High Risk Prostate - GETUG 18 - Conventional fractionation - Improved OS

[SneakyBooger]

Conventional EBRT to 80 Gy with 3 yrs ADT improves OS in high risk prostate ca.

Overall survival was improved, ergo a surrogate for OS in prostate radiotherapy not needed.

I imagine these results are going to stir the pot in the rad onc community.

Conventional fractionation has the data. Hypofractionation does not - would "not be proper to do so".

Hats off to the French.

ASCO GU 2024 GETUG 18

The abstract:

ASCO 2024

Long-term results of dose escalation (80 vs 70 Gy) combined with long-term androgen deprivation in high-risk prostate cancers: GETUG-AFU 18 randomized trial.

Christophe Hennequin, Paul Sargos, Lise Roca, Marlon Silva, Igor Latorzeff, Didier Peiffert, Salvatore Cozzi, Ahmed Benyoucef, Ali Hasbini, Stephane Supiot, Philippe Ronchin, Thierry Wachter, David Azria, Pierre-Etienne Cailleux, Luc Cormier, Mallik Zibouche, Gr´egoire Pign´e, French Genito-Urinary Tumours Study Group (GETUG); Department of Radiation Oncology, Saint-Louis Hospital, Paris, France; Department of Radiation Oncology, Institut Bergoni´e, Bordeaux, France; Montpellier Cancer Institute, Montpellier, France; Centre François Baclesse, Caen, France; Groupe Oncorad Garonne, Toulouse, France; Cancer Institute of Lorraine, Vandœuvre-L`esNancy, France; Leon Berard Cancer Center, Lyon, France; Henri Becquerel Center, Rouen, France; Finisterian Center of Radiotherapy and Oncology, Brest, France; Institut de Canc´erologie de l’Ouest, Saint Herblain, France; Azur´een Center of Oncology, Mougins, France; Regional University Hospital of Orl´eans, Orl´eans, France; Department of Radiation Oncology, Montpellier Cancer Institute ICM, Montpellier, France; Oncology and Radiotherapy Center 37, Chambray -Les-Tours, France; University Hospital of Dijon - Urology, Dijon, France; Unicancer - GETUG Groupe, Paris, France; University Institute of Cancerology and Hematology of Saint-Etienne, Saint-Etienne, France

Background: Radiotherapy (RT) delivered in combination with androgen deprivation therapy (ADT) improve survival for patients with prostate adenocarcinoma. RT given at a dose of 80 Gy is generally well tolerated but the occurrence of grade 3-4 toxicities is significantly more frequent than at a dose of 70 Gy. Furthermore, ADT has been reported to increase RT-related toxicity. Thus, we aimed to evaluate the efficacy and safety of dose escalation in combination with long term ADT in high-risk prostate cancer patients.

Methods: The GETUG-AFU 18 study, sponsored by Unicancer, is a phase III randomized trial. Eligible patient had high-risk (cT3-T4 or PSA ≥ 20 ng/ml or Gleason score ≥ 8-10) prostate adenocarcinoma with negative lymph nodes status on CT-scan or MRI. Patients were randomly assigned to dose-escalated RT (80 Gy) or conventional-dose (70 Gy) with 3 years of ADT in both arms. Randomization (1:1) was stratified on pelvic lymph-nodes dissection (PLND; yes or no) and institution. Pelvic nodal irradiation (46 Gy) was performed for all patients except in case of negative PLND. The primary endpoint is the biochemical or clinical progression-free survival (bcPFS) at 5 years following ASTRO-Phoenix definition. Secondary endpoints are overall survival (OS), acute and late toxicity (CTCAE v3), and quality of life. To improve bcPFS from 65 to 75% (Hazard Ratios

---

= 0.67), 500 patients were required (a= 5% and 1-b= 80%) with 197 events at 5 years.

Results: 505 patients were included between June 2009 and January 2013. Main characteristics of the population were median age of 70.6 years (range 52-80); 268 (53.1%) patients with a Gleason score ≥ 8; median PSA value of 13.8 ng/ml (0.4-109.9); 62.3% of patient with cT3, and 16.4% with PLND. There was no imbalance between groups for major prognostic factors. The bcPFS was significantly improved in the dose-escalated RT arm compared with conventional RT arm (HR = 0.56, [95% CI, 0.40-0.76], p = 0.0005). The 5-year bcPFS was 91.4% (95% CI, 87.0-94.4) and 88.1% (95% CI, 83.2-91.6), and the 7-year bcPFS 88.1% (95% CI, 83.1-91.7) and 79.2% (95% CI, 73.1-84.0) in dose-escalated RT and conventional RT, respectively. We did observe significant differences in prostate cancer-specific survival (HR = 0.48 [95% CI, 0.27-0.83], p = 0.0090) and overall survival (HR = 0.61 [95% CI, 0.44-0.85], p = 0.0039). No prognostic factors were identified for bcPFS. Regarding late toxicities, there was no significant difference between arms with 78.2% and 76.1% of ≥Grade 2 toxicity with dose-escalated RT and conventional RT, respectively.

