FLAME TRIAL prostate boost - ?lymph nodes?

[BobbyHeenan]

I know on the FLAME trial they did not cover lymph nodes electively.

I have had good outcomes with mostly unfav int risk patients that I've treated per the flame regimen (35 fractions). I've tried to keep my treatment as close to protocol parameters as possible. I really like it for patients that fit enrollment criteria and there is a well definted boost target with congruent biopsy findings.

I have a guy now that is a great candidate for this - very well delineated MRI target, congruent location on biopsy, even his PSMA is focally hot here and no where else in prostate. He has G9 disease but no lymph node mets on PSMA. PSA single digits.

I often cover lymph nodes for high risk non FLAME cases. Usually I do 70 Gy prostate and 50.4 nodes here in 28 fractions. POP-RT says maybe this is helpful.

I have contemplated something like 1.6 Gy (56 Gy) to nodes, 77 Gy to Prostate PTV, then the intraprostatic boost....but it doesn't set right with me.

I have been doing some FLAME-like cases at 70/28 to prostate and then like 80ish to the boost. I guess I could treat nodes 50.4 Gy in that situation.

Any thoughts here? I think I may just stick to no elective XRT here...with a VERY hot PSMA scan in the prostate focal lesion (SUV > 40) I feel like maybe no nodes are truly involved now.

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[A_DeMichele]

there is no good evidence to treat pelvic nodes in prostate cancer, I almost never do. you’re OK

 

[Music Man Stan]

there is no good evidence to treat pelvic nodes in prostate cancer, I almost never do. you’re OK

BobbyHeenan mentioned the POPRT trial above but in case you haven't read it, here's the link: https://ascopubs.org/doi/10.1200/JCO.20.03282?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed

Also in post-prostatectomy cases, RTOG 0534 also supports lymph node treatment. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01790-6/fulltext



To answer the original post, I personally follow the dosing recommendations in the current NRG GU009 and GU010 protocols which try to achieve the same BED as FLAME. I typically talk to all patients about 5, 28, or 40 treatment regimens.

For SBRT, 25Gy to elective nodes, 45Gy to the MRI delineated gross disease, 40Gy to the prostate, 36.25Gy to the proximalSV assuming that there's no gross involvement. Big disclaimer is that I've always chickened out doing 5Gy x 5 to such a big field so I never do elective nodal with SBRT.

For 28 treatment regimens, I'm doing 50.4Gy to nodes, 70Gy to prostate/proximal SV, and 88.2Gy to the MRI delineated gross disease.

For 40 treatment regimens I'm doing 50Gy in 25 treatments to prostate/proximal SV + nodes with simultaneous boost at 2.47Gy/fx boost to the MRI delineate nodule. Then cone down 30Gy in 15 treatments to prostate/proximal SV with continued simultaneous boost at 2.47Gy/fx for a total of 98.8Gy.

 

[dieABRdie]

BobbyHeenan mentioned the POPRT trial above but in case you haven't read it, here's the link: https://ascopubs.org/doi/10.1200/JCO.20.03282?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub 0pubmed

Also in post-prostatectomy cases, RTOG 0534 also supports lymph node treatment. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01790-6/fulltext



To answer the original post, I personally follow the dosing recommendations in the current NRG GU009 and GU010 protocols which try to achieve the same BED as FLAME. I typically talk to all patients about 5, 28, or 40 treatment regimens.

For SBRT, 25Gy to elective nodes, 45Gy to the MRI delineated gross disease, 40Gy to the prostate, 36.25Gy to the proximalSV assuming that there's no gross involvement. Big disclaimer is that I've always chickened out doing 5Gy x 5 to such a big field so I never do elective nodal with SBRT.

For 28 treatment regimens, I'm doing 50.4Gy to nodes, 70Gy to prostate/proximal SV, and 88.2Gy to the MRI delineated gross disease.

For 40 treatment regimens I'm doing 50Gy in 25 treatments to prostate/proximal SV + nodes with simultaneous boost at 2.47Gy/fx boost to the MRI delineate nodule. Then cone down 30Gy in 15 treatments to prostate/proximal SV with continued simultaneous boost at 2.47Gy/fx for a total of 98.8Gy.

We have been doing pelvic nodes to 50.4 in 28 fractions with conventional fractionation then cone down to prostate when doing an MRI guided SIB like FLAME. Glad to hear some other people are doing it. I was kind of nervous to adopt something not many others are doing; but there aren't many prostate regimens that show improved biochemical control without increased toxicity. I hadn't had the guts to boost with a hypofractionated regimen, or to treat elective nodes with SBRT till we have more data in that regard.

 

[Palex80]

I would treat the pelvis, just like you said. Evidence from POP-RT is good in my opinion, and the trial has the great advantage of actually including patients with high risk tumors and a relevant risk of subclinical node positive prostate cancer, unlike the past trials (RTOG 9413 + GETUG 01) which actually included a lot of patients with intermediate risk tumors.

There are several possible avenues for fractionation.

We generally hypofractionate high-risk tumors too with 20Fx and have been doing 20 x 2.2 Gy to the pelvis, 20 x 3 Gy to the prostate.
One can add a focal boost to the prostate as per DELINEATE (67 Gy in 20 fractions).

 

[Radonky]

POP-RT had PSMA PET in a large portion of their patients to screen out macroscopic disease and like others have mentioned, it is good evidence to use to treat the nodes. DMFS was improved (caveat, exploratory, since it was not known to be associated with OS at time of trial inception) in these patients as well.

 

[SneakyBooger]

No elective LN XRT.

 

[BobbyHeenan]

Ha - appreciate the responses. Good to know there are lots of varying relevant opinions.

 

[evilbooyaa]

If I'm doing 28Fx I do similar to you.

If I'm doing conventional, I treat everything at 1.8-2Gy except the FLAME area which goes at about 2.3Gy x 44Fx for my preference. Equal EQD2 to what FLAME used.

I consider the benefit of FLAME boost to be escalating EQD2 to MRI defined lesion, not to their exact dose/fractionation scheme.

Whether I am doing a FLAME boost or not is completely unrelated to whether a patient meeds indications for elective nodal RT. GS 9 with a negative PSMA PET, I would review MSKCC nomogram and then recommend ENI as per POP-RT.

 

[TheWallnerus]

I treat everything at 1.8-2Gy except the FLAME area which goes at about 2.3Gy x 44Fx for my preference.

I have to chuckle a little bit, not at you at all, but at rad onc in general ‘cause first off, this is not what was done in FLAME. FLAME was more FLAME-y. And second, so many radonc are all “LQ sucks” and “don’t fall for alpha beta lies” (especially for SBRT eg, which can like be 5 or 6 Gy fractions)… but same rad oncs are like “well I came up with a good alternative recipe for my own thang that follows LQ” when convenient. Intelligent neuroticism maybe.

 

[Palex80]

I have to chuckle a little bit, not at you at all, but at rad onc in general ‘cause first off, this is not what was done in FLAME. FLAME was more FLAME-y. And second, so many radonc are all “LQ sucks” and “don’t fall for alpha beta lies” (especially for SBRT eg, which can like be 5 or 6 Gy fractions)… but same rad oncs are like “well I came up with a good alternative recipe for my own thang that follows LQ” when convenient. Intelligent neuroticism maybe.

Principally, you are correct. Dose escalation of the dominant nodule in prostate cancer seems to offer a better bPFS. Is there a clear dose that should be delivered to achieve optimal results both in terms of target coverage and in terms of organs at risk? We do not know.
Just get in as much dose as you can, safely, appears to be the message of the trial. I do however understand if some people will choose to give less dose or are concerned about stuff like the urethra, which we normally do not pay attention to in standard/moderate hypofractionated treatments.

 

[evilbooyaa]

I have to chuckle a little bit, not at you at all, but at rad onc in general ‘cause first off, this is not what was done in FLAME. FLAME was more FLAME-y. And second, so many radonc are all “LQ sucks” and “don’t fall for alpha beta lies” (especially for SBRT eg, which can like be 5 or 6 Gy fractions)… but same rad oncs are like “well I came up with a good alternative recipe for my own thang that follows LQ” when convenient. Intelligent neuroticism maybe.

I am not a LQ or BED/EQD2 poo-pooer. Those who poo-poo are encouraged to provide an alternative model. I'm sure it's not perfect. But not all things need to be perfect. It's the best estimation until we have actual clinical data on dosimetric predictors of toxicity.

I do not hold onto the antiquated belief that the a/b of prostate cancer is 3 or less, however

 

[TheWallnerus]

Principally, you are correct. Dose escalation of the dominant nodule in prostate cancer seems to offer a better bPFS. Is there a clear dose that should be delivered to achieve optimal results both in terms of target coverage and in terms of organs at risk? We do not know.
Just get in as much dose as you can, safely, appears to be the message of the trial. I do however understand if some people will choose to give less dose or are concerned about stuff like the urethra, which we normally do not pay attention to in standard/moderate hypofractionated treatments.

That’s just always seemed hubris to me to decide what a trial’s “message” is. (Do experiments give messages?) If the message of the trial is maximum safe dose escalation, then the FLAME trial texts/emails that seed brachytherapy should be *chef’s kiss*. YMMV. (Your message may vary.)

 

[sirspamalot]

Maybe breast is the wurst.. But the prostate ain't too far behind the hotdog...

 

[grenz]

If you look at the model in the primary FLAME paper (biochemical progression vs GTV dose), you start seeing diminishing returns after about 88 Gy. I’ve been doing 1.8 to the whole gland and 2Gy simultaneous to the DIL.

 

[BobbyHeenan]

again, like so much I find it hard to be dogmatic so lots of good approaches.

How flame is unique in this space is that it achieved better outcomes without more toxicity….which can’t be said about ASCENDE or the older dose escalation trials.

Obviously I can’t know for sure if it was the technique (using vmat/igrt to focally boost worst disease) or if there is something more “foregiving” about the longer 35 fraction course versus a focal boost at higher dose/fraction. I suspect the hypoflame trial will show similar outcomes but because of the unique outcomes for flame I try to stay true to the trial fractionation for the most part.

Good to get lots of perspectives. I wasn’t sure how strict to exact fractionation scheme people were.

 

[Palex80]

How flame is unique in this space is that it achieved better outcomes without more toxicity….which can’t be said about ASCENDE or the older dose escalation trials.

The dose contraints of the FLAME trial are not so easy to find. They are in the supplementary Word file of the toxicity paper.

Standard whole prostate gland radiotherapy with and without lesion boost in prostate cancer: Toxicity in the FLAME randomized controlled trial - PubMed

In intermediate- and high-risk prostate cancer patients, focal dose escalation integrated with standard EBRT did not result in an increase in GU and GI toxicity when compared to the standard treatment up to two years after treatment. This suggests that the described focal dose escalation...

pubmed.ncbi.nlm.nih.gov

The dose constraints were the same in both arms. This trial performed isotoxic dose escalation, which is likely the key difference to other trials.
Interestingly, no dose constraints for the urethra.

 

[sirspamalot]

FLAME me if you must, but I don't see it as being the new community standard in the immediate future.

 

[dieABRdie]

The dose constraints were the same in both arms. This trial performed isotoxic dose escalation, which is likely the key difference to other trials.
Interestingly, no dose constraints for the urethra.

I've definitely started using a urethral dose constraint per:

Urethral and bladder dose-effect relations for late genitourinary toxicity following external beam radiotherapy for prostate cancer in the FLAME trial - PubMed

Further increasing the dose to the bladder and urethra will result in a significant increase in GU toxicity following EBRT. Focal boost treatment plans should incorporate a urethral dose-constraint. Further treatment optimization to increase the focal boost dose without increasing the dose to...

pubmed.ncbi.nlm.nih.gov

I have no interest in the below.....

"Grade 4 GU toxicity occurred in one patient, who required a permanent urinary diversion due to severe incontinence, three years after treatment. Urethral strictures occurred in 18 patients (4%), requiring medical interventions including urethral dilatation, urethrotomy or daily intermittent self-catheterization. Over half of the strictures (13/18) occurred more than two years after treatment. In one patient a cystectomy including a partial prostatectomy was required four years after radiotherapy, because of urethral necrosis following a urethrotomy earlier that year. We did not determine the location of the urethral strictures."

 

[evilbooyaa]

I have a (IMO) relatively conservative urethra constraint when doing FLAME boosting. Boils down to point dose less than 105-107% of whatever Rx the whole prostate is getting.

 

[BobbyHeenan]

I have a (IMO) relatively conservative urethra constraint when doing FLAME boosting. Boils down to point dose less than 105-107% of whatever Rx the whole prostate is getting.

I do similar. I contour a generous urethra PRV and keep it below 110% of 77 Gy.

 

[SneakyBooger]

I thought this was the thread with the reference showing 91% of rad oncs' completely miss a lesion on multi parametric MRI? To be fair, the reference lesion was drawn by "experts" with 7 or less years of experience, so I guess we are also broadening the definition of "expert" nowadays.

Here's the reference for unacceptable contouring on MRI:

"In the study, 40 of 44 participants (91%) completely missed ≥1 target"

No FLAME for me.

POP-RT? Not a believer here either. Although in this current era of poorly done trials it might be better than many. Or maybe it is just our quick acceptance of the results from post hoc analyses and poorly done non inferiority studies. Once we see a single institution study with low patient numbers, a 30% exclusion rate without any explanation, 20% of pts had permanent ADT (orchiectomy), an unplanned/post hoc/exploratory/secondary analysis/"surrogate" DMFS benefit, high long term attrition rate - despite all that, like Pavlov's dogs our specialty immediately begins salivating and takes the treat. Never mind that it is another of a multitude of trials showing no overall survival benefit. Only 27 pts in POP-RT developed DMs. Only 24 died. "Late bowel and bladder toxicities were updated at median follow-up of 68 months (Table 2). Cumulative >/= grade II late GU toxicity was significantly higher with WPRT (20.0% v 8.9%, P 5 .02), while no statistically significant difference was observed for >/= grade II late GI toxicity (8.2% v 4.5%, P 5 .28)." My conclusion, the data shows the vast majority of these men die of something other than prostate cancer so why would I want to double the toxicity risk while not making them live any longer.

I will wait for the results of RTOG 0924 which is powered for an OS analysis. Who wants to wager on the results?

