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