Conclusions: Dose-escalation RT in combination with longterm ADT is effective and safe, increasing not only the bcPFS rate but also specific survival and overall survival in high-risk prostate cancer patients without increasing long-term toxicity. Clinical trial information: NCT00967863. Research Sponsor: French National Cancer Institute; French National Cancer League; AstraZeneca.

ASCO GU 2024: Long-Term Results of Dose Escalation (80 vs 70 Gy) Combined with Long-Term Androgen Deprivation in High-Risk Prostate Cancer: GETUG-AFU 18 Randomized Trial

ASCO GU 2024 long-term results of the GETUG-AFU 18, androgen deprivation in high-risk prostate cancer, MARCAP meta-analysis, ADT in high-risk prostate cancer patients, pelvic lymph node dissection.

www.urotoday.com

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[Burt Radnolds]

Conventional EBRT to 80 Gy with 3 yrs ADT improves OS in high risk prostate ca.

Overall survival was improved, ergo a surrogate for OS in prostate radiotherapy not needed.

I imagine these results are going to stir the pot in the rad onc community.

Conventional fractionation has the data. Hypofractionation does not - would "not be proper to do so".

Hats off to the French.

ASCO GU 2024 GETUG 18

The abstract:

ASCO 2024

Long-term results of dose escalation (80 vs 70 Gy) combined with long-term androgen deprivation in high-risk prostate cancers: GETUG-AFU 18 randomized trial.

Christophe Hennequin, Paul Sargos, Lise Roca, Marlon Silva, Igor Latorzeff, Didier Peiffert, Salvatore Cozzi, Ahmed Benyoucef, Ali Hasbini, Stephane Supiot, Philippe Ronchin, Thierry Wachter, David Azria, Pierre-Etienne Cailleux, Luc Cormier, Mallik Zibouche, Gr´egoire Pign´e, French Genito-Urinary Tumours Study Group (GETUG); Department of Radiation Oncology, Saint-Louis Hospital, Paris, France; Department of Radiation Oncology, Institut Bergoni´e, Bordeaux, France; Montpellier Cancer Institute, Montpellier, France; Centre François Baclesse, Caen, France; Groupe Oncorad Garonne, Toulouse, France; Cancer Institute of Lorraine, Vandœuvre-L`esNancy, France; Leon Berard Cancer Center, Lyon, France; Henri Becquerel Center, Rouen, France; Finisterian Center of Radiotherapy and Oncology, Brest, France; Institut de Canc´erologie de l’Ouest, Saint Herblain, France; Azur´een Center of Oncology, Mougins, France; Regional University Hospital of Orl´eans, Orl´eans, France; Department of Radiation Oncology, Montpellier Cancer Institute ICM, Montpellier, France; Oncology and Radiotherapy Center 37, Chambray -Les-Tours, France; University Hospital of Dijon - Urology, Dijon, France; Unicancer - GETUG Groupe, Paris, France; University Institute of Cancerology and Hematology of Saint-Etienne, Saint-Etienne, France

Background: Radiotherapy (RT) delivered in combination with androgen deprivation therapy (ADT) improve survival for patients with prostate adenocarcinoma. RT given at a dose of 80 Gy is generally well tolerated but the occurrence of grade 3-4 toxicities is significantly more frequent than at a dose of 70 Gy. Furthermore, ADT has been reported to increase RT-related toxicity. Thus, we aimed to evaluate the efficacy and safety of dose escalation in combination with long term ADT in high-risk prostate cancer patients.

Methods: The GETUG-AFU 18 study, sponsored by Unicancer, is a phase III randomized trial. Eligible patient had high-risk (cT3-T4 or PSA ≥ 20 ng/ml or Gleason score ≥ 8-10) prostate adenocarcinoma with negative lymph nodes status on CT-scan or MRI. Patients were randomly assigned to dose-escalated RT (80 Gy) or conventional-dose (70 Gy) with 3 years of ADT in both arms. Randomization (1:1) was stratified on pelvic lymph-nodes dissection (PLND; yes or no) and institution. Pelvic nodal irradiation (46 Gy) was performed for all patients except in case of negative PLND. The primary endpoint is the biochemical or clinical progression-free survival (bcPFS) at 5 years following ASTRO-Phoenix definition. Secondary endpoints are overall survival (OS), acute and late toxicity (CTCAE v3), and quality of life. To improve bcPFS from 65 to 75% (Hazard Ratios

---

= 0.67), 500 patients were required (a= 5% and 1-b= 80%) with 197 events at 5 years.

Results: 505 patients were included between June 2009 and January 2013. Main characteristics of the population were median age of 70.6 years (range 52-80); 268 (53.1%) patients with a Gleason score ≥ 8; median PSA value of 13.8 ng/ml (0.4-109.9); 62.3% of patient with cT3, and 16.4% with PLND. There was no imbalance between groups for major prognostic factors. The bcPFS was significantly improved in the dose-escalated RT arm compared with conventional RT arm (HR = 0.56, [95% CI, 0.40-0.76], p = 0.0005). The 5-year bcPFS was 91.4% (95% CI, 87.0-94.4) and 88.1% (95% CI, 83.2-91.6), and the 7-year bcPFS 88.1% (95% CI, 83.1-91.7) and 79.2% (95% CI, 73.1-84.0) in dose-escalated RT and conventional RT, respectively. We did observe significant differences in prostate cancer-specific survival (HR = 0.48 [95% CI, 0.27-0.83], p = 0.0090) and overall survival (HR = 0.61 [95% CI, 0.44-0.85], p = 0.0039). No prognostic factors were identified for bcPFS. Regarding late toxicities, there was no significant difference between arms with 78.2% and 76.1% of ≥Grade 2 toxicity with dose-escalated RT and conventional RT, respectively.

Conclusions: Dose-escalation RT in combination with longterm ADT is effective and safe, increasing not only the bcPFS rate but also specific survival and overall survival in high-risk prostate cancer patients without increasing long-term toxicity. Clinical trial information: NCT00967863. Research Sponsor: French National Cancer Institute; French National Cancer League; AstraZeneca.

ASCO GU 2024: Long-Term Results of Dose Escalation (80 vs 70 Gy) Combined with Long-Term Androgen Deprivation in High-Risk Prostate Cancer: GETUG-AFU 18 Randomized Trial

ASCO GU 2024 long-term results of the GETUG-AFU 18, androgen deprivation in high-risk prostate cancer, MARCAP meta-analysis, ADT in high-risk prostate cancer patients, pelvic lymph node dissection.

www.urotoday.com

Moderate Hypofractionation in High-Risk, Organ-Confined Prostate Cancer: Final Results of a Phase III Randomized Trial - PubMed

Purpose To report the final results on treatment outcomes of a randomized trial comparing conventional and hypofractionated radiotherapy in high-risk, organ-confined prostate cancer (PCa). Patients and Methods This single-institution, randomized clinical trial, conducted from January 2003 to...

pubmed.ncbi.nlm.nih.gov

 

[SneakyBooger]

Moderate Hypofractionation in High-Risk, Organ-Confined Prostate Cancer: Final Results of a Phase III Randomized Trial - PubMed

Purpose To report the final results on treatment outcomes of a randomized trial comparing conventional and hypofractionated radiotherapy in high-risk, organ-confined prostate cancer (PCa). Patients and Methods This single-institution, randomized clinical trial, conducted from January 2003 to...

pubmed.ncbi.nlm.nih.gov

That was a negative trial.

Hypothesis generating only.

 

[Pointless]

What is the fractionation? I can't find anywhere other than 70 vs 80. It sounds to me like 70 by 2 Gy fractions? In which case, this is study adds nothing to the existing literature; we already know 70/2 is insufficient. We've known that for 15 years or more. If 70 in 28, then this trial has my attention.

 

[SneakyBooger]

we already know 70/2 is insufficient.

Not with regards to overall survival...

 

[ramsesthenice]

It’s randomized with a lot of patients so hats off to them for doing it. I’m not completely discounting the OS data, but there is something a little funny here. At both 5 and 10 years, there was a bigger difference in OS than PFS. That’s a little hard to explain if it’s a tumor control difference as biochemical failure should precede death from prostate cancer by quite a while. Not entirely sure how to conceptualize this. Hopefully the full publication may help answer some of these questions.

 

[SneakyBooger]

It’s randomized with a lot of patients so hats off to them for doing it. I’m not completely discounting the OS data, but there is something a little funny here. At both 5 and 10 years, there was a bigger difference in OS than PFS. That’s a little hard to explain if it’s a tumor control difference as biochemical failure should precede death from prostate cancer by quite a while. Not entirely sure how to conceptualize this. Hopefully the full publication may help answer some of these questions.

These results are certainly going to "shake up" the rad onc community...

 

[SneakyBooger]

Props to @Palex80

 

[Pointless]

Yeah but..... no. This doesn't look like a conventional vs hypofrac trial, it looks like a conventional dose escalation trial. Those are not the same things.

I take it you are a die hard conventional fx guy?

 

[communitydoc13]

What is the fractionation?

It would be 70/2 as this was conventional at initiation of the trial.

Not with regards to overall survival...

I agree...we have not seen survival benefit with dose escalation before, we know dose escalation results in biochemical progression free survival benefit but have not seen this manifested as an OS benefit.

I do agree with your conclusion to treat 80/40 + ADT as standard...but, I do not believe that the OS results are driven by prostate outcomes for all the same concerns that @ramsesthenice mentions above.

IMO, the problem is the variance in time to death for 70-year-old men naturally. This variance is large (huge number of men dying between 5 and 20 years from their 70th birthday without a sharp peak. When you are treating a disease process that is fairly likely to kill within 2-5 years (metastatic disease or other cancers), you can fairly easily prove survival benefit. When you are treating a disease where cause specific deaths may peak 10 years after diagnosis, it is close to impossible.

 

[SneakyBooger]

I take it you are a die hard conventional fx guy?

Until we have data with hypofrac showing OS benefit, yes, call me "Die Hard"!

 

[Pointless]

Right. that's fine. I am happy to see that dose escalation, which we have been providing here in the US for at least a decade, also seems to impact OS. What I don't agree with, and what the OP seems to be suggesting, is that 80 by 2's is better than hypofractionation. This trial does not support that conclusion. 70 in 28 is essentially equivalent to 80 by 2's in EQD2.

Either willful ignorance or completely disingenuous to try and use this trial to justify continuing to conventionally fractionate over hypofrac IMO.

 

[SneakyBooger]

what the OP seems to be suggesting, is that 80 by 2's is better than hypofractionation.

You are putting words in my mouth...

I am simply saying we have level 1 evidence of a survival advantage with conventional fractionation.

 

[SneakyBooger]

Either willful ignorance or completely disingenuous

Given what we know thus far regarding GETUG 18, I can easily see an argument that using anything other than conventional fractionation in high risk prostate cancer could be construed as "nonperformance of duty".

 

[drowsy12]

Right. that's fine. I am happy to see that dose escalation, which we have been providing here in the US for at least a decade, also seems to impact OS. What I don't agree with, and what the OP seems to be suggesting, is that 80 by 2's is better than hypofractionation. This trial does not support that conclusion. 70 in 28 is essentially equivalent to 80 by 2's in EQD2.

Either willful ignorance or completely disingenuous to try and use this trial to justify continuing to conventionally fractionate over hypofrac IMO.

Yep.

 

[Ray D. Ayshun]

Quite the rollercoaster. I went from thinking that 80/40 showed an OS advantage over 70/28 to realizing it's 80/40 over 70/35, which in turn means there was no reason for me to ever hear about GETUG 18. I supposed it's a nice reminder for the academic rad oncs that photon radiation does more than cause toxicities, but I already believed that.

 

[MidwestRadOnc]

If a patient comes to you with a PSA of 7, grade group 2, but you get an MRI and there is ECE, is this a T3 and thus high risk per trial? Can you convince evicore to let you treat 80/40 without treating nodes in this case?

T staging in prostate annoys me. I no longer do DREs. MRI is better, but can I use it to technically t stage?

 

[SneakyBooger]

If a patient comes to you with a PSA of 7, grade group 2, but you get an MRI and there is ECE, is this a T3 and thus high risk per trial? Can you convince evicore to let you treat 80/40 without treating nodes in this case?

T staging in prostate annoys me. I no longer do DREs. MRI is better, but can I use it to technically t stage?

Yes, through appeal.

Yes, I will use MRI to stage.

 

[MidwestRadOnc]

Yes, through appeal.

Yes, I will use MRI to stage.

So bilateral disease is not uncommon on biopsy or MRI and DRE is subjective and misses most of the prostate. That’s a high risk factor, but is that from DRE only - that’s the argument I would expect.

 

[Ray D. Ayshun]

If a patient comes to you with a PSA of 7, grade group 2, but you get an MRI and there is ECE, is this a T3 and thus high risk per trial? Can you convince evicore to let you treat 80/40 without treating nodes in this case?

T staging in prostate annoys me. I no longer do DREs. MRI is better, but can I use it to technically t stage?

In trying to interpret how to stage using NCCN I noticed this:

mpMRI can be used in the staging and characterization of prostate cancer. mpMRI images are defined as images acquired with at least one more sequence in addition to the anatomical T2-weighted images, such as DWI or dynamic contrast-enhanced (DCE) images.mpMRImay be used to better risk stratify patients who are considering active surveillance. Additionally, mpMRI may detect large and poorly differentiated prostate cancer (Grade Group ≥2) and detect extracapsular extension (T staging) and is preferred over CT for abdominal/pelvic staging. mpMRI has been shown to be equivalent to CT scan for pelvic lymph node evaluation.

Technically, I think T staging is based on DRE because that's what we've always been told. On the other hand, based on the NCCN guidelines as a whole, it seems reasonable to use ECE on mpMRI as justification for calling a patient high risk. Seems more reliable than a DRE anyway.

 

[Pointless]

You are putting words in my mouth...

I am simply saying we have level 1 evidence of a survival advantage with conventional fractionation.

View attachment 381676

OK, but here are the words that came out of your mouth:

Conventional fractionation has the data. Hypofractionation does not - would "not be proper to do so".

Props to @Palex80



View attachment 381674

 

[TheWallnerus]

What I don't agree with, and what the OP seems to be suggesting, is that 80 by 2's is better than hypofractionation. This trial does not support that conclusion. 70 in 28 is essentially equivalent to 80 by 2's in EQD2.

Point of order

If high risk prostate cancer has an alpha/beta in the 5 range, or higher, and it absolutely could just based on the wide confidence intervals we have for prostate alpha/beta in general (and a radiobiological principle that the alpha/beta of “aggressive” faster growing tumors is >>3), then bringing up hypofractionation here is a mathematically moot point… mooter and mooter the higher the alpha/beta or the more uncertain we are about the alpha/beta.

 

[theradiator]

For the good of the field, we should declare 80 Gy in 40 fractions as victory over high risk prostate cancer and move on. As a member of a specialty that lists 20 different radiation schedules as 'standard of care' on NCCN guidelines, of course we will not do that and thus chaos ensues.

Urologists (who by the way have brilliantly controlled their numbers) have declared robotic surgery their standard of care without showing any survival advantage over laparoscopic or open prostatectomy and march with a unified narrative against us.

 

[TheWallnerus]

Urologists (who by the way have brilliantly controlled their numbers)

 

[SneakyBooger]

 

[SneakyBooger]

 

[MidwestRadOnc]

For the good of the field, we should declare 80 Gy in 40 fractions as victory over high risk prostate cancer and move on. As a member of a specialty that lists 20 different radiation schedules as 'standard of care' on NCCN guidelines, of course we will not do that and thus chaos ensues.

Urologists (who by the way have brilliantly controlled their numbers) have declared robotic surgery their standard of care without showing any survival advantage over laparoscopic or open prostatectomy and march with a unified narrative against us.

Urologists get cryo paid for FFS

 

[MidwestRadOnc]

View attachment 381683
View attachment 381684

This is basically a plot of the financial health of each specialty. Is rad onc a worse dumpster fire than EM? It’s close.

There is a reason that the FIRE forums online are heavily populated by EM and gas MDs.

 

[Palex80]

Here at the data.

80 vs. 70 Gy

PFS at 5 years: 91.4% vs. 88.1%
PFS at 10 years: 83.6% vs. 72.2%

OS at 5 years: 93.4% vs 88.7%
OS at 10 years: 77% vs. 65.9%

Very important: The definition of PFS in GETUG-18 is not the "classic" PFS definition. Classic PFS-definition includes deaths as events. And that would obviously mean than the numbers posted above would not work out, since OS is lower than PFS at 10 years.
In GETUG-18, PFS-events were only biochemical or clinical progressions, but not deaths.

Despite that, it appears very unlikely that a 3.3% difference in progressions at 5 years would translate to 11.1% difference in survival at 10 years. Which likely means that: An extra 10 Gy on the anterior rectal wall reduces the risk of death by cardiovascular disease after 10 years.