Next, lets talk about ADT for intermediate risk prostate ca and how a post hoc analysis was used to change the NCCN guidelines...

 

[BobbyHeenan]

I thought this was the thread with the reference showing 91% of rad oncs' completely miss a lesion on multi parametric MRI? To be fair, the reference lesion was drawn by "experts" with 7 or less years of experience, so I guess we are also broadening the definition of "expert" nowadays.

Here's the reference for unacceptable contouring on MRI:

"In the study, 40 of 44 participants (91%) completely missed ≥1 target"

No FLAME for me.

POP-RT? Not a believer here either. Although in this current era of poorly done trials it might be better than many. Or maybe it is just our quick acceptance of the results from post hoc analyses and poorly done non inferiority studies. Once we see a single institution study with low patient numbers, a 30% exclusion rate without any explanation, 20% of pts had permanent ADT (orchiectomy), an unplanned/post hoc/exploratory/secondary analysis/"surrogate" DMFS benefit, high long term attrition rate - despite all that, like Pavlov's dogs our specialty immediately begins salivating and takes the treat. Never mind that it is another of a multitude of trials showing no overall survival benefit. Only 27 pts in POP-RT developed DMs. Only 24 died. "Late bowel and bladder toxicities were updated at median follow-up of 68 months (Table 2). Cumulative >/= grade II late GU toxicity was significantly higher with WPRT (20.0% v 8.9%, P 5 .02), while no statistically significant difference was observed for >/= grade II late GI toxicity (8.2% v 4.5%, P 5 .28)." My conclusion, the data shows the vast majority of these men die of something other than prostate cancer so why would I want to double the toxicity risk while not making them live any longer.

I will wait for the results of RTOG 0924 which is powered for an OS analysis. Who wants to wager on the results?

Next, lets talk about ADT for intermediate risk prostate ca and how a post hoc analysis was used to change the NCCN guidelines...

These are good points.

I am selective about when I rec'd FLAME. I have an excellent fellowship trained MRI prostate radiologist that is very good about labeling individual index lesions on multiple series, grading them out, etc. Without doxxing myself I also have publications in this space (MRI prostate boosting). I have been limiting the FLAME patients to those where I feel confident about the MRI lesion and it is also congruent with biopsy findings/location. If there is a PIRAD5 lesion for instance at R base but the biopsies are all negative there and a G4+3=7 is at left apex, I'm not doing FLAME on that patient.

Not sure if that's the right thing to do but it's how I'm thinking about things right now.

I definitely think having an experienced MRI prostate radiologist is incredibly helpful (?necessary?). Same goes for reading rectal MRI's and post-spaceOAR MRI's.

 

[evilbooyaa]

Agree that biopsy location has to be concordant with MRI for me to entertain a FLAME boost.

Having a well-read MRI or a body radiologist you can go through it with would be very valuable as well.

 

[SneakyBooger]

Also, MDACC has shown that men will trade a shorter survival time in order to avoid the side effects of ADT. I expect they would choose the same to avoid the side effects of (pelvic) radiotherapy if it were to provide an OS advantage.

MDACC, 2022: Patients’ Preferences for Androgen Deprivation Therapy in the Treatment of Intermediate-Risk Prostate Cancer

“An incremental benefit of adding short-term ADT to dose-escalated radiation therapy has been suggested in randomized trials but has not been definitively established in practice.”

"willing to trade 3.0 mo of life expectancy to avoid fatigue, 1.8 mo to avoid sexual side effects due to ADT, and 0.6 mo to avoid hot flashes."

"patients who received and declined ADT were willing to accept treatment in anticipation of 10-y OS benefits of 8% and 16%, respectively, which exceed the estimates of the OS benefit of ADT reported in recent secondary analyses of large trials."

"A recent secondary analysis of the Prostate Cancer Study (PCS) III showed that patients with unfavorable intermediate-risk disease had no difference in OS with the addition of short-term ADT (10-y rate 75% v. 74%; P = 0.60)."

"a secondary analysis of the EORTC 22991 demonstrated that patients with unfavorable intermediate-risk disease treated with short-term ADT had no difference in 10-y OS (80% v. 74.3%; P = 0.082)." (NOTE: JCO Commentary stated this is the most robust data for ADT in IR Px Ca currently)

"The ongoing RTOG 08-15 trial reported interim results demonstrating no OS benefit with the addition of short-term ADT to dose-escalated RT (5-y OS 91% v. 90%; P = 0.22)."

"The estimated nominal 10-y OS benefit from these trials was 1.0% in PCS III and 5.7% in EORTC 22991, both of which fall short of the 10-y OS benefits of 8% and 16% needed to be indifferent to taking ADT determined in the current study."

OUCH - Bias...

 

[evilbooyaa]

I believe there is value of improving bPFS if we can do it without ADT, which is essentially what POP-RT showed. Most of my patients who get nodal RT have a negative PSMA PET which is in-line with their methodology.

