Thoughts on 15 year Ascende-RT data?

[DoctwoB]

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https://ascopubs.org/doi/10.1200/JCO.2026.44.7_suppl.306

People have argued against Ascende data on basis of showing a BCR benefit without a survival benefit.

Now at 15 years (with limitations based on data, death attribution, etc), combined therapy is showing a near 50% reduction in PCSM. OS 5% better in combined arm, but not significant. I'd argue showing an OS benefit is near impossible unless the effect size was absolutely massive.

Quick back of the envelope calculation shows to prove significance with a 5% OS benefit with these levels of overall mortality, you'd need around 5,000 deaths and thus a population size of about 12,000.

The final conclusion "Thus, although prostate cancer was the single most common cause of mortality in ASCENDE-RT, our results suggest that even large improvements in b-NED, such as those demonstrated with PB in ASCENDE-RT, are unlikely to improve 15-year overall survival by more than 10% for a population whose median age, performance status, and prognostic variables are similar to ASCENDE-RT participants."

While the statement is true, it also seems written in such a way as to understate the potential benefits. This is talking about the treatment of localized prostate cancer. To say something isnt a big deal since it doesn't meet a 10% OS benefit is ridiculous. Treatment of prostate cancer likely has less then a 10% OS benefit in non high risk disease.

interested to hear the thoughts of the quorum.

 

[OTN]

I have been just as impressed with the 5-year biochemical recurrence-free survival FLAME data as I was with the 5-year ASCENDE-RT data, and it does not come at the cost of significantly increased toxicity.

While I realize cross-trial comparison is not ideal, I've moved to FLAME for my high-risk patients and have been happy with the results.

 

[Aphtalyfe]

I agree with your analysis. I'd only add that the toxicity was higher in the brachy boost arm... but they were doing LDR boost.
The paper seems to be written with bias against brachytherapy... but if you show me these curves and ask me which treatment I want for my patients, myself, or my family members...

 

[WildRivers]

Agree with @OTN . I think FLAME style micro boost is criminally underused. Our practice is brachy heavy and preference is for HDR boost. But, many people don’t want that. I have been getting spacers for FLAME patients - it is really hard to meet 77 Gy < 1cc to rectum.

 

[SneakyBooger]

2017 ASCENDE Toxicity report: Redirecting
EBRT/PSI improved PFS, No OS benefit
G3+ GU toxicity 18.4% vs 5.2% with EBRT alone
Gr3+ GI toxicity 8.1% vs 3.2% (NS)
2 pts SEVERE toxicity - 1 with ischemic colitis requiring subtotal colectomy, another died from complications of fistula 8 yrs after treatment
Not stated in the 2017 pub referenced above were 2 treatment related deaths in the LDR-PB arm, none in the DE-EBRT arm. (Redirecting)
My take: LDR-PB = too toxic for a cancer that is unlikely to kill me. I choose standard conventionally fractionated EBRT for me.

 

[ramsesthenice]

Agree with @OTN . I think FLAME style micro boost is criminally underused. Our practice is brachy heavy and preference is for HDR boost. But, many people don’t want that. I have been getting spacers for FLAME patients - it is really hard to meet 77 Gy < 1cc to rectum.

100% agree. I do some kind of boost to almost everyone. The FLAME data is excellent and prospective trials looking at microboosting for SBRT are equally promising. HDR boost trials (pre-ASCEND) didn't see the added GI/GU toxicities and neither do I in my practice. I think LDR done well probably isn't as bad as ASCEND and a major issue I had with the study was it mandated the needle template. If we did an EBRT study and said every patient had to have the same beam arrangement, weighting, and field sizes, what do you think you would find?

My general preference for patients with high volume disease, minimal LUTS, and favorable anatomy is an HDR boost. If they have a discrete DIL or are not a good HDR candidate for any other reason, I like microboosting. The data isn't as mature as for ASCEND but the 5 year outcomes are excellent and tracking as well in an even more modern cohort of patients. I don't personally think HDR is more effective than a good microboost. I agree, I typically do place a spacer when doing most microboosts. I also cath them at sim to make damn sure I know where the urethra is and I typically do an MRI sim since fusing pre-spacer images to define a DIL is usually futile. I realize that is a luxury that not everyone has.