 

[elementaryschooleconomics]

This is the best thing that has happened in RadOnc in at least a year, maybe two.

Up next:

1) Editorials from "KOLs" basically rehashing the SDN conversation, but in journals.
2) Editorials and retrospective studies tying these results to DEI.
3) Financial toxicity papers using these results...my guess is there will be at least one calculating a "cost per percent improvement in PFS", and the conclusion will not-so-subtly hint that "it's not worth it".
4) Something from the proton crew, really reaching to craft a paper that says "protons good".
5) Something from the goo crew, probably simulating what the toxicity profile might have looked like had they injected patients with the goo, all completely imaginary, overtly concluding the goo should be used for every prostate patient, everywhere, always. All authors will be receiving some kind of payment from Boston Scientific and/or Palette.

Did I miss anything?

 

[SneakyBooger]

Rad Onc: "Oh no. No, no, no it isn't. What's the time? I want to go home early"

 

[A_DeMichele]

What does this study say about the need for nodal irradiation in high risk PCa?

 

[evilbooyaa]

What does this study say about the need for nodal irradiation in high risk PCa?

? Nothing? Since basically all patients got ENI to 46Gy, unless they had a negative node dissection (how many patients would that have been??)

To OP:

This is the first time that dose escalation has improved OS. That is note worthy of this trial. Previous studies have shown bPFS, maybe DMFS improvements with dose escalation. So, cool in that sense.

There is nothing in the paper that suggests conventional fx is better than mod hypo.

70Gy in 2Gy/fx is a lower dose than usual standard in anything beyond like the 2010s or later? Idk the last time a prostate patient was 'definitively' treated to 70Gy in 35 fractions.

And that's without the questions about OS benefit. Of course Rad Oncs will twist themselve sinto pretzels to deny that anything they do improves OS, but I get the concern.

That being said, how does this influence my practice? It doesn't. I would never do 70Gy in 35 fractions for prostate cancer, and I will continue to not do so.

There are lots of reasons to favor conventional fx over mod hypo fx. This ain't it, chief.

 

[MidwestRadOnc]

? Nothing? Since basically all patients got ENI to 46Gy, unless they had a negative node dissection (how many patients would that have been??)

To OP:

This is the first time that dose escalation has improved OS. That is note worthy of this trial. Previous studies have shown bPFS, maybe DMFS improvements with dose escalation. So, cool in that sense.

There is nothing in the paper that suggests conventional fx is better than mod hypo.

70Gy in 2Gy/fx is a lower dose than usual standard in anything beyond like the 2010s or later? Idk the last time a prostate patient was 'definitively' treated to 70Gy in 35 fractions.

And that's without the questions about OS benefit. Of course Rad Oncs will twist themselve sinto pretzels to deny that anything they do improves OS, but I get the concern.

That being said, how does this influence my practice? It doesn't. I would never do 70Gy in 35 fractions for prostate cancer, and I will continue to not do so.

There are lots of reasons to favor conventional fx over mod hypo fx. This ain't it, chief.

I know a doctor who does 70/35 with an SIB to tumor nodule. Not sure where that is coming from.

 

[Palex80]

I know a doctor who does 70/35 with an SIB to tumor nodule. Not sure where that is coming from.

FLAME had a higher dose. I presume he's adopting a more "safe" approach.

? Nothing? Since basically all patients got ENI to 46Gy, unless they had a negative node dissection (how many patients would that have been??)

14% had a node dissection and pN0, according to the slides.

 

[MidwestRadOnc]

FLAME had a higher dose. I presume he's adopting a more "safe" approach.


14% had a node dissection and pN0, according to the slides.

But the data is very clear you can escalate the WHOLE prostate not just the tumor beyond 70/35.

My personal “safe” conventional regimen without spacer is 81/45 with sib to 85.5

I’m less of a fan of 2.2 gy to the whole prostate x 35 (flame regimen before boost) which is really pushing the limits of what conventional frac is.

 

[evilbooyaa]

FLAME had a higher dose. I presume he's adopting a more "safe" approach.


14% had a node dissection and pN0, according to the slides.

More common of a procedure than I would have imagined...

Were the 14% all in one group versus the other? If balanced equally, then it still won't tell us anything about ENI in prostate cancer...

I know a doctor who does 70/35 with an SIB to tumor nodule. Not sure where that is coming from.

That's... not the right answer. But yes, hopefully that singular person listens to this practice changing study...

But the data is very clear you can escalate the WHOLE prostate not just the tumor beyond 70/35.

My personal “safe” conventional regimen without spacer is 81/45 with sib to 85.5

I’m less of a fan of 2.2 gy to the whole prostate x 35 (flame regimen before boost) which is really pushing the limits of what conventional frac is.

I personally stop at 79.2/44 with SIB to > 100Gy based on equivalent EQD2 a/b3 (for toxicity) from FLAME. Goal is isotoxic therapy. I don't change my constraints from what I'd accept for 79.2 and there is a urethral constraint added in and we accept whatever coverage we can based on anatomy...

 

[seper]

this study would have had better outcomes if nodal irradiation was optional

 

[Palex80]

Were the 14% all in one group versus the other? If balanced equally, then it still won't tell us anything about ENI in prostate cancer...

I stand corrected, it was 16.4% pN0
16.1% in the 70 Gy group and 16.8% in the 80 Gy group.

this study would have had better outcomes if nodal irradiation was optional

Toxicity-wise, indeed.

 

[evilbooyaa]

But the data is very clear you can escalate the WHOLE prostate not just the tumor beyond 70/35.

My personal “safe” conventional regimen without spacer is 81/45 with sib to 85.5

I’m less of a fan of 2.2 gy to the whole prostate x 35 (flame regimen before boost) which is really pushing the limits of what conventional frac is.

Sorry, this is bothering me more than it should. 85.5/45 is 1.9Gy/fx. That's not even a SIB. Just try going higher. Draw the urethra on the MRI you're (hopefully) using as part of your boost delineation. Limit that to a point dose of < 105-107% of whatever your whole gland dose is. Don't change what you accept on bladder/rectum. I promise you it will be OK. IMRT is a hell of a thing as we can see with SBRT planning. I promise the VMAT plan will do OK.

 

[mheat3]

Sorry, this is bothering me more than it should. 85.5/45 is 1.9Gy/fx. That's not even a SIB. Just try going higher. Draw the urethra on the MRI you're (hopefully) using as part of your boost delineation. Limit that to a point dose of < 105-107% of whatever your whole gland dose is. Don't change what you accept on bladder/rectum. I promise you it will be OK. IMRT is a hell of a thing as we can see with SBRT planning. I promise the VMAT plan will do OK.

What dose do you aim for the SIB?

 

[MidwestRadOnc]

Sorry, this is bothering me more than it should. 85.5/45 is 1.9Gy/fx. That's not even a SIB. Just try going higher. Draw the urethra on the MRI you're (hopefully) using as part of your boost delineation. Limit that to a point dose of < 105-107% of whatever your whole gland dose is. Don't change what you accept on bladder/rectum. I promise you it will be OK. IMRT is a hell of a thing as we can see with SBRT planning. I promise the VMAT plan will do OK.

Well the majority of rad oncs out there are still just treating the whole prostate to 79.4/44 or 70/28 without a focal boost. And we know that works well and is tolerated well. MSK data went to about what I'm doing now.
I don't have spacer available in majority of patients and most of these lesions are posterior. I delineate urethra (as best I can) and constrain a 2mm PRV (with much tighter constraints than yours). Haven't been comfortable doing more than my "gentle" regimen of pushing more dose into the tumor and putting hot spots in it.

Without fiducial markers, I'm not extremely confident in daily soft tissue matching off of cone beam especially with hip implants. I instruct therapists as best I can but it's still all over the place. I may start going to 2 Gy/fx (that's 90 Gy we are talking about a few mm from the rectum!). And we all know the variation in bladder and rectum from sim to daily treatments. What you plan to is not going to be what's delivered. The goal is to get as close as possible, but it's not an exact science in this anatomic region.

This is a medicolegal area I'm not extremely thrilled to wade too deeply into.

With fiducials and spacer, my preferred method of dose escalation (in high risk) is actually SBRT boost. I use this protocol: PROstate Multicentre External beam radioTHErapy Using a Stereotactic boost: the PROMETHEUS study protocol - PubMed

 

[grenz]

Sorry, this is bothering me more than it should. 85.5/45 is 1.9Gy/fx. That's not even a SIB. Just try going higher. Draw the urethra on the MRI you're (hopefully) using as part of your boost delineation. Limit that to a point dose of < 105-107% of whatever your whole gland dose is. Don't change what you accept on bladder/rectum. I promise you it will be OK. IMRT is a hell of a thing as we can see with SBRT planning. I promise the VMAT plan will do OK.