I think there is room for variation in practice here, but I'd feel kinda stupid if say a VHR patient recurred in the nodes when I treated prostate alone. I would be open to it for a well-read patient strongly motivated to avoid toxicities of PLNRT (which I agree that it definitely is, and anyone who claims otherwise is most likely obfuscating data in some manner).

 

[SneakyBooger]

do it without ADT, which is essentially what POP-RT showed.

Booya, not sure I follow. All pts in POP-RT got ADT, with 20% getting permanent ADT (orchiectomy).

Sneaky thoughts:

I'm not sure the POP-RT results are what I see in my practice. There are too many "Regional with Distant Mets" after PORT compared to what I see.

My gut tells me the vast majority of biochem recurrences that I see are pelvic LN recurrences. Perhaps they followed pts differently than I do. Perhaps I am getting PET's sooner than POP-RT given their high rate of distant mets in pts initially staged as M0 with preRT PSMA. Perhaps their PET scanner is of lower quality. I don't know.

Once a pt has LN recurrence, I treat those patients with salvage pelvic XRT (notice I didn't say WPRT, another discussion for another day). I might salvage some, but more likely it delays progression in many to help keep them off ADT for longer.

Now I have avoided over radiating those who weren't going to benefit from WPRT in the first place and thereby halved that group's risk of RT toxicity and there is no known detriment to their overall survival probability.

I see a patient developed neuroendocrine dedifferentiation in the WPRT group - did WPRT influence that. What about higher 2nd malignancy risk in WPRT in a group of men where the majority are going to live over 10Y? Lots to digest.

 

[SneakyBooger]

However, they should have used PROTONS!!!

 

[evilbooyaa]

Booya, not sure I follow. All pts in POP-RT got ADT, with 20% getting permanent ADT (orchiectomy).

Sneaky thoughts:

I'm not sure the POP-RT results are what I see in my practice. There are too many "Regional with Distant Mets" after PORT compared to what I see.

My gut tells me the vast majority of biochem recurrences that I see are pelvic LN recurrences. Perhaps they followed pts differently than I do. Perhaps I am getting PET's sooner than POP-RT given their high rate of distant mets in pts initially staged as M0 with preRT PSMA. Perhaps their PET scanner is of lower quality. I don't know.

Once a pt has LN recurrence, I treat those patients with salvage pelvic XRT (notice I didn't say WPRT, another discussion for another day). I might salvage some, but more likely it delays progression in many to help keep them off ADT for longer.

Now I have avoided over radiating those who weren't going to benefit from WPRT in the first place and thereby halved that group's risk of RT toxicity and there is no known detriment to their overall survival probability.

I see a patient developed neuroendocrine dedifferentiation in the WPRT group - did WPRT influence that. What about higher 2nd malignancy risk in WPRT in a group of men where the majority are going to live over 10Y? Lots to digest.

View attachment 377435

I meant that adding WPRT improves BPFS, when all other variables are held standard (like RT dose, ADT, etc.) This holds in both super high risk (remember the cut-off for POP-RT was like 30-40% LN risk per Roach IIRC) and in salvage (RTOG 0534) based on certain PSA thresholds.

I'm skeptical of trials where adding ADT improves BPFS as a justification on its own, as otherwise we should be ADTing Gleason 6 PCA treated with RT.

The way I read the table you sent is as follows:

Enough of the PORT only patients had unaddressed pelvic nodal disease which grew after cessation of ADT and develop metastatic disease by the time it became visible enough on either PSA or PET/CT, however they did surveillance. This number was dramatically more than when the nodes were treated. Basically, the concept of 'microscopic disease in the nodes, when untreated, can seed additional distant mets given that's its not definitively treated'.

The issue with PORT only in that trial is that a significant proportion of those patients are no longer curable with salvage radiation, given the high rates of reigonal mets WITH distant mets. Your personal anecdotes about catching those patients when they're N1M0 are... just that. Even if you're catching them earlier on PSMA PET when they are radiographically N1M0 and 'salvaging' the fact that you don't think you're actually curing those folks and instead just kicking the ADT can down the road is a red flag in my eyes. Like they've already microscopically gone M1.

I would personally lean away from PORT only with a thought that they'll be salvageable based on the table you showed.

I presume by salvage pelvic XRT you mean SBRT to the involved node alone. Retrospective data suggetss bPFS and maybe MFS is better with salvage WPRT with SIB compared to SBRT alone without detriment in OS and expected increase in toxicity with elective nodal RT w/ SIB (https://www.europeanurology.com/article/S0302-2838(19)30533-0/fulltext) so there is no wrong answer, awaiting results of PEACE- V STORM for a prospective answer on that currently....

 

[tomhobbes]

I have a (IMO) relatively conservative urethra constraint when doing FLAME boosting. Boils down to point dose less than 105-107% of whatever Rx the whole prostate is getting.

