy of RT is diminished. However, if someone is placed on hormone therapy (ADT for prostate or AI for breast), then wouldn't it make sense that regrowth will be inhibited? If so, would it be reasonable to start someone 9 months or 12 months after surgery if they've been on hormone therapy, as the ADT itself is cytostatic, as opposed to RT which is cytotoxic.

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[TheWallnerus]

I'm seeing someone 9 months after radical prostatectomy whose post-op PSMA PET showed residual uptake in the pelvic nodes, no distant disease. He was started on ADT + zytiga and due to multiple issues (continence, patient logistics, etc) I'm only seeing him now. PSA is now undetectable.

So I understand that in breast and prostate, we typically have thresholds (which may vary between provider) for when we would consider adjuvant radiation. For breast, I think we often try and start patients within 3 months but may allow up to 6 months. For prostate, if a patient meets indications for adjuvant RT (less so in the radicals/raves era) we start them within 6 months or when continence is recovered to its maximal ability.

My question is - the rationale for not delaying RT too long after surgery is the presumption that residual disease will start to grow and efficacy of RT is diminished. However, if someone is placed on hormone therapy (ADT for prostate or AI for breast), then wouldn't it make sense that regrowth will be inhibited? If so, would it be reasonable to start someone 9 months or 12 months after surgery if they've been on hormone therapy, as the ADT itself is cytostatic, as opposed to RT which is cytotoxic.

Can you let us know all the particulars of the prostate cancer itself, grade, etc

 

[elementaryschooleconomics]

I'm seeing someone 9 months after radical prostatectomy whose post-op PSMA PET showed residual uptake in the pelvic nodes, no distant disease. He was started on ADT + zytiga and due to multiple issues (continence, patient logistics, etc) I'm only seeing him now. PSA is now undetectable.

So I understand that in breast and prostate, we typically have thresholds (which may vary between provider) for when we would consider adjuvant radiation. For breast, I think we often try and start patients within 3 months but may allow up to 6 months. For prostate, if a patient meets indications for adjuvant RT (less so in the radicals/raves era) we start them within 6 months or when continence is recovered to its maximal ability.

My question is - the rationale for not delaying RT too long after surgery is the presumption that residual disease will start to grow and efficacy of RT is diminished. However, if someone is placed on hormone therapy (ADT for prostate or AI for breast), then wouldn't it make sense that regrowth will be inhibited? If so, would it be reasonable to start someone 9 months or 12 months after surgery if they've been on hormone therapy, as the ADT itself is cytostatic, as opposed to RT which is cytotoxic.

At the end of the day, it comes down to "evidence".

From a logical standpoint: I completely agree with you.

However, there are A LOT of things we do which could be "done better", but there's limited or no data to support taking such action at this time.

My favorite example is endocrine therapy. You used to have to take it for 10 years. Now it's 5. Could the same benefit be seen with...2 years? Will that trial ever be done?

The evolution of technology also VASTLY outpaces our clinical trials and long-term results. That stupid single shot prostate paper published the other day is a great example. 18 months for prostate? Give me a break. That's HIFU territory.

Unfortunately, the only solution we really have for these "logical conundrums" is to...design and execute the trials ourselves. And wait. And wait.

I would be very interested in "best timing of adjuvant XRT for breast", for example. However, if I were to begin designing that trial RIGHT THIS VERY MINUTE...I doubt I would have 5- or 10-year data on that trial before I retire.

Yay medicine!

 

[ramsesthenice]

With prostate it’s a little easier. If the PSA is undetectable (or close to it) then yes, chances are almost certain it’s in check and probably no harm came from waiting. Regardless of how long it’s been since surgery, I personally like to wait a couple months to make sure they get the expected biochemical response to whatever they are trying and are happy with it.

 

[Palex80]

I'm seeing someone, Gleason 4+5=9, pre-tx PSA 8, pT3bN1, 9 months after radical prostatectomy whose post-op PSMA PET showed residual uptake in the pelvic nodes, no distant disease.

I am sorry, but could you be a bit more specific?

So, the patient had a radical prostatectomy with pelvic lymphadenectomy.

1. How many nodes were removed and how many were affected? What was the margin on the prostate bed?

2. Did he get the PSMA-PET-CT afterwards because he the PSA did not drop below detectable levels or was this a PSA recurrence later on? When was the PET-CT performed in these 9 months between surgery and now?

3. How many nodes are visible on the PET-CT?

My question is - the rationale for not delaying RT too long after surgery is the presumption that residual disease will start to grow and efficacy of RT is diminished. However, if someone is placed on hormone therapy (ADT for prostate or AI for breast), then wouldn't it make sense that regrowth will be inhibited? If so, would it be reasonable to start someone 9 months or 12 months after surgery if they've been on hormone therapy, as the ADT itself is cytostatic, as opposed to RT which is cytotoxic.