Do you get a fresh MRI if the patient has been on neoadjuvant ADT? The issue I ran into recently was I got a planning MRI after 8 weeks of neoadjuvant ADT, and the lesions were now PIRADS 3 and prostate had shrunk. Couldn’t use the new MRI for GTV delineation bc they were indistinct and couldn’t use the old one either because the gland had shrunk. N=1 but it discouraged me from doing this routinely

 

[ramsesthenice]

Do you get a fresh MRI if the patient has been on neoadjuvant ADT? The issue I ran into recently was I got a planning MRI after 8 weeks of neoadjuvant ADT, and the lesions were now PIRADS 3 and prostate had shrunk. Couldn’t use the new MRI for GTV delineation bc they were indistinct and couldn’t use the old one either because the gland had shrunk. N=1 but it discouraged me from doing this routinely

Interesting. I suspect it had more to do with the quality of the MRI. More often than not, on a standard T2, treated lesions don't look that different. DWI is much more efficient at identifying treated tumor. But you raise an interesting issue. Personally, I don't think we are as good at delineating the DIL as we think, and I don't obsess over the issue. Instead, when able, I try to more or less divy up the prostate into quadrants and boost as much of the involved quadrant as I can. Is it the right thing to do? I don't know. But I've been able to do it isotoxically and am pretty happy with it.

 

[communitydoc13]

Do you get a fresh MRI if the patient has been on neoadjuvant ADT?

I do. Prostate shrinkage is often substantial. Regarding boost target? Agree with above that refined delineation is often hard (sometimes you get a beautiful area abutting the capsule that is your highest Gleason disease, but I would consider exception rather than rule).

 

[grenz]

I do. Prostate shrinkage is often substantial. Regarding boost target? Agree with above that refined delineation is often hard (sometimes you get a beautiful area abutting the capsule that is your highest Gleason disease, but I would consider exception rather than rule).

Sounds like everyone is not aiming for perfection with GTV delineation and just getting the general area. Anyone not doing this with fiducials? I have really good therapists and find that we’re almost always able to get the prostate aligned. It’s the SVs that are more the problem.

 

[OTN]

I don't feel like we need fiducials, so we usually don't use them. For high risk PCa I do FLAME and do use SpaceOAR, but no fiducials.

For intermediate- or low-risk PCa, I lay out allllllll the fractionation schedules available and talk about how giving more dose per treatment does indeed increase urinary toxicity. Most patients choose SBRT despite knowing the data.

Recent data showed PSMA PET might be better than MRI for boost target delineation, so I may switch to that.

 

[drowsy12]

When offered all options from brachy to sbrt to conventional, many patients will choose sbrt

 

[MidwestRadOnc]

I don't feel like we need fiducials, so we usually don't use them. For high risk PCa I do FLAME and do use SpaceOAR, but no fiducials.

For intermediate- or low-risk PCa, I lay out allllllll the fractionation schedules available and talk about how giving more dose per treatment does indeed increase urinary toxicity. Most patients choose SBRT despite knowing the data.

Recent data showed PSMA PET might be better than MRI for boost target delineation, so I may switch to that.

Do you use fiducials for SBRT? If no, re-conebeam halfway through? I was originally taught they were necessary for intrafraction motion tracking and used to use them with kV imaging during treatment. But now I'm encountering roadblocks to getting them placed or doing it myself now.

I agree with spaceOAR for boosting posterior PZ lesions. This is why I use a more modest boost. It's not uncommon to see images at the end of the day where the rectum was fuller and boost volume was overlapping anterior rectal wall. I use a 3mm PTV but crop 3mm off rectum and still it creeps in. 0mm PTV even with fiducials doesn't make any sense. It's a mobile target.

 

[OTN]

Do you use fiducials for SBRT? If no, re-conebeam halfway through? I was originally taught they were necessary for intrafraction motion tracking and used to use them with kV imaging during treatment. But now I'm encountering roadblocks to getting them placed or doing it myself now.

I agree with spaceOAR for boosting posterior PZ lesions. This is why I use a more modest boost. It's not uncommon to see images at the end of the day where the rectum was fuller and boost volume was overlapping anterior rectal wall. I use a 3mm PTV but crop 3mm off rectum and still it creeps in. 0mm PTV even with fiducials doesn't make any sense. It's a mobile target.

Re-conebeam halfway through. 3mm CTV to PTV margin. 0 mm PTV margin is fundamentally incorrect, I agree.