I do think the data shows boosting probably only provides meaningful clinical benefit after 5-10 years (or more) so I typically don't do any boost in patients over 75-80 unless they are robust.

 

[medgator]

2017 ASCENDE Toxicity report: Redirecting
EBRT/PSI improved PFS, No OS benefit
G3+ GU toxicity 18.4% vs 5.2% with EBRT alone
Gr3+ GI toxicity 8.1% vs 3.2% (NS)
2 pts SEVERE toxicity - 1 with ischemic colitis requiring subtotal colectomy, another died from complications of fistula 8 yrs after treatment
Not stated in the 2017 pub referenced above were 2 treatment related deaths in the LDR-PB arm, none in the DE-EBRT arm. (Redirecting)
My take: LDR-PB = too toxic for a cancer that is unlikely to kill me. I choose standard conventionally fractionated EBRT for me.

Some data out there showing brachy best for potency

But I agree. Conventional or mild hypofx for me as well with fiducials and no spacer

 

[evilbooyaa]

The trial is underpowered. Randomizing 200 patients per arm is not going to get you a statistically significant DMFS or OS benefit in localized prostate cancer. Ever. Of course they should be applauded for at least running the damn thing and giving some evidence base.

One relevant line (IMO) from the abstract: "The cumulative incidence of prostate death at 15 years was 8.6% (95%CI 5.2 – 13.0) for PB and 16.4% (95%CI 11.6 – 22.0) for EBRT (p=0.007)"

I think that's the line from this most recent abstract that is worth discussing with patients. We can't control their non-prostate cancer mortality. OS was not statistically significant so the 5% absolute change isn't something I would mention to patients.

Of course the 1-year of ADT in the DE_EBRT patients may be suboptimal compared to say 18-24 months.

LDR Boost is not worth the toxicity in 2026. LDR is fine for monotherapy but I can't see a reason to do it for a boost, if you can do HDR instead.

HDR boost has shown to have lower toxicity than LDR boost and should be the preferred means of doing brachy boost in 2026.

Those who are believers HDR boost will continue to recommend it. Those who are non-believers will feel justified to continue just doing FLAME-style boost. Follow the money as always.

There is no comparison of HDR boost vs FLAME boost.

The goal should be to do some sort of boost based on available data. I think HDR boost should see a bump given there is SOME end point beyond just bPFS that is improved with brachy boost.

Side note - for thsoe of you FLAME-style boosting - the goal was to have the treatmetn be isotoxic. If 50% of your GTV is covered to your 'boost' dose, you are helping the patient. I do not push for spacers in my FLAME patients.

 

[communitydoc13]

One relevant line (IMO) from the abstract: "The cumulative incidence of prostate death at 15 years was 8.6% (95%CI 5.2 – 13.0) for PB and 16.4% (95%CI 11.6 – 22.0) for EBRT (p=0.007)"

It's the softest endpoint. It is literally defined as death after initiation of systemic therapy for pCa. It is very likely that most of these patients did not in fact die of pCa. (We know that there is not a strong correlation between biochemical failure and mortality).

Supporting this point is the fact that distant metastatic progression was the same for both arms at 10 years.

Likely a wash regarding survival, but avoiding ADT salvage therapy not a bad thing either.

For me, FLAME style boost for high risk or unfavorable intermediate risk when target lesion identifiable and not adjacent to rectum or urethra (and urethra well delineated).

 

[WanderingRad3]

Between updated ASCENDE-RT and the TRIP trial (modern LDR brachy techniques, much lower toxicity, and potential for less ADT - https://www.redjournal.org/article/S0360-3016(23)07843-4/abstract), I have been recommending brachy + EBRT + 6-12 mo ADT (unless very high risk) fairly routinely to my high risk patients.

I do FLAME style boost for those I do not want to do brachy for (very large prostate size with high IPSS or do not want to put under anesthesia) but those patients are in the minority

 

[DoctwoB]

We frequently do LDR boost for many patients at my center, and anecdotally see very little in way of increased toxicity between monotherapy, brachy boost, and EBRT monotherapy. We are an extremely high volume ldr center, however.