I recall this analysis that is looked into this issue.

Neoadjuvant hormone therapy and external-beam radiation for localized high-risk prostate cancer: the importance of PSA nadir before radiation - PubMed

Improved bDFS in patients with high-risk prostate cancer was associated with lower initial PSA level, lower Gleason score, and lower preradiation PSA level. The duration of NAHT did not have an impact on outcomes, but the preradiation PSA was an important predictor of bDFS in high-risk patients.

pubmed.ncbi.nlm.nih.gov

 

[RadRadRad]

This is salvage not adjuvant. Pet showed residual disease.
Prostate has lots of data in the intact setting that you can be on adt for 2 mo, 3 mo, 5mo or maybe even longer prior to starting radiation with good results. I believe Canada and maybe Australia have rct with much longer duration of adt prior to rt than the USA standard of 2 mo.
Extrapolating from those in salvage setting makes sense.
This patient needs rt unless you don’t believe in rt for node positive.

 

[RadRadRad]

Final report of multicenter Canadian Phase III randomized trial of 3 versus 8 months of neoadjuvant androgen deprivation therapy before conventional-dose radiotherapy for clinically localized prostate cancer - PubMed

A longer period of NHT before standard-dose RT did not alter the patterns of failure when combined with 66-Gy RT. High-risk patients in the 8-month arm had significant improvement in the 5-year disease-free survival rate.

pubmed.ncbi.nlm.nih.gov

3mo vs 8 mo neoadj adt

Again this is intact but no reason to think it would be different in salvage

 

[ramsesthenice]

Then we all have the better late than never experiences. IE, old time urologists (at least in my neck of the woods) watches the PSA rise for a couple of years, then eventually starts ADT and at some point the patient ends up self referring to me. Even then you can get decent control with salvage radiation. I wouldn’t use these kinds of cases to suggest timing is entirely superfluous, but I personally have no thresholds when someone shows up. If they have no evidence of metastatic disease, I will consider treating.

Now just to be extremely clear, we are talking about salvage. You said adjuvant. We do adjuvant for breast but very few of us are routinely doing true adjuvant for prostate. I think the only scenario in which I do “adjuvant” is if there are positive nodes on pathology and the post op PSA is undetectable. Though I’m not sure if that’s technically adjuvant or not based on study definitions.

 

[medgator]

Then we all have the better late than never experiences. IE, old time urologists (at least in my neck of the woods) watches the PSA rise for a couple of years, then eventually starts ADT and at some point the patient ends up self referring to me. Even then you can get decent control with salvage radiation. I wouldn’t use these kinds of cases to suggest timing is entirely superfluous, but I personally have no thresholds when someone shows up. If they have no evidence of metastatic disease, I will consider treating.

Now just to be extremely clear, we are talking about salvage. You said adjuvant. We do adjuvant for breast but very few of us are routinely doing true adjuvant for prostate. I think the only scenario in which I do “adjuvant” is if there are positive nodes on pathology and the post op PSA is undetectable. Though I’m not sure if that’s technically adjuvant or not based on study definitions.

I think it is within 4-6 months. Could argue it isn't adjuvant though when the PSA never went undetectable, had/have +margins/svi/ece

 

[drowsy12]

I'm a bit confused by the question in this setting, because in prostate, we regularly wait years before treating sometimes - with salvage. So it's kind of normal here.

I think you can very reasonably choose to treat or continue watching (I would treat for node-positive) without worrying one iota about time since surgery. It's prostate not HNSCC or adjuvant breast.

 

[ramsesthenice]

I think it is within 4-6 months. Could argue it isn't adjuvant though when the PSA never went undetectable, has have +margins/svi/ece

I would strongly argue this is not adjuvant. I know there is no clear line, but in my mind, if the PSA is detectable after surgery, it ain't adjuvant. I whole-heartedly believe this is why the SWOG adjuvant trial showed a positive survival benefit. The PSA cutoff was not zero and I think something like a third of the patients had a detectable PSA. In other words, it wasn't really an adjuvant trial.

 

[ramsesthenice]

So on a related point, what are folks doing for negative PSA but positive pathologic nodes? This is probably the only routine point of contention that I have with our urologists. Its hard for me to imaging that just observing these folks is a good idea regardless of the PSA. In my mind, this should at the very least buy systemic therapy (though I argue for systemic therapy and ADT). I understand the argument that we don't know intervening before the PSA becomes detectable changes the long-term disease course. But unlike prostate only disease, we know in this setting its already second echelon and patterns of recurrence are unclear. Further, we have always considered N+ disease as systemic for prostate cancer, so I am a little unclear why the PSA (which is mostly a measure of disease burden) changes that equation.

 

[Mandelin Rain]

So on a related point, what are folks doing for negative PSA but positive pathologic nodes? This is probably the only routine point of contention that I have with our urologists. Its hard for me to imaging that just observing these folks is a good idea regardless of the PSA. In my mind, this should at the very least buy systemic therapy (though I argue for systemic therapy and ADT). I understand the argument that we don't know intervening before the PSA becomes detectable changes the long-term disease course. But unlike prostate only disease, we know in this setting its already second echelon and patterns of recurrence are unclear. Further, we have always considered N+ disease as systemic for prostate cancer, so I am a little unclear why the PSA (which is mostly a measure of disease burden) changes that equation.

If healthy, I think there is plenty of evidence to suggest early intensive treatment (Pelvic PORT, multiple systemics) is better than delayed or ADT alone.

 

[communitydoc13]

So on a related point, what are folks doing for negative PSA but positive pathologic nodes? This is probably the only routine point of contention that I have with our urologists. Its hard for me to imaging that just observing these folks is a good idea regardless of the PSA. In my mind, this should at the very least buy systemic therapy (though I argue for systemic therapy and ADT). I understand the argument that we don't know intervening before the PSA becomes detectable changes the long-term disease course. But unlike prostate only disease, we know in this setting its already second echelon and patterns of recurrence are unclear. Further, we have always considered N+ disease as systemic for prostate cancer, so I am a little unclear why the PSA (which is mostly a measure of disease burden) changes that equation.

Treating Primary Node-Positive Prostate Cancer: A Scoping Review of Available Treatment Options

The best way to treat patients with prostate cancer who have positive lymph nodes is not clear. However, recent studies have suggested that intensifying treatment may help these patients and potentially cure their cancer. This review summarises the existing ...

www.ncbi.nlm.nih.gov

Some node positive patients will have durable control after surgery (we are not talking about our gross node positive folks here).

I've had a a couple patients with incidental positive node at time of surgery who have had durable biochemical control (now years) and no adjuvant treatment (per me). I'm just waiting for any bump in PSA to administer combined modality therapy.

PSA is uniquely sensitive.

GG5 disease I do not wait.

 

[TheWallnerus]

I'm seeing someone, Gleason 4+5=9, pre-tx PSA 8, pT3bN1, 9 months after radical prostatectomy whose post-op PSMA PET showed residual uptake in the pelvic nodes, no distant disease. He was started on ADT + zytiga and due to multiple issues (continence, logistical hurdles, etc) I'm only seeing him now. PSA is now undetectable.

So I understand that in breast and prostate, we typically have thresholds (which may vary between provider) for when we would consider adjuvant radiation. For breast, I think we often try and start patients within 3 months but may allow up to 6 months. For prostate, if a patient meets indications for adjuvant RT (less so in the radicals/raves era) we start them within 6 months or when continence is recovered to its maximal ability.

My question is - the rationale for not delaying RT too long after surgery is the presumption that residual disease will start to grow and efficacy of RT is diminished. However, if someone is placed on hormone therapy (ADT for prostate or AI for breast), then wouldn't it make sense that regrowth will be inhibited? If so, would it be reasonable to start someone 9 months or 12 months after surgery if they've been on hormone therapy, as the ADT itself is cytostatic, as opposed to RT which is cytotoxic.

Are you treating? I would treat. Not that it makes a huge difference, how old is patient, and what has his "hormone experience" been like.

 

[RadOncBeamer]

Thanks everyone for the responses as well as clarification on the terminology. I edited the original post to provide a bit more detail. I did decide to treat, I just wanted to make sure it made sense since I had never treated someone this far out from surgery. In the normal adjuvant setting, we usually wait up to 6 months post-op, beyond which patients may derive less of a benefit. Meanwhile for salvage, the trigger is successive PSA rises or PSA rise to >= 0.2, but his PSA has been undetectable for almost 9 months on ADT + zytiga. This did not quite fit either scenario.

Semantics: I was under the impression that adjuvant vs salvage was a decision made at the time of surgery based on pathologic factors. E.g. regardless of whether there's residual disease, or PSA is detectable, RT is considered adjuvant if the goal is to eradicate microscopic (or in rare cases macroscopic) disease that may be remaining after surgery. Similar to head and neck, we call it adjuvant regardless of whether an R0 or R2 (gross disease) resection occurs. Salvage to me usually means treatment at the time of disease progression, which in the prostate world means multiple PSA rises.

