Moderate hypo? Meh. Ultrahypo is the future

[Chartreuse Wombat]

---

Members do not see this ad.

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31131-6/fulltext

Strange that it is not open access.

 

[medgator]

Until CMS starts allowing for 7 fx SBRT, I don't see this taking off in the US at all, nevermind the increased toxicity issues

 

[evilbooyaa]

Increased rates of acute GU toxicity and GU toxicity at one year.

Here we go again. I look forward to the same arguments as in the prostate hypofrac thread(s). I imagine people will tell us to ignore increased acute toxicity (as was done with moderate hypofrac) in the interest of shortening treatment schedules. Can be offered to patients if you want to bill 7fx IMRT.

All people wanna do is justify treating with less fractions. European trials focused on cost-cutting will do this despite increases in toxicity, and scream that fee-for-service is the enemy of the patient.

If it's me I want the treatment that will give me the least toxicity in all phases with the best outcome, duration of treatment be damned.

Why don't we work on increasing that 84% bPFS at 5 years number? Why is that not the focus, rather than inducing more toxicity to get patients done in the interest of patient convenience?

 

[deleted941485]

Increased rates of acute GU toxicity and GU toxicity at one year.

Here we go again. I look forward to the same arguments as in the prostate hypofrac thread(s). I imagine people will tell us to ignore increased acute toxicity (as was done with moderate hypofrac) in the interest of shortening treatment schedules. Can be offered to patients if you want to bill 7fx IMRT.

All people wanna do is justify treating with less fractions. European trials focused on cost-cutting will do this despite increases in toxicity, and scream that fee-for-service is the enemy of the patient.

If it's me I want the treatment that will give me the least toxicity in all phases with the best outcome, duration of treatment be damned.

Why don't we work on increasing that 84% bPFS at 5 years number? Why is that not the focus, rather than inducing more toxicity to get patients done in the interest of patient convenience?

I feel like as time goes by the hypofrac crowd just keeps getting more and more radical. Ignoring toxicities and using non-inferiority studies over and over again.

 

[deleted941485]

Increased rates of acute GU toxicity and GU toxicity at one year.

Here we go again. I look forward to the same arguments as in the prostate hypofrac thread(s). I imagine people will tell us to ignore increased acute toxicity (as was done with moderate hypofrac) in the interest of shortening treatment schedules. Can be offered to patients if you want to bill 7fx IMRT.

All people wanna do is justify treating with less fractions. European trials focused on cost-cutting will do this despite increases in toxicity, and scream that fee-for-service is the enemy of the patient.

If it's me I want the treatment that will give me the least toxicity in all phases with the best outcome, duration of treatment be damned.

Why don't we work on increasing that 84% bPFS at 5 years number? Why is that not the focus, rather than inducing more toxicity to get patients done in the interest of patient convenience?

When single payer hits the US, we will also be convieniantly ignoring this as well. Naysayers will be silenced accordingly.

 

[medgator]

When single payer hits the US, we will also be convieniantly ignoring this as well. Naysayers will be silenced accordingly.

Depends on which practice you're at.... The govt one or your private one 😉

Canada's Private Clinics Surge as Public System Falters (Published 2006)

The Cambie Surgery Center, Canada's most prominent private hospital, may be considered a rogue enterprise. Accepting money from patients for operations they would otherwise receive free of charge in a public hospital is technically prohibited in this country, even in cases where patients...

www.nytimes.com

Even in the UK, private practices still exist

 

[mavrik13]

I'm sorry, but give me a break - acute urinary toxicity was 6% vs 2% at 1 year. You would need to treat 25 people with conventional fractionation to save a single person from acute toxicity at a single time point. Care to do the math on the cost to save that single toxicity outcome, which ironically balances out in the long-term? We also know once-weekly fractionation decreases acute GU/GI toxicity in 5 fraction SBRT, instead of accelerating the treatment as well.

We aren't rad oncs from the 1980's anymore using conventional sims and treating large areas unnecessarily, and choosing our doses by toxicity. It's ok to move away from 1.8-2 Gy per day, and we now have level 1 evidence to support ultrahypofractionation.

 

[Palex80]

Results look promising, but I would like to see some more mature follow up and confirmation trials. But yes, it is highly like that this may become standard of care in the years to come.

And look what's coming...

ONE SHOT - single shot radiotherapy for localized prostate cancer: study protocol of a single arm, multicenter phase I/II trial - Radiation Oncology

Background Stereotactic body radiotherapy (SBRT) is an emerging treatment alternative for patients with localized prostate cancer. Promising results in terms of disease control and toxicity have been reported with 4 to 5 SBRT fractions. However, question of how far can the number of fractions...

ro-journal.biomedcentral.com

 

[evilbooyaa]

I'm sorry, but give me a break - acute urinary toxicity was 6% vs 2% at 1 year. You would need to treat 25 people with conventional fractionation to save a single person from acute toxicity at a single time point. Care to do the math on the cost to save that single toxicity outcome, which ironically balances out in the long-term? We also know once-weekly fractionation decreases acute GU/GI toxicity in 5 fraction SBRT, instead of accelerating the treatment as well.