Anecdotally, see a lot of patients with bad effects from HDR. Selection bias certainly likely in play, but two academic centers near me tend to dabble in HDR and i suspect aren't doing enough to really do a great job. Likewise, where I trained was a very low volume brachy center and saw poor outcomes from both LDR and HDR. I suspect it has much more to do with the operator skill and program volume then HDR vs. LDR

 

[Palex80]

 

[TheWallnerus]

View attachment 416464

American Alexander Graham Bell invented brachy (and some other stuff). So we are keepin’ it alive.
MBGA

 

[ramsesthenice]

We frequently do LDR boost for many patients at my center, and anecdotally see very little in way of increased toxicity between monotherapy, brachy boost, and EBRT monotherapy. We are an extremely high volume ldr center, however.

Anecdotally, see a lot of patients with bad effects from HDR. Selection bias certainly likely in play, but two academic centers near me tend to dabble in HDR and i suspect aren't doing enough to really do a great job. Likewise, where I trained was a very low volume brachy center and saw poor outcomes from both LDR and HDR. I suspect it has much more to do with the operator skill and program volume then HDR vs. LDR

100%. Volume matters. Both can be done very well and both can be done poorly. I am partial to HDR because it gives me a little bit better control over the final dose distribution but admittedly it is unlikely this translates into anything meaningful for most people when given a good LDR implant. Additionally, it is almost impossible to run an exceptionally high volume program using HDR. We do 4-5 implants per week which is about the most we can do with my GYN volume. We could probably triple that number no problem with LDR but we don't have the volume for it so its a non-issue.

 

[JustAdocInBox]

We frequently do LDR boost for many patients at my center, and anecdotally see very little in way of increased toxicity between monotherapy, brachy boost, and EBRT monotherapy. We are an extremely high volume ldr center, however.

Anecdotally, see a lot of patients with bad effects from HDR. Selection bias certainly likely in play, but two academic centers near me tend to dabble in HDR and i suspect aren't doing enough to really do a great job. Likewise, where I trained was a very low volume brachy center and saw poor outcomes from both LDR and HDR. I suspect it has much more to do with the operator skill and program volume then HDR vs. LDR

We have a high volume brachy practice as well. For many years we were exclusively LDR and now we do both LDR and HDR. In my experience patients treated with brachy boost have more long term toxicity GU and to some extent GI when compared to external beam alone. I see higher rates of incontinence and stricture with brachy boost patients. I've had a few patients with lingering GI issues, mainly incontinence. I have mostly switched to FLAME style boost and reserve brachy boost for younger patients with high volume high risk disease.

 

[Aphtalyfe]

We have a high volume brachy practice as well. For many years we were exclusively LDR and now we do both LDR and HDR. In my experience patients treated with brachy boost have more long term toxicity GU and to some extent GI when compared to external beam alone. I see higher rates of incontinence and stricture with brachy boost patients. I've had a few patients with lingering GI issues, mainly incontinence. I have mostly switched to FLAME style boost and reserve brachy boost for younger patients with high volume high risk disease.

Is your toxicity rate the same for LDR and HDR boost?

 

[CaesarRO]

We have a high volume brachy practice as well. For many years we were exclusively LDR and now we do both LDR and HDR. In my experience patients treated with brachy boost have more long term toxicity GU and to some extent GI when compared to external beam alone. I see higher rates of incontinence and stricture with brachy boost patients. I've had a few patients with lingering GI issues, mainly incontinence. I have mostly switched to FLAME style boost and reserve brachy boost for younger patients with high volume high risk disease.

Is your toxicity rate the same for LDR and HDR boost?

Very curious about this too

 

[evilbooyaa]

100%. Volume matters. Both can be done very well and both can be done poorly. I am partial to HDR because it gives me a little bit better control over the final dose distribution but admittedly it is unlikely this translates into anything meaningful for most people when given a good LDR implant. Additionally, it is almost impossible to run an exceptionally high volume program using HDR. We do 4-5 implants per week which is about the most we can do with my GYN volume. We could probably triple that number no problem with LDR but we don't have the volume for it so its a non-issue.