 

[TheWallnerus]

Thanks everyone for the responses as well as clarification on the terminology. I edited the original post to provide a bit more detail. I did decide to treat, I just wanted to make sure it made sense since I had never treated someone this far out from surgery. In the normal adjuvant setting, we usually wait up to 6 months post-op, beyond which patients may derive less of a benefit. Meanwhile for salvage, the trigger is successive PSA rises or PSA rise to >= 0.2, but his PSA has been undetectable for almost 9 months on ADT + zytiga. This did not quite fit either scenario.

Semantics: I was under the impression that adjuvant vs salvage was a decision made at the time of surgery based on pathologic factors. E.g. regardless of whether there's residual disease, or PSA is detectable, RT is considered adjuvant if the goal is to eradicate microscopic (or in rare cases macroscopic) disease that may be remaining after surgery. Similar to head and neck, we call it adjuvant regardless of whether an R0 or R2 (gross disease) resection occurs. Salvage to me usually means treatment at the time of disease progression, which in the prostate world means multiple PSA rises.

I would call this adjuvant. Just like in the spirit of STAMPEDE we shouldn't use PSMA results to make a call that conventional imaging didn't find, I wouldn't let residual PSMA uptake in the nodes (if CT and MRI are negative or equivocal) after the surgery make this be "salvage." Which you're right is total semantics. I let this paper from D'Amico a few years back take up space in my brain re: the ongoing (ongoing for me, anyways) salvage vs adjuvant debate.

 

[ramsesthenice]

I would call this adjuvant. Just like in the spirit of STAMPEDE we shouldn't use PSMA results to make a call that conventional imaging didn't find, I wouldn't let residual PSMA uptake in the nodes (if CT and MRI are negative or equivocal) after the surgery make this be "salvage." Which you're right is total semantics. I let this paper from D'Amico a few years back take up space in my brain re: the ongoing (ongoing for me, anyways) salvage vs adjuvant debate.

Wait. If we shouldn't use PSMA to make a call that conventional imaging didn't find, then why order the test at all? One of the strongest rationales for using PYL scans is the high sensitivity for metastatic nodes that are below conventional size criteria. Especially in the setting of a non-zero and rising post-operative PSA.

FWIW, I don't completely disagree with you in all settings. I am still unconvinced we should be routinely getting them in some settings like run of the mill unfavorable intermediate risk patients with an intact prostate. Most of our urologists are getting them as initial staging for almost all of these subjects and offhand I can't recall a time it clearly argued we should change management in this specific instance. Though I can remember many where "indeterminate" findings clouded the picture that were ultimately ignored. Or folks ended up getting long-term ADT that they probably didn't need.

 

[TheWallnerus]

Wait. If we shouldn't use PSMA to make a call that conventional imaging didn't find, then why order the test at all?

Tough question. Order it for comfort?, order it for prognostic value?... just in this case I would not feel comfortable making a CHANGED treatment decision on the basis of a PET. To quote STAMPEDE: "Caution will be required in extrapolating these results to patients imaged with more sensitive techniques (eg, PSMA PET). For example, patients with low metastatic burden on conventional imaging should not be denied prostate radiotherapy because they have additional lesions identified on a PET scan." In this case, what if the node had been high para-aortic? Would we give 80 Gy in 40 fx to the prostate, 55 in 20, or 36 in 6? The 80/40 is likely to cure him if the PET was a false positive. The 55/20 or 36/6... not so much curative. But helpful if metastatic! Dilemmas.

 

[CaesarRO]

Tough question. Order it for comfort?, order it for prognostic value?... just in this case I would not feel comfortable making a CHANGED treatment decision on the basis of a PET. To quote STAMPEDE: "Caution will be required in extrapolating these results to patients imaged with more sensitive techniques (eg, PSMA PET). For example, patients with low metastatic burden on conventional imaging should not be denied prostate radiotherapy because they have additional lesions identified on a PET scan." In this case, what if the node had been high para-aortic? Would we give 80 Gy in 40 fx to the prostate, 55 in 20, or 36 in 6? The 80/40 is likely to cure him if the PET was a false positive. The 55/20 or 36/6... not so much curative. But helpful if metastatic! Dilemmas.

... But I think there are at least two studies out there showing that PSMA PET changes the treatment plan anywhere from 1/3 to 1/2 the time.

I think the key is to not exclude patients from curative intent treatment in oligo-settings.

 

[TheWallnerus]

... But I think there are at least two studies out there showing that PSMA PET changes the treatment plan anywhere from 1/3 to 1/2 the time.