Another data point here similar to Palex. High risks prostates, with fair GU function and moderate size prostate gland who are otherwise not undergoing combination beam+brachy, receive 60/20fx to the prostate and 44/20 to the nodes. Intraprostatic boost to 72/20fx with 63-64 Gy urethra PRV constraint. MRI obtained at time of sim in vac lok. Urethra contoured on MRI with 3 mm PRV. Bladder neck/prostate CTV interface - basically a superior extension of the urethra PRV, also constrained to 63 Gy. Agree with everyone else above that want to see concordance between biopsy and imaging to boost.

While the NRG GU 009 and 010 protocol boost with the 60/20fx regimen is 78Gy, have anecdotally seen mild acute GU sx at 75Gy so staying at 72Gy instead.

 

[SneakyBooger]

(remember the cut-off for POP-RT was like 30-40% LN risk per Roach IIRC) and in salvage (RTOG 0534) based on certain PSA thresholds.

I'm skeptical of trials where adding ADT improves BPFS as a justification on its own, as otherwise we should be ADTing Gleason 6 PCA treated with RT.

The way I read the table you sent is as follows:

Enough of the PORT only patients had unaddressed pelvic nodal disease which grew after cessation of ADT and develop metastatic disease by the time it became visible enough on either PSA or PET/CT, however they did surveillance. This number was dramatically more than when the nodes were treated. Basically, the concept of 'microscopic disease in the nodes, when untreated, can seed additional distant mets given that's its not definitively treated'.

The issue with PORT only in that trial is that a significant proportion of those patients are no longer curable with salvage radiation, given the high rates of reigonal mets WITH distant mets. Your personal anecdotes about catching those patients when they're N1M0 are... just that. Even if you're catching them earlier on PSMA PET when they are radiographically N1M0 and 'salvaging' the fact that you don't think you're actually curing those folks and instead just kicking the ADT can down the road is a red flag in my eyes. Like they've already microscopically gone M1.

I would personally lean away from PORT only with a thought that they'll be salvageable based on the table you showed.

I presume by salvage pelvic XRT you mean SBRT to the involved node alone. Retrospective data suggetss bPFS and maybe MFS is better with salvage WPRT with SIB compared to SBRT alone without detriment in OS and expected increase in toxicity with elective nodal RT w/ SIB (https://www.europeanurology.com/article/S0302-2838(19)30533-0/fulltext) so there is no wrong answer, awaiting results of PEACE- V STORM for a prospective answer on that currently....

POP-RT inclusion was >20% LN risk per Roach formula (median est. risk was 37.8%).

Median PSA 28.

Gleason Group 4-5 = 49%.

DFS benefit not seen for those >66YO and LN risk <40%.

DMFS benefit (unplanned subgroup analysis) not seen in >66YO.

Thanks for the article. Lots of ideas in there. I'm digging through it now. Do you have the supplement? I love supplements. A lot of good stuff is often hidden in the supplements. Maybe I missed it at the link you gave.

We each can have different take homes from that study.

Totally agree, no wrong answer. For me, I suspect the differences seen in regards to bDFS and MFS is more likely due to this: "the use of adjuvant ADT was not standardized for these patients, with a substantial difference in use of adjuvant ADT between both treatment groups (SBRT: 23% vs. ENRT: 60%)."

 

[evilbooyaa]

Fair enough - I think you have dissected POP-RT more than I have but the 30-40% risk was what I remembered which is inline with the DFS benefit at LN risk > 40%. And we know Roach over-estimates LN risk. I personally use MSKCC nomogram. I do need to look into how much it over-estimates compared to MSKCC

Link I posted has a supplemental word doc.

Sure, I'm not convinced on MFS benefit of ENI w/ SIB compared to SBRT in oligorecurrent nodal pCA (in part based on the discrepancy of ADT) which is why until PEACE V STORM (such a long acronym for a trial) I don't think there is a single 'right' answer. In that situation I've truly discussed pros/cons of both and done both based on patient's wishes.

But, for someone who has a high risk of microscopic disease up-front... I'm very wary of skipping pelvic nodal RT because I'm not convinced that 'salvage' is as good as first line.

 

[sirspamalot]

Nobody is doing WPRT with POP-RT regimen, I certainly am not.

The additional pelvic LN coverage with IMRT adds -minimal- toxicity and may help with the "hidden LN" problem that PSMA PET is uncovering.

Then again, maybe its all genetics and we need a better prognostic test, or better than what we have now anyway.

If breast is the wurst, then prostate is the ... sausage? Count me as more confused by the results than ever before.

That said, some feel moar is bettah and FLAME away. I am not at least for now, in elderly or compromised men, esp since salvage with SBRT seems pretty good.

If you're 45-55 and healthy, with very high grade focal disease, FLAME like SIB seems like the choice. Along with PSMA PET and pelvic nodal coverage (ducks)..

 

[A_DeMichele]

toxicity of elective pelvic nodal irradiation can be devastating. like permanent loss if QOL

 

[sirspamalot]

toxicity of elective pelvic nodal irradiation can be devastating. like permanent loss if QOL

Maybe WPRT but IMRT nodes?

Cmon now..

 

[A_DeMichele]

Maybe WPRT but IMRT nodes?

Cmon now..

With IMRT you can have localized hotspots in adjacent bowel that are worse than 4-field box

 

[dieABRdie]

With IMRT you can have localized hotspots in adjacent bowel that are worse than 4-field box

Our dosimetrists used to hate me (probably still do...), but I would send it back for any max dose over 56Gy, certainly in the bowel but also try to limit this through the lymph node volume. They've got it down now. It makes me feel all warm and fuzzy inside when I see the prescription dose colorwash nearly homogeneous in color without either bright spots or cold spots. And then the 30Gy isodose looks like a butterfly... its a thing of beauty.

On a related note... I feel like every patient I've ever seen who got neoadjuvant chemorads for rectal cancer and subsequently had horrible chronic, symptomatic proctitis... also got 3DCRT. But I haven't seen it yet with any patients that were treated with IMRT.

Maybe its just we haven't been using IMRT quite as long... but I was thinking it might be because any hot spots that occur with 3DCRT; are more likely to be "real" than those hot spots on an IMRT plan. An IMRT dose distribution will have so many more subfields or beamlets that make it up... so over a course of treatment the hot spot will be more "smeared" out compared to the plan on paper.

The 3D plan might have a lower absolute hot spot, but conversely might have a greater chance of manifesting the hot spot over a course of treatment... and thus might have higher toxicity?

Ex: the 60Gy max point dose in bowel; where basically its a tiny tail of 0.001cc of dose over 56Gy. Seems like it wouldn't actually happen in real life. But... it certainly looks bad on paper if they had a bad outcome. So I don't allow it unless absolutely necessary for coverage.

 

[sirspamalot]

G2/G3 numbers make it clear that IMRT for pelvic nodal coverage is of minimal impact.

One can certainly argue whether there is real value (does bDFS count any more?) with pelvic nodal coverage till the cows come home.. but no one can argue that toxicity is not the limiting factor.

 

[SneakyBooger]

G2/G3 numbers make it clear that IMRT for pelvic nodal coverage is of minimal impact.

One can certainly argue whether there is real value (does bDFS count any more?) with pelvic nodal coverage till the cows come home.. but no one can argue that toxicity is not the limiting factor.

POP-RT late toxicity 2X as high with pelvic IMRT...

 

[sirspamalot]

Cmon man.. you're citing WPRT results. OF COURSE WPRT has higher toxicity versus no WPRT.

But doing nodes with IMRT?

 

[drowsy12]

Cmon man.. you're citing WPRT results. OF COURSE WPRT has higher toxicity versus no WPRT.

But doing nodes with IMRT?

Looks like it was imrt in the POP TRIAL:


Inverse planning method was used to plan intensity-modulated radiotherapy (IMRT) with a fixed field, dynamic arc, or helical tomotherapy techniques, ensuring coverage of at least 95% of PTV within 95% prescription isodose. In WPRT arm, radiotherapy to pelvic nodes and prostate was delivered as a simultaneous integrated boost. One of the two authors (V.M. or U.M.) approved all the contours and treatment plans. Each finalized plan underwent patient-specific quality assurance for plan delivery before beginning the treatment course. Daily volumetric image guidance using on-board kilovoltage cone-beam CT or megavoltage CT was obtained to verify patient position.

 

[sirspamalot]

Yes, and here were the results re toxicity:

Acute GU and GI toxicities have been reported in detail earlier, which did not show any significant difference between the two arms.4 Late bowel and bladder toxicities were updated at median follow-up of 68 months (Table 2). Cumulative ≥ grade II late GU toxicity was significantly higher with WPRT (20.0% v 8.9%, P = .02), while no statistically significant difference was observed for ≥ grade II late GI toxicity (8.2% v 4.5%, P = .28). No RTOG grade IV GU or GI toxicity was observed in either of the arms.


So there is an increase in reported G2 GU toxicity. Welp, I've been doing this regimen for several years and am happy to say that for my population, many of whom have mild GU dysfuction already, there has been no obvious "doubling" of urinary difficulty. In fact, many patients have zero changes in their GU dysfunction.

YMMV.

 

[deleted1111261]

Yes, and here were the results re toxicity:

Acute GU and GI toxicities have been reported in detail earlier, which did not show any significant difference between the two arms.4 Late bowel and bladder toxicities were updated at median follow-up of 68 months (Table 2). Cumulative ≥ grade II late GU toxicity was significantly higher with WPRT (20.0% v 8.9%, P = .02), while no statistically significant difference was observed for ≥ grade II late GI toxicity (8.2% v 4.5%, P = .28). No RTOG grade IV GU or GI toxicity was observed in either of the arms.