I would say doing consistently 4-5 implants a week is quite high volume for HDR prostate, my dude/dudette.

I think HDR boost is the way forward for the subset of patients who elect to undergo it (there is no clinical scenario where brachy boost is 'mandatory').

There is a learning curve but it is more forgiving than doing LDR once in a blue moon. I do think it is something worth discussing, and I think to those saying 'FLAME is enough' I would argue it's not. I would recommend that patients be offered both FLAME vs brachy boost and make the decision themselves rather than a paternalistic pathway, especially for the places that only offer FLAME boosts....

 

[ramsesthenice]

I would say doing consistently 4-5 implants a week is quite high volume for HDR prostate, my dude/dudette.

I think HDR boost is the way forward for the subset of patients who elect to undergo it (there is no clinical scenario where brachy boost is 'mandatory').

There is a learning curve but it is more forgiving than doing LDR once in a blue moon. I do think it is something worth discussing, and I think to those saying 'FLAME is enough' I would argue it's not. I would recommend that patients be offered both FLAME vs brachy boost and make the decision themselves rather than a paternalistic pathway, especially for the places that only offer FLAME boosts....

Its all relative and I agree, doing 4-5 implants a week is a decently high volume. But there are placed out there that are prostate brachy factories and will crank through 10 or so in a day. Logistically, that only works if you are doing preplanned LDR. There is no way to do that volume with HDR (or real time LDR).

 

[DoctwoB]

Its all relative and I agree, doing 4-5 implants a week is a decently high volume. But there are placed out there that are prostate brachy factories and will crank through 10 or so in a day. Logistically, that only works if you are doing preplanned LDR. There is no way to do that volume with HDR (or real time LDR).

Depends on the OR setup and docs involved. Last month we did 9 real-time LDRs and were done at lunch. Where i trained you were lucky to get two done in that time.

 

[WildRivers]

It's interesting hearing LDR vs HDR debates, as very few people do both. They both swear that their treatment is the best for X, Y, Z reasons. Such little data out there to take any sort of full-throated stance that one is better than the other. The sheer efficiency of stranded LDR is amazing. I wonder if there will ever be a real comparison. Crook study for boosts showed no difference. And I think there was some other trial where the monotherapy HDR was 19/1 and it sucked compared to LDR as far as cancer control. I'd bet cancer control same and maybe less urinary toxicity with HDR. I don't buy the Grills paper saying the potency is so much better. That doesn't really make much sense. It was HDR heavy where I work until the Californians rolled into town. It isn't that the LDR itself is the problem, it's that their selection and post-tx management is not great. Plus, they saddle the local docs with the EBRT if they need it. We've decided we will turn those patients down unless we are involved pre-treatment.

 

[ramsesthenice]

Depends on the OR setup and docs involved. Last month we did 9 real-time LDRs and were done at lunch. Where i trained you were lucky to get two done in that time.

That is impressive and honestly says more about your physics support. Someone is a machine loading the catheters!

 

[CaesarRO]

It's interesting hearing LDR vs HDR debates, as very few people do both. They both swear that their treatment is the best for X, Y, Z reasons. Such little data out there to take any sort of full-throated stance that one is better than the other. The sheer efficiency of stranded LDR is amazing. I wonder if there will ever be a real comparison. Crook study for boosts showed no difference. And I think there was some other trial where the monotherapy HDR was 19/1 and it sucked compared to LDR as far as cancer control. I'd bet cancer control same and maybe less urinary toxicity with HDR. I don't buy the Grills paper saying the potency is so much better. That doesn't really make much sense. It was HDR heavy where I work until the Californians rolled into town. It isn't that the LDR itself is the problem, it's that their selection and post-tx management is not great. Plus, they saddle the local docs with the EBRT if they need it. We've decided we will turn those patients down unless we are involved pre-treatment.

High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds - PubMed

While HDR (192 iridium) and LDR (103Pd) monotherapy maintained the same biochemical control, the use of HDR brachytherapy as monotherapy was associated with decreased rates of acute urinary frequency, urgency, dysuria and rectal pain compared to LDR. Chronic urinary frequency, urgency and grade...

pubmed.ncbi.nlm.nih.gov

Oldy but a goody

Any other direct comparative data out there?

 

[WildRivers]

High dose rate brachytherapy as prostate cancer monotherapy reduces toxicity compared to low dose rate palladium seeds - PubMed

While HDR (192 iridium) and LDR (103Pd) monotherapy maintained the same biochemical control, the use of HDR brachytherapy as monotherapy was associated with decreased rates of acute urinary frequency, urgency, dysuria and rectal pain compared to LDR. Chronic urinary frequency, urgency and grade...

pubmed.ncbi.nlm.nih.gov

Oldy but a goody

Any other direct comparative data out there?

Yah, this is the Grills paper. She works down the street from us 🙂 Alvaro Martinez is my partner.

There are a few other comparative, I mentioned above, but they aren't anything to hang hat on

Crook boost LDR vs HDR - A Randomized Comparison of High-Dose-Rate and Low-Dose-Rate Prostate Brachytherapy Combined With External Beam Radiation Therapy for Unfavorable Prostate Cancer: Efficacy Results After Median Follow-up of 74 Months - PubMed

Single fx HDR vs LDR - https://www.sciencedirect.com/science/article/abs/pii/S0167814025046286

The rest of the datasets aren't large or that enlightening

 

[evilbooyaa]

Its all relative and I agree, doing 4-5 implants a week is a decently high volume. But there are placed out there that are prostate brachy factories and will crank through 10 or so in a day. Logistically, that only works if you are doing preplanned LDR. There is no way to do that volume with HDR (or real time LDR).

I don't know that I will do 10 prostate LDRs in my life, let alone in a single day.....

 

[ramsesthenice]

I don't know that I will do 10 prostate LDRs in my life, let alone in a single day.....

I do multiple implants a week and can’t personally fathom doing 10 in a day. But I’ve done site visits to super high volume centers and like DoctwoB said, it comes down to your set up. I can physically drop 14-18 needles in someone in 5-10 minutes. If I had a suite with a couple of rooms and a super experienced physics/nursing team that essentially set up an assembly line, it’s definitely possible.

 

[CaesarRO]

Yah, this is the Grills paper. She works down the street from us 🙂 Alvaro Martinez is my partner.

There are a few other comparative, I mentioned above, but they aren't anything to hang hat on

Crook boost LDR vs HDR - A Randomized Comparison of High-Dose-Rate and Low-Dose-Rate Prostate Brachytherapy Combined With External Beam Radiation Therapy for Unfavorable Prostate Cancer: Efficacy Results After Median Follow-up of 74 Months - PubMed

Single fx HDR vs LDR - https://www.sciencedirect.com/science/article/abs/pii/S0167814025046286

The rest of the datasets aren't large or that enlightening

Interesting, thanks. Your partner's paper shows HDR has less toxicity. The single fraction paper shows HDR has more grade 1 but less grade 2 and 3 toxicity and the Crook paper, which is unique among the three in including external beam with the brachy boost, showed no difference in toxicity. You pointed at the outcomes paper but they reference their toxicity paper, which was reported earlier l

 

[medgator]

I do multiple implants a week and can’t personally fathom doing 10 in a day. But I’ve done site visits to super high volume centers and like DoctwoB said, it comes down to your set up. I can physically drop 14-18 needles in someone in 5-10 minutes. If I had a suite with a couple of rooms and a super experienced physics/nursing team that essentially set up an assembly line, it’s definitely possible.

Sadly, the only way prostate brachy makes any financial sense, esp if you are MPFS/PP IMO. They pro fees vs just being in clinic and seeing patients and treating everyone with beam is just such a wide disparity when you consider the time away in a hospital or ASC to do those procedures. If ROCR ever actually did come to pass, the way brachy is treated would be a positive.

 

[ramsesthenice]

Sadly, the only way prostate brachy makes any financial sense, esp if you are MPFS/PP IMO. They pro fees vs just being in clinic and seeing patients and treating everyone with beam is just such a wide disparity when you consider the time away in a hospital or ASC to do those procedures. If ROCR ever actually did come to pass, the way brachy is treated would be a positive.