Yes, but that data is kind of circular logic thinking... if you think about it... to suggest PSMA PET has led us to a beneficial treatment choice change, versus neutral, vs unbeneficial. (Like the Decipher reps who tell me how often Decipher changes treatment choices, and what a wonderful boon that is for patients, etc.) Is there data showing that after PSMA PET findings people were randomized into cohorts where the PSMA PET was not allowed to affect treatment choice, and where it was allowed, and then compared outcomes between the groups?

I think the key is to not exclude patients from curative intent treatment in oligo-settings.

Or to exclude patients from curative intent treatment in settings that would have been called curative 10 years ago, but are called M1 and oligo today. E.g., I remember someone asking on Twitter about a year ago what to do with a Gleason 4+4 patient who had a left axillary node on PSMA PET, negative elsewhere, all other imaging negative.

 

[ramsesthenice]

Tough question. Order it for comfort?, order it for prognostic value?... just in this case I would not feel comfortable making a CHANGED treatment decision on the basis of a PET. To quote STAMPEDE: "Caution will be required in extrapolating these results to patients imaged with more sensitive techniques (eg, PSMA PET). For example, patients with low metastatic burden on conventional imaging should not be denied prostate radiotherapy because they have additional lesions identified on a PET scan." In this case, what if the node had been high para-aortic? Would we give 80 Gy in 40 fx to the prostate, 55 in 20, or 36 in 6? The 80/40 is likely to cure him if the PET was a false positive. The 55/20 or 36/6... not so much curative. But helpful if metastatic! Dilemmas.

I see what you are saying. Its much more nuanced than it first read and gets to what I was also discussing. This has been an interesting problem. The strengths and weaknesses of these tests is well documented but I have certainly seen many a case where even though the formal read clearly called some PET lesions indeterminate, the payors consider all PET positive lesions metastases and if it adds up to more than 3 deny radiation for anything asymptomatic. It presents quite the dilemma. Some amount of the time, they might reasonably change management. But, if bad actors insist on unscrupulously interpreting them, they may have a higher risk of earning a denial or inappropriately changing treatment.

 

[Chartreuse Wombat]

A few points.

In general PSMA is specific but not that sensitive (in high risk patients PSMA was negative in 40% with path N+ disease)

The endpoint of "changes treatment choices" is a horrible endpoint.

The real issue is whether the findings of the test lead to improved outcomes.

The closest we have is the EMPIRE-1 study that used F18-fluciclovine (not PSMA) and found improved biochemical outcomes in the group in whom the PET was used to define salvage therapy.

EMPIRE-1: Randomized Trial Comparing Conventional- vs Conventional plus Fluciclovine (18F) PET/CT Imaging-Guided Post-Prostatectomy Radiotherapy for Prostate Cancer

Molecular imaging is increasingly used to guide prostate cancer decisions and treatment planning. The specific aim was to evaluate the role of fluciclovine ([18] F) PET {positron emission tomography}/CT{computed tomography} [PET] in improving cancer control ...

www.ncbi.nlm.nih.gov

Biochemical outcomes are not great either. EMPIRE-2 will compare F18 Fluciclovine to Ga68 PSMA

PSMA has become ubiquitous. Stage migration has reared its head again.

 

[TheWallnerus]

A few points.

In general PSMA is specific but not that sensitive (in high risk patients PSMA was negative in 40% with path N+ disease)

The endpoint of "changes treatment choices" is a horrible endpoint.

The real issue is whether the findings of the test lead to improved outcomes.

The closest we have is the EMPIRE-1 study that used F18-fluciclovine (not PSMA) and found improved biochemical outcomes in the group in whom the PET was used to define salvage therapy.

EMPIRE-1: Randomized Trial Comparing Conventional- vs Conventional plus Fluciclovine (18F) PET/CT Imaging-Guided Post-Prostatectomy Radiotherapy for Prostate Cancer

Molecular imaging is increasingly used to guide prostate cancer decisions and treatment planning. The specific aim was to evaluate the role of fluciclovine ([18] F) PET {positron emission tomography}/CT{computed tomography} [PET] in improving cancer control ...

www.ncbi.nlm.nih.gov

Biochemical outcomes are not great either. EMPIRE-2 will compare F18 Fluciclovine to Ga68 PSMA

PSMA has become ubiquitous. Stage migration has reared its head again.

Ditto squared!

As a semi-WAG by me, I think some nomograms will show a cT3 Gl4+4 PSA 10 guy can have LN probability involvement as low as 15%. If PSMA has a 90% specificity and 75% sensitivity (more educated guesses by me), a positive node by PSMA PET has a ~57% positive predictive value. Calculations like this make me hesitant to base a lot of treatment decisions... to vary from textbook or "standard"... on PSMA PET. I like PPVs of 90+% to change a tx decision, and PSMA PET seldom offers PPVs that high.

In a case where a patient is pN1, the PPV of PSMA PET is admittedly apt to be very high. But you already know he's N+

How insurance companies use PSMA PET to base their decisions on is unscientific as well. So pro-tip... plan and simulate and get prior auth first, get PSMA PET next; or get at least after you've gotten the RT authorizations you want in the best interest of the patient.

 

[Chartreuse Wombat]

Ditto squared!

As a semi-WAG by me, I think some nomograms will show a cT3 Gl4+4 PSA 10 guy can have LN probability involvement as low as 15%. If PSMA has a 90% specificity and 75% sensitivity (more educated guesses by me), a positive node by PSMA PET has a ~57% positive predictive value. Calculations like this make me hesitant to base a lot of treatment decisions... to vary from textbook or "standard"... on PSMA PET. I like PPVs of 90+% to change a tx decision, and PSMA PET seldom offers PPVs that high.

In a case where a patient is pN1, the PPV of PSMA PET is admittedly apt to be very high. But you already know he's N+

How insurance companies use PSMA PET to base their decisions on is unscientific as well. So pro-tip... plan and simulate and get prior auth first, get PSMA PET next; or get at least after you've gotten the RT authorizations you want in the best interest of the patient.

View attachment 383308

Another method is to discuss PSMA findings at a Tumor Board with relevant disciplines. At least once a month I see a single PSMA + (ish) bone lesion; usually ribs. In most cases I will ask that the case be presented and create a note that resides in the chart that the "consensus of the group" is that the finding is a false positive.

https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.15152

 

[BobbyHeenan]

Another method is to discuss PSMA findings at a Tumor Board with relevant disciplines. At least once a month I see a single PSMA + (ish) bone lesion; usually ribs. In most cases I will ask that the case be presented and create a note that resides in the chart that the "consensus of the group" is that the finding is a false positive.

https://bjui-journals.onlinelibrary.wiley.com/doi/10.1111/bju.15152

We do this as well.

Over the years since PSMA came out we've had a small case series of ribs and inguinal nodes that we biopsied. We're like 0/5 on finding cancer in any of these biopsies.

With that said, the amount of peri-rectal nodal failures post-op I see is kind of alarming...not really in my elective CTV volume for standard post op cases.

 

[radiaterMike]

I would call this adjuvant. Just like in the spirit of STAMPEDE we shouldn't use PSMA results to make a call that conventional imaging didn't find, I wouldn't let residual PSMA uptake in the nodes (if CT and MRI are negative or equivocal) after the surgery make this be "salvage." Which you're right is total semantics. I let this paper from D'Amico a few years back take up space in my brain re: the ongoing (ongoing for me, anyways) salvage vs adjuvant debate.

I would treat all obvious PSMA+ lesions (and agree with above that obvious is not always obvious). You can argue that if there are more than a few lesions, and some were not seen on conventional imaging, and that the patient would have qualified for STAMPEDE, he would potentially derive a benefit from SBRT. But I would not leave obvious PSMA+ lesions untreated. I realize insurers do not quite get this. If someone has many metastases, of which only a few are seen on conventional imaging, I would probably backtrack on my stance though. I realize such a patient would have qualified for STAMPEDE but I question whether he really would derive a benefit. Also - what is seen on conventional imaging, and what is seen on conventional imaging in retrospect (after PET) are often not the same. So you are adding subjectivity into this.

 

[ramsesthenice]

We do this as well.

Over the years since PSMA came out we've had a small case series of ribs and inguinal nodes that we biopsied. We're like 0/5 on finding cancer in any of these biopsies.

With that said, the amount of peri-rectal nodal failures post-op I see is kind of alarming...not really in my elective CTV volume for standard post op cases.

Completely agree and the data strongly supports what you see. If the absolute PSA and velocity are not consistent with metastatic disease, be very suspicious of PET detected extra pelvic metastases.

IMO, PSMA PETs have been more useful for the med oncs than me in that it makes it easier for them to give an ARB with ADT for high risk patients who were node negative on conventional imaging. I can only think of a very small number of times that in the intact or salvage setting that they have really impacted what I do beyond boosting gross nodes. Really, it’s the negative scans that have been more helpful. I’m getting lots of referrals for people with in gland recurrences and I’m more inclined to treat them now than I used to be. Of course, you still have to consider everything (doubling time, etc).

For us, where they have been most “helpful” are for the patients with widely metastatic disease who have good responses to systemic therapy and start to develop androgen resistance. They can be very helpful to distinguish between active and treated lesions (particularly in bone) and help decide when focal therapy may be appropriate. Before anyone says anything, no, it is not proven this approach is beneficial though I suspect it does as it does seem to delay castration resistance in a significant subset of the patients I have treated. This is a blessing and a challenge. We really need to study these questions to learn how to manage populations, but we treat patients and when they show up with test results we have to decide what to do with them in the absence of clear data.

 

[TheWallnerus]

All the above ruminations re PSMA PET remind me of Stephen Colbert and gut feelings. I'm guilty too.

"I'm not some member of the 'factanista.' I go from the gut. Did you know you have more nerve endings in your gut than you have in your head? It's true. You can look it up. I know some of you will say 'I did look it up and that's not true.' That's 'cause you looked it up in a book. Next time... look it up in your gut. I did. I speak straight from the gut. That's where the truth lies."

 

[BobbyHeenan]

All the above ruminations re PSMA PET remind me of Stephen Colbert and gut feelings. I'm guilty too.

"I'm not some member of the 'factanista.' I go from the gut. Did you know you have more nerve endings in your gut than you have in your head? It's true. You can look it up. I know some of you will say 'I did look it up and that's not true.' That's 'cause you looked it up in a book. Next time... look it up in your gut. I did. I speak straight from the gut. That's where the truth lies."

Speaking of nerve endings, sacral ganglia uptake is something we see and are careful about. A less experienced reader can call that a bone or node met....

68Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging - PubMed

The study aims to investigate the presence of physiologic prostate-specific membrane antigen (⁶⁸Ga-PSMA)-ligand uptake on PET in cervical, celiac, and sacral ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. <b>Methods:</b> Four...

pubmed.ncbi.nlm.nih.gov

 

[DoctwoB]

Interesting discussion. A few thoughts.

1. Agree this is salvage not adjuvant xrt. Salvage = persistent post op PSA or after BCR. Basing it on path results (node positive, margins, etc) is not salvage.

2. You can safetly wait for continence recovery if PSA controlled on ADT. How long is unclear, but generally I'm in no rush as long as psa undetectable and we are still seeing meaningful improvement in recovery post op.

3. For cN0 pN+ patients with undetectable PSA I will monitor, as 15-30% will have durable disease control. There is plenty of data that treating at lower PSA is better then at higher PSA. I'm unaware of any data that salvage XRT at undetectable psa is better then 0.15

 

[MidwestRadOnc]

Speaking of nerve endings, sacral ganglia uptake is something we see and are careful about. A less experienced reader can call that a bone or node met....

68Ga-PSMA-HBED-CC Uptake in Cervical, Celiac, and Sacral Ganglia as an Important Pitfall in Prostate Cancer PET Imaging - PubMed

The study aims to investigate the presence of physiologic prostate-specific membrane antigen (⁶⁸Ga-PSMA)-ligand uptake on PET in cervical, celiac, and sacral ganglia of the sympathetic trunk as a pitfall for lymph node metastases in prostate cancer imaging. <b>Methods:</b> Four...

pubmed.ncbi.nlm.nih.gov

Very helpful post. Thanks!

 

[evilbooyaa]

I'm seeing someone, Gleason 4+5=9, pre-tx PSA 8. Upfront PSMA showed uptake in a mesorectal and left iliac node. Went for surgery with prostatectomy with lymph node dissection. pT3bN1, margins neg, 1/17 LN. Post-op PSA down to 3 (never undetectable). Post-op PSMA PET showed residual uptake in a single left iliac node, no distant disease. He was started on ADT + zytiga and due to multiple issues (continence, logistical hurdles, etc) I'm only seeing him now 9 months later. PSA is now undetectable.

So I understand that in breast and prostate, we typically have thresholds (which may vary between provider) for when we would consider adjuvant radiation. For breast, I think we often try and start patients within 3 months but may allow up to 6 months. For prostate, if a patient meets indications for adjuvant RT (less so in the radicals/raves era) we start them within 6 months or when continence is recovered to its maximal ability.

My question is - the rationale for not delaying RT too long after surgery is the presumption that residual disease will start to grow and efficacy of RT is diminished. However, if someone is placed on hormone therapy (ADT for prostate or AI for breast), then wouldn't it make sense that regrowth will be inhibited? If so, would it be reasonable to start someone 9 months or 12 months after surgery if they've been on hormone therapy, as the ADT itself is cytostatic, as opposed to RT which is cytotoxic.