We aren't rad oncs from the 1980's anymore using conventional sims and treating large areas unnecessarily, and choosing our doses by toxicity. It's ok to move away from 1.8-2 Gy per day, and we now have level 1 evidence to support ultrahypofractionation.

Called it.

Why is Radiation Oncology the only specialty that has to self-regulate on cost? Why are we the only specialty to insist on self-flagellation to recommend to our patients a more toxic treatment in the interest of cost savings?

Surgery doesn't do this. Med-onc doesn't do this.

I will continue pushing for the LEAST toxic treatment for my patients regardless of reimbursement schedule. I will certainly offer it to patients if they want to get done super quickly. This is why I am a believer in breast hypofrac (I wouldn't even really offer standard breast for WBI alone anymore) and not a mandatory adopter of prostate hypofrac.

But I look forward to people telling me I am just another money-grubbing Rad Onc.

Those pushing for ultra-hypofrac - what would you want as a patient? Do you discuss the increase in toxicity seen with your recommendation?

 

[medgator]

This is why I am a believer in breast hypofrac (I wouldn't even really offer standard breast for WBI alone anymore) and not a mandatory adopter of prostate hypofrac.

But I look forward to people telling me I am just another money-grubbing Rad Onc.

Those pushing for ultra-hypofrac - what would you want as a patient? Do you discuss the increase in toxicity seen with your recommendation?

Nailed it. Breast outcomes, according to some data, are actually better with hypofx.

Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial - PubMed

clinicaltrials.gov Identifier: NCT01266642.

www.ncbi.nlm.nih.gov

Not analogous to prostate hypofx at all

 

[Chartreuse Wombat]

Called it.

Why is Radiation Oncology the only specialty that has to self-regulate on cost? Why are we the only specialty to insist on self-flagellation to recommend to our patients a more toxic treatment in the interest of cost savings?

Surgery doesn't do this. Med-onc doesn't do this.

I will continue pushing for the LEAST toxic treatment for my patients regardless of reimbursement schedule. I will certainly offer it to patients if they want to get done super quickly. This is why I am a believer in breast hypofrac (I wouldn't even really offer standard breast for WBI alone anymore) and not a mandatory adopter of prostate hypofrac.

But I look forward to people telling me I am just another money-grubbing Rad Onc.

Those pushing for ultra-hypofrac - what would you want as a patient? Do you discuss the increase in toxicity seen with your recommendation?

The least toxic? Care to tell me what your dose is for typical conventional fractionation prostate? You know that 79.2 Gy is more toxic than 70.2 with no difference in OS.

 

[xrthopeful]

what would you want as a patient?

Easy. To not have to come for 9 weeks. During training especially, cost has nothing to do with it, but I did love to be able to tell a patient they only had to come for 28 or 20 treatments or for those who elected it - only 5.

 

[medgator]

Easy. To not have to come for 9 weeks. During training especially, cost has nothing to do with it, but I did love to be able to tell a patient they only had to come for 28 or 20 treatments or for those who elected it - only 5.

My retired patients hate waking up more at night than the 2-3x they are already than coming in for more fractions. They'd really hate having to get a Foley catheter even more.

I've done 28 fx hypofx a few times for the pts I've had that worked through tx. They definitely noticed the GU effects more but were fine with their decision

 

[xrthopeful]

Agree that the 28 fx folks are peeing a bit more often, but most do seem fine with it. It’s all about setting expectations I suppose. I haven’t seen any require a foley tho. They brachy patients yeah some require one.

 

[Chartreuse Wombat]

My retired patients hate waking up more at night than the 2-3x they are already than coming in for more fractions. They'd really hate having to get a Foley catheter even more.

I've done 28 fx hypofx a few times for the pts I've had that worked through tx. They definitely noticed the GU effects more but were fine with their decision

Foley catheter...hmmm what is the published rate of urinary retention with external beam?

 

[medgator]

Foley catheter...hmmm what is the published rate of urinary retention with external beam?

I actually saw it happen once....

Was a tongue in cheek comment, but to be sure, I've had patients coming in with double digit aua scores who had no problem coming in for 8-9 weeks

 

[evilbooyaa]

The least toxic? Care to tell me what your dose is for typical conventional fractionation prostate? You know that 79.2 Gy is more toxic than 70.2 with no difference in OS.

Yes, but there are improvements in bPFS with 79.2 compared to 70.2! Is this a serious statement? We, as oncologists, accept higher toxicity rates when we are curing more people. You are advocating for increasing toxicity rates with the only benefit to the patients being less treatments.

Listen, if you told me that a 5 or 10 fraction regimen had improved bPFS but higher rates of toxicity I'd be all about it. That's what the initial hypofractionation trials were supposed to show anyways. Then the push became cost, cost, and convenience at the expense of patient toxicities.

Again, if YOU want to do offer or recommend it to your patients then fine, do your thing. To each their own.

I look forward to the 'bPFS isn't a worthwhile endpