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.