Adjuvant RT +/- Adjuvant ADT for a prostate case

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Kroll2013

Kroll2013

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Dear colleagues,
I need your opinion concerning this case:

62 years old patient with no comorbidities, diagnosed of a prostatic adenocarcinoma after rising PSA level on screening.
he underwent a radical prostatectomy with bilateral ilio-obturator dissection:
Pathology showed:
ADK GS 8 (4+4), , 17mm lesion, at the level of the bilateral apex, and extending to the bilateral middle lobes.PNI+, LVSI ?, diffuse high grade PIN,
positive margins at the level of the right apex, posterior middle lobe , both SVs are intact
0/4 LN right dissection, 0/6 left dissection
PSA post-op is 0.07

6 months after the surgery , he is almost completely urinary continent.

what do you suggest as adjuvant treatment?
1- nothing, observe and offer salvage RT if needed
2- adjuvant radiation to prostatic bed
3- adjuvant radiation to pelvis nodes and prostatic bed
4- concomittant adjuvant radiation and short course ADT

ty
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Options 3 and 4.

Positive margins means treat now IMO. This is a case at high risk of recurrence that needs adjuvant RT. The results of the SPPORT trial would push me to treat pelvis and add ADT. Would others also add some docetaxel to the mix?
 
I think this is salvage (not adjuvant) RT given that the PSA is detectable. I favor STADT + XRT. I am not persuaded to treat the pelvis as the benefit in SPPORT was only biochemical and only observed in the group with PSA above 0.34 (if memory serves). I will not treat the nodes until there is a difference observed in clinically meaningful outcomes like DM or PCSM. Remember RTOG 9413 was originally "positive" based on PSA criteria but no differences in DM, PCSM were observed.
 
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Chartreuse Wombat said:
I think this is salvage (not adjuvant) RT given that the PSA is detectable.
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Maybe it's semantics but I thought salvage meant: PSA had gone to 0 postop, then became detectable again. I.e., it's a recurrence that you're salvaging. This pt doesn't have recurrent disease, he has persistent disease.

Just to confirm, the positive margin was positive for tumor (not just retained prostate tissue)? If positive margin was positive for tumor, was the positive margin: (a) tumor inside the prostate (i.e., surgeon cut into the prostate), or (b) tumor outside the prostate (extra-prostatic extension)? Also, by "both SVs intact" you mean they were removed and uninvolved with tumor? Because if the surgeon left behind normal prostate and/or SVs, that could be contributing to detectable PSA.

Assuming the positive margin is positive for tumor, I would consider RT (~66 Gy) to the fossa + short-term ADT (given detectable PSA). Be generous and/or consider boosting the areas of known positive margin.
 
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Neuronix said:
Options 3 and 4.

Positive margins means treat now IMO. This is a case at high risk of recurrence that needs adjuvant RT. The results of the SPPORT trial would push me to treat pelvis and add ADT. Would others also add some docetaxel to the mix?
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No data in post op setting AFAIK.

I've noticed med oncs in my neck of the woods have gotten away from pushing adjuvant taxotere at all in high risk patients getting definitive xrt with long term adt... One of them mentioned some study in Europe that didn't confirm was what was found in rtog 0521
 
medgator said:
No data in post op setting AFAIK.
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I am extrapolating here, I admit. I could be talked out of it, but I've been veering towards more and more for these patients based on the recent trial data.

Then again it's interesting whether this is truly adjuvant or salvage at this point. I agree with the arguments that this is practically a salvage case.
 
I think we should distinguish a few scenarios:
  1. Persistently detectable post-op PSA due to residual normal prostate or SVs. In this scenario, margins would be negative for tumor and PSA would not rise on serial monitoring. Need to ensure pt is not in this group before treating.
  2. High-risk postop but undetectable PSA: T3 or positive margins. A standard adjuvant scenario for RT alone.
  3. Persistently detectable post-op PSA due to residual tumor. Whether we call this adjuvant or salvage, it is like salvage in that there is enough residual tumor to be biochemically detectable and I think it should be treated the same.
  4. PSA recurrence after initial undetectable postop PSA. A standard salvage scenario for higher dose RT and ADT.
 
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I'd treat the fossa + ADT. I haven't been impressed with any data looking at nodal coverage, either in the definitive or salvage setting. Duration of ADT tough to know based on the data we have right now.
 
I'd treat fossa due to + margin
What's the level of evidence for hormones in this scenario?
 
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Re: nodes. Anybody know how many pts on 0534 had PLND? It was permitted but I don't know how many got it. Question is what is the marginal value of RT to pelvic nodes in the face of 0/10 LN involved on PLND. Also relevant I think is the fact that this is persistent disease immediately post-prostatectomy with a positive prostate margin (hence the persistent disease is likely in the fossa), vs subsequent recurrence (where perhaps the nodal risk is higher than in this case).