I started reading all the other posts following this one and then realized I had missed a lot of discussion.
So, to get back to just the (seemingly more detailed) OP than at initial posting:

Someone with a post-op PSA of 3 that never reaches undetectable, will never be receiving 'adjuvant' therapy. Salvage radiation therapy is indicated at a PSA > 0.2 for those with non-M1 disease. This patient, 100%, has residual disease, and thus any radiation therapy is given in the salvage setting. To me, this is not up for discussion. So for the patient, as described, he needs some form of RT. Whether you treat with SBRT to the gross node alone versus whole pelvis with SIB can be somewhat of a discussion. If we're going for CURE, I favor whole pelvis as per retrospective data (understanding there is no overall survival benefit of doing so), although upcoming PEACE V STORM trial will give us a better sense in a prospective fashion once presented.

Adjuvant RT for prostate cancer is done in the setting of undetectable PSA. Salvage RT is done in the setting of PSA defined as PSA > 0.2. Early salvage is not a time point, but rather a low PSA value (0.1 - 0.2). A patient could be 8 years out from prostatectomy but if PSA is 0.13 and you pull trigger on RT, they are receiving early salvage.

In terms of definition of true adjuvant, as long as patients are 'suppressed' by being on at least ADT post-op, I am OK stretching the time frame. However, similar to many others, I have not done a true case of adjuvant in quite some time given results of RADICALS/RAVES.

So on a related point, what are folks doing for negative PSA but positive pathologic nodes? This is probably the only routine point of contention that I have with our urologists. Its hard for me to imaging that just observing these folks is a good idea regardless of the PSA. In my mind, this should at the very least buy systemic therapy (though I argue for systemic therapy and ADT). I understand the argument that we don't know intervening before the PSA becomes detectable changes the long-term disease course. But unlike prostate only disease, we know in this setting its already second echelon and patterns of recurrence are unclear. Further, we have always considered N+ disease as systemic for prostate cancer, so I am a little unclear why the PSA (which is mostly a measure of disease burden) changes that equation.

There is some limited retrospective data (institutinal, not NCDB, he has two separate papers) from Abdollah that maybe 1 node doesn't need RT and 4+ doesn't benefit from RT (likely due to presence of metastatic disease already) but I would prefer to do adjuvant, or at least get patient started on their 2 years of ADT while awaiting continence recovery.

In these patients, multi-D discussion ends up with these patients generally being observed until their PSA becomes detectable. I guess there was a link that some pN1 patients don't require adjuvant therapy and are 'cured' with surgery alone. But for the rest, we do a PSMA PET/CT and attempt to salvage them. I strongly hesitate to extrapolate RADICALS/RAVES to this situation saying salvage is 'just as good as' adjuvant for all patients with pN1 prostate cancer. That being said, I don't have good data that specifically refutes RADICALS/RAVES, so Urology pushes hard to observe, Med Onc thinks it's reasonable, and we recommend observation until they recur.

I would call this adjuvant. Just like in the spirit of STAMPEDE we shouldn't use PSMA results to make a call that conventional imaging didn't find, I wouldn't let residual PSMA uptake in the nodes (if CT and MRI are negative or equivocal) after the surgery make this be "salvage." Which you're right is total semantics. I let this paper from D'Amico a few years back take up space in my brain re: the ongoing (ongoing for me, anyways) salvage vs adjuvant debate.

The post-op PSA is 3. Forget the PSMA PET for a second. You calling RT delivered when post-op PSA of 3 adjuvant?

Or to exclude patients from curative intent treatment in settings that would have been called curative 10 years ago, but are called M1 and oligo today. E.g., I remember someone asking on Twitter about a year ago what to do with a Gleason 4+4 patient who had a left axillary node on PSMA PET, negative elsewhere, all other imaging negative.

Evaluate whether patient recently received a vaccine shot in their left arm. If yes, ignore the node. If no, biopsy the node. If node biopsy negative, treat definitvely. If positive, treat as per oligometastatic paradigm.

Interesting discussion. A few thoughts.

1. Agree this is salvage not adjuvant xrt. Salvage = persistent post op PSA or after BCR. Basing it on path results (node positive, margins, etc) is not salvage.

2. You can safetly wait for continence recovery if PSA controlled on ADT. How long is unclear, but generally I'm in no rush as long as psa undetectable and we are still seeing meaningful improvement in recovery post op.

3. For cN0 pN+ patients with undetectable PSA I will monitor, as 15-30% will have durable disease control. There is plenty of data that treating at lower PSA is better then at higher PSA. I'm unaware of any data that salvage XRT at undetectable psa is better then 0.15

Excellent post. I agree with everything said here. DoctwoB, as always, appreciate your input on this forum.