That actually depends on your local PA and set up. In our area, we are essentially capped at 28 fractions for prostate for anyone using Evicore for PA. Doing 25 fx plus and HDR boost comes out a bit ahead of just doing 28 fx of IMRT financially. Combine that with having a Brachy suite with anesthesia in the clinic, I can schedule implants to start at 8:00 and 12:00 and squeeze in consults at 10:00 and 2:00 along with a couple of SBRTs and MRL cases. Totally agree if I had 2 days per week where implants were all I was doing it would be a very different calculation.

I personally do as much monotherapy as boosting. With HDR it’s 2 fraction which being 2 plans closes the gap a bit but still comes in behind what you pull for 28fx. However, for the right patients, it’s a great treatment and I’m happy to do it. Additionally, I’m in the NE and several of the big urology groups are pushing focal therapies (even from the NCI CCC Ivory Towers). They swear they “clearly” explain its not a curative therapy during the consent process but I treat many of their contra lateral failures and it’s very unlikely that every one of the patients is unclear on that point. Sadly, being able to offer a 2 fx therapy becomes a bit of a survival strategy in this environment.

 

[WildRivers]

Interesting, thanks. Your partner's paper shows HDR has less toxicity. The single fraction paper shows HDR has more grade 1 but less grade 2 and 3 toxicity and the Crook paper, which is unique among the three in including external beam with the brachy boost, showed no difference in toxicity. You pointed at the outcomes paper but they reference their toxicity paper, which was reported earlier l

Looks like rest of post is cut off - but I'm presuming you're going to say the balance of the published comparative data favors HDR. That may be true, but my point was that the data itself isn't very good. One small RCT comparing boosts with brachy with about 100 patients per arm, another small RCT with 50 patients in each arm but HDR arm was substandard in terms of cancer control and a non-randomized trial from a cancer center that is "all in" on HDR. HDR might be a bit less toxic, but my point is that the people that have the strongest opinions about it do either LDR or HDR and feel like the other procedure is absolutely terrible.

Brachy people always say that volume is very important. These are small trials and HDR is more forgiving. If one looks at the Merrick data or the Chicago Prostate / Moran data or Zelefsky's data for LDR, the toxicity is quite low. One of my old partners was pretty high volume LDR for a while and patients did very well with intra-op planning.

LDR or HDR or microboost - we should be boosting more patients. I'd hazard that the majority of high risk patients treated in US do not get a boost of any kind.

 

[ramsesthenice]

but my point is that the people that have the strongest opinions about it do either LDR or HDR and feel like the other procedure is absolutely terrible.

Welcome to rad onc my friend. We say breast is the worstest, but it could easily be prostate.

I’ve done a lot of both and know the literature very well. There is no high level evidence comparing the two so you can forget about making a compelling argument using published studies. My experience tells me a few things. The dosinetry will always look better with HDR which should surprise no one. You re optimize the plan after the needles are in to account for differences in where the needles actually ended up vs where you intended them to go. You also don’t have to worry about seed migration. It’s not unquestionable that you have more control over dose distribution with HDR. What does that mean for most patients? Probably not much. As you pointed out, if you do good LDR, the toxicity is low and efficacy is very high. You are hard pressed to show clinically meaningful differences in most patients. In a way, this starts to feel like protons. Dosimetric gains with no clinical correlate might make the user feel better, but patient outcomes are the end product we should care the most about.

Now, I do believe that there are times HDR has real advantages. The most notable are when patients have very big or small glands. If it’s big and you have some arch interference, you can ramp up the peripheral dwell times and push dose much further than you can with LDR. If the gland is small, you can do what I call super peripheral loading and use dwell positions that are outside of the gland to get coverage and bring down urethral dosing. Same for the (uncommon) men with a meandering urethra which deviates from R to L and really constrains your anterior needle positioning. I think the literature does suggest slightly better toxicity outcomes with HDR but it’s probably 90% driven by specific subsets like these.

They are both good treatments and largely equivalent most of the time IMO.