So there is an increase in reported G2 GU toxicity. Welp, I've been doing this regimen for several years and am happy to say that for my population, many of whom have mild GU dysfuction already, there has been no obvious "doubling" of urinary difficulty. In fact, many patients have zero changes in their GU dysfunction.

YMMV.

My experience is same

 

[sirspamalot]

For anyone wondering how that can be... simply google:

"Assessment of Prostate Cancer Patients Understanding of the IPSS Questionnaire" Redirecting

Results: In terms of overall IPSS score, 61 men (42%) had a lower/improved IPSS after nurse verification and 9 men (6%) had a higher/worsened IPSS. Prior to verification, patients overstated their symptoms of frequency, intermittency, and incomplete emptying.

 

[evilbooyaa]

With IMRT you can have localized hotspots in adjacent bowel that are worse than 4-field box

Not if you constrain it properly.... I mandate small bowel to get point dose < 105% of whatever the PTV nearest to it is. Constraining bowel to 56Gy when you're giving 50.4Gy is silly.

Also less of an issue if you give 45/25 (or equivalent) to your nodal volumes rather than 50/25 or 50.4/28.

I'm otherwise a bit confused - when people say WPRT, for prostate (or gynecologic) cancer, in 2023, is anyone talking about 3D-CRT? We're all talking about IMRT, right? Nobody is doing 4-field boxes for prostate anymore, right? We've all learned and moved on from doing pelvic nodal irradiation using a 4-field box?

I KNOW some are still doing 4-field box for defijnitive cervix routinely which is its own frustration but not the topic of this thread.

 

[SneakyBooger]

WPRT = IMRT. I wouldn't do 3DCRT on my own pelvis, so not gonna do it in a patient...

 

[sirspamalot]

Your pelvis thanks you kindly

 

[ramsesthenice]

Not if you constrain it properly.... I mandate small bowel to get point dose < 105% of whatever the PTV nearest to it is. Constraining bowel to 56Gy when you're giving 50.4Gy is silly.

Also less of an issue if you give 45/25 (or equivalent) to your nodal volumes rather than 50/25 or 50.4/28.

I'm otherwise a bit confused - when people say WPRT, for prostate (or gynecologic) cancer, in 2023, is anyone talking about 3D-CRT? We're all talking about IMRT, right? Nobody is doing 4-field boxes for prostate anymore, right? We've all learned and moved on from doing pelvic nodal irradiation using a 4-field box?

I KNOW some are still doing 4-field box for defijnitive cervix routinely which is its own frustration but not the topic of this thread.

With you 100% bud. Have to look at the plans closely. If I’m boosting a gross node to 54-60, then taking higher doses to small volumes of bowel will be fine. But my elective nodal volumes (which I only do for N+ or folks with 2 high risk features) go to 45, not 50.4. The bother thing I do 100% of the time is personally contour out the sigmoid so that we don’t artificially under dose gross disease because they are trying to limit dose the the “bowel bag”. It’s not always as easy as one would think to delineate the sigmoid from small bowel in the lower abdomen if it’s good and empty.

Speaking of, I don’t get super aggressive with bowel preps. Use to do it to get better dosimetry but have come to see some people are just naturally full of s*** and won’t match up with reality if you do too much at sim.

 

[sirspamalot]

won’t match up with reality if you do too much at sim.

Words to CT sim by indeed.

I've long since abandoned any 'do this before sim' except please don't pee right before you go in. We'll figure it out after we scout scan you where you're at and if you're full of it, we'll have to begin the regimen grind to get you where you needt to be...

80% are okay day 1
15% need some meds and coaching
5% are very difficult, not really sure they're doing as they're told, and yessir they get the hose (RRC)

 

[evilbooyaa]

With you 100% bud. Have to look at the plans closely. If I’m boosting a gross node to 54-60, then taking higher doses to small volumes of bowel will be fine. But my elective nodal volumes (which I only do for N+ or folks with 2 high risk features) go to 45, not 50.4. The bother thing I do 100% of the time is personally contour out the sigmoid so that we don’t artificially under dose gross disease because they are trying to limit dose the the “bowel bag”. It’s not always as easy as one would think to delineate the sigmoid from small bowel in the lower abdomen if it’s good and empty.

Speaking of, I don’t get super aggressive with bowel preps. Use to do it to get better dosimetry but have come to see some people are just naturally full of s*** and won’t match up with reality if you do too much at sim.

I see no rationale of taking pelvic nodes to > 45Gy.

I think CC constraints to bowel bag is stupid. The constraints were for bowel loops but people draw bag b/c it's easier. I have lower dose (25-30Gy) constraints based on bowel bag as a percentage, but drawing sigmoid separately from bowel bag very reasonable as well.

Bowel prep should be simple and reproducible. 'Daily enema' is a hard no.