Building off of the other thread, would anyone get fluciclovine or (if available) PSMA PET in the hope of localizing residual disease?

seper said:
What's the level of evidence for hormones in this scenario?
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Quite strong -- RTOG 9601. This pt appears to fit 9601 enrollment criteria: T3 or positive margins, PSA 0.2-4.0 at least 8 wks postop.
 
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I think this case can be spun in a number of different ways. A persistent PSA of any value in the presence of a positive margin and high gleason score should be thought of as persistent disease. At large centers in this setting, I do see a lot of pts treated with pelvic/ln xrt and at least 6 months of hormones. In terms of lymph node dissection in prostate cancer, it is somewhat of a sham procedure and I would not take that into account.
 
Radiator20 said:
Re: nodes. Anybody know how many pts on 0534 had PLND? It was permitted but I don't know how many got it. Question is what is the marginal value of RT to pelvic nodes in the face of 0/10 LN involved on PLND. Also relevant I think is the fact that this is persistent disease immediately post-prostatectomy with a positive prostate margin (hence the persistent disease is likely in the fossa), vs subsequent recurrence (where perhaps the nodal risk is higher than in this case).

Building off of the other thread, would anyone get fluciclovine or (if available) PSMA PET in the hope of localizing residual disease?


Quite strong -- RTOG 9601. This pt appears to fit 9601 enrollment criteria: T3 or positive margins, PSA 0.2-4.0 at least 8 wks postop.
Click to expand...

upload_2019-2-22_10-34-19.png


64.4% got PLND



As to the rest of the case - lots of good points above, but this is truly in a gray zone area, primarily due to how much PSA testing sensitivity has changed in the past decade or so.

Failure after prostatectomy was historically defined as > 0.2, usually due to sensitivity of PSA testing. That sensitivity improved to identifying anybody with PSA > 0.1. Now ultra-sensitive PSA exists that can identify anybody > 0.04. While I think we all look for reasons to treat, I personally wonder if PSA > 0.2, PSA > 0.1, and PSA > 0.04 all require the same amount of treatment, as that's the extrapolations we are all making. PSA of 0.07, while positive now, would have been negative anytime > 3-5 years ago.

First branchpoint- if you're calling the PSA detectable, then this is salvage. Salvage means either for recurrent disease (post-op PSA to 0, then to 0.2) or persistent disease (post-op PSA never to 0). If the PSA is detectable then you should treat with RT now. Whether to use hormones honestly depends on your personal feelings (is BRFS sufficient to add hormones, or does there need to be a PCSM or OS benefit) on the matter. If you're minimizing BRFS only, then GETUG tells us to give this patient hormones regardless of his PSA. If you believe only in PCSM/OS, then RTOG 9601 subset says no need for hormones in this patient, b/c no survival benefit with PSA < 0.7. Deciding whether to cover the nodes again depends on whether you believe in BRFS or require clinical endpoint differences. It showed that giving ADT to PBRT still improves BRFS even with PSA < 0.34. If you are giving ADT, there is no benefit on patients with PSA < 0.34 of covering nodes. 0534 did not have a PBRT + nodes arm without ADT. If you want to do RT to fossa and nodes without ADT, you are in a data-free zone.

If you're calling this PSA undetectable (as it would have been as recently as 3-5 years ago, and even now at community places that don't have ultrasensitive PSA testing) then you can consider adjuvant RT vs wait for early salvage (when PSA crosses 0.1). Adjuvant RT has no data to recommend use of hormones. Given that he's continent and has a positive margin, I would consider treating with aRT based on the trials.

What would my recommendation be for this patient? I'd call the PSA detectable, call it salvage, and radiate the fossa alone. I'd offer him 6 months of ADT but wouldn't be a huge stickler about it. I would not radiate nodes with a PSA of 0.07.

TL;DR - If you're calling the PSA detectable, then this is salvage, and options 2-4 are reasonable. If you're calling the PSA undetectable, then options 1-3 are reasonable.
 
Sorry to be a stickler but he would not be eligible for 9601 given his PSA <0.1. ANother trial arguing for ADT in this setting is the GETUG trial but that required a PSA of at least 0.1 as well. Technically he would not be eligible for either study. Having said that I would recommend STADT.
 
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Psa persistence could be benign disease or residual cancer. Obviously more concerning for cancer in setting of positive margin, but still not unreasonable to watch and wait and treat as salvage if his PSA rises to .2. Remember, positive margin is a relatively weak predictor for BCR (though we’re talking about persistence, not Recurrence)

I’d leave it up to patient. I’d tell him best oncologic outcomes are likely for up front xrt with short course ADT, with the caveat that we’re over treating a certain percentage of patients. Following PSA and early salvage at .2 is also reasonable, but may (or may not, no good data to guide) be trading off some oncologic efficacy for a smallish chance to avoid future treatment.
 
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DoctwoB said:
Psa persistence could be benign disease or residual cancer. Obviously more concerning for cancer in setting of positive margin, but still not unreasonable to watch and wait and treat as salvage if his PSA rises to .2. Remember, positive margin is a relatively weak predictor for BCR (though we’re talking about persistence, not Recurrence)

I’d leave it up to patient. I’d tell him best oncologic outcomes are likely for up front xrt with short course ADT, with the caveat that we’re over treating a certain percentage of patients. Following PSA and early salvage at .2 is also reasonable, but may (or may not, no good data to guide) be trading off some oncologic efficacy for a smallish chance to avoid future treatment.
Click to expand...

Only part I disagree with is that there's data that salvage earlier than 0.2 is better than waiting until 0.2. Historically it was 0.2 because that's how sensitive PSA detection was. I think delaying until PSA crossed 0.1 would not be unreasonable.
 
Just my thoughts...

PSA 0.07 is very low, close to the undetectable level. I would not see that value as a sign of residual, active disease. I would remeasure, before calling it residual disease.
I do not see an indication for ADT, if one was to irradiate in the adjuvant setting or early-salvage, if you still consider a PSA of 0.07 as residual disease. There is no randomized data showing that ADT is of benefit in purely adjuvant RT or salvage RT at very low PSA levels.

Apart from all that...

I would talk with the patient and offer both options:

Irradiation of the prostate fossa now as adjuvant treatment vs. monitoring and treatment when PSA rises.

Both options are valid and from my experience many patients rather wait.


RTOG 0534 did not show an overall survival benefit with short term ADT, it was merely PFS.
But that's a no brainer. In my experience 15-20% of the patients presenting for salvage RT in the context of rising PSA never respond to RT and the PSA just keeps rising throughout treatment and on follow up. All these patients benefit in terms of PFS by the addition of ADT.
If and when RTOG 0534 or any other trial will actually show that ADT provides an OS-benefit at low PSA-values (unlike RTOG 9601 which only showed it at high PSA-values), would I consider it standard of care.
 
Pointless said:
No seriously... what? This is /sarcasm hopefully?
Click to expand...
Guy giving Astro lecture from univ if Chicago was a penile clamp enthusiast. Personally never used one. Probably wouldn’t last long in my clinic. Number of staff members would end up taking it home.
 
Have any of you observed an association of PSA recurrence or more rapid PSA doubling time in the setting of receptor agonist medications?

I have a rather low risk postop prostate with rapidly rising PSA since starting a glucagon receptor agonist for type 2 diabetes.
 
Pointless said:
Ah the ol' citing an abstract with 8 patients to prove a point move.... OK, sure, I should have clarified that in the setting of total incontinence, you can clamp to your heart's delight. I just found the out-of-left-field suggestion to clamp this completely continent gentleman to be a little humorous... and terrifying.
Click to expand...

Please read the thread before jumping to criticism. Haybrant already said he misread.
Haybrant said:
Oops read that wrong.
Click to expand...
 
Palex80 said:
I wouldn't irradiate totally incontinent patients with the purpose of delivering ADJUVANT treatment. Salvage is another story...
Click to expand...
Yeah I was thinking more in the salvage setting, specifically.

Basically any situation where I don't want the pt urinating on the table because they are trying to keep a full bladder through treatment
 
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medgator said:
Yeah I was thinking more in the salvage setting, specifically.

Basically any situation where I don't want the pt urinating on the table because they are trying to keep a full bladder through treatment
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Bingo.

Nothing worse than urine getting into the head of the machine on a PA field, laying the next patient down, and then swinging it to the AP field.

EDIT: Gave it some thought. There are worse bodily substances that could happen with, but I won't go there.
 
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evilbooyaa said:
Only part I disagree with is that there's data that salvage earlier than 0.2 is better than waiting until 0.2. Historically it was 0.2 because that's how sensitive PSA detection was. I think delaying until PSA crossed 0.1 would not be unreasonable.
Click to expand...

Agree, but in practice I tend to use 0.2 just because PSA assays can be fickle and vary with time and between labs. If I have a patient going 0.02 -> 0.06 -> 0.1 in a short time period I'll absolutely point towards salvage, but often it ends up being 0.03 -> 0.12 -> 0.04 -> undetectable -> etc. I've never had a good answer for this, and in fact our literature tells us that basically every studied factor (DRE, bike riding, diet, etc) beyond acute prostatitis or immediately post biopsy shouldn't affect your PSA, but in practice it seems to fluctuate a lot more then it should.

Hell we even had a local Quest that was rounding undetectable PSAs to 0.1. That was fortunately caught early but caused quite the uproar.
 
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DoctwoB said:
If I have a patient going 0.02 -> 0.06 -> 0.1 in a short time period I'll absolutely point towards salvage, but often it ends up being 0.03 -> 0.12 -> 0.04 -> undetectable -> etc. I've never had a good answer for this, and in fact our literature tells us that basically every studied factor (DRE, bike riding, diet, etc) beyond acute prostatitis or immediately post biopsy shouldn't effect your PSA, but in practice it seems to fluctuate a lot more then it should.

Hell we even had a local Quest that was rounding undetectable PSAs to 0.1.
Click to expand...
Different labs use different assays. There are not entirely human-error-free ways of "prepping" the PSA specimens. Re: the equipment used to detect, with a very tiny signal (ie a small PSA), the SNR will obviously be lower (especially with just one significant digit in the PSA number) leading to variable readings from the same sample, from the same lab, from the same technician, and so forth. The clinical lab is a bit of a black box; don't get me started on how they choose "normal" values reported in the labs. But any time you measure something, no matter how great your measuring tool, you will always get different values on the same measured specimen. You can measure such things as the half-life of a neutron and get significantly different results every time. We can't agree on what a kilogram is so it's unlikely we can agree on how much PSA one one-hundredth of a nanogram per milliliter PSA is. In p-chem in college, we had to report SEMs or error bars with all our measurements; for doctors looking at human serum chemistry results, they're not as picky as chemists and error bars are never reported. For PSA results 0.03 -> 0.12 -> 0.04 -> undetectable... 1) the error bars likely overlap (100% likely overlap at a certain confidence level), and 2) there is ~100% likely not actually zero molecules of PSA in the patient's blood in the last readout. Rounding all those values, including the "undetectable," to 0.1 is not bad science. But it makes folks uncomfortable! Kind of reminds me of this story I heard one time that Tide sold WAY more laundry detergent powder when they put the blue crystals in the white powder. The blue crystals did nothing, but it made people think the detergent was better. Reporting a PSA of 0.01 vs 0.1 may make people (doctors and patients) feel better, but it's likely (or at best possibly) mathematical blue crystals.
 
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Mandelin Rain said:
Nothing worse than urine getting into the head of the machine on a PA field, laying the next patient down, and then swinging it to the AP field.
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That feels like a particularly unpleasant service visit for the linac tech...

Palex80 said:
I wouldn't irradiate totally incontinent patients with the purpose of delivering ADJUVANT treatment. Salvage is another story...
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In someone with indications for adjuvant RT, but post-op incontinence and/or ED, how long if at all are folks waiting for sx to improve before pulling the trigger on adjuvant RT?
 
Radiator20 said:
In someone with indications for adjuvant RT, but post-op incontinence and/or ED, how long if at all are folks waiting for sx to improve before pulling the trigger on adjuvant RT?
Click to expand...

Generally 6 months max, IMO. After that point we can just wait until patient develops recurrence. More for incontinence, if isolated ED I don't think waiting for RT is going to help them. Also, I would only wait for incontinence if they were actually improving between month 3 and 6.
 
Yeah, 4-6 mo is what I was taught as well. I guess the things that are less satisfying to me:

1) Urinary QOL continues to improve markedly between 6 mo and 12 mo per PROTECT. (Whereas ED recovery is much slower and less complete.) So, one might gain further urinary recovery by waiting >4-6 mo.

2) Prompt adjuvant -> delayed adjuvant -> early salvage is really just a continuum of waiting for undetectable disease to grow into detectable disease. (Although, of course, this will not happen for all patients.) But, point is, given that salvage RT is effective, adjuvant RT delayed beyond 4-6 months is very likely also quite effective. So, one might not lose that much oncologic effectiveness by waiting >4-6 mo. (This is, of course, in distinction to a lot of other disease sites where RT is not an effective local salvage modality and so really must be given as prompt adjuvant therapy if it's going to be given.)

Not necessarily advocating for delay >4-6 mo, just thinking out loud.
 
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I mean until RAVES and RADICALS come out, if they're extending beyond 6 months just wait until they're at salvage. I agree not really evidence-based, but you have to have a line at some point right? Can't have somebody at 1.5 years out that you're treating 'adjuvantly'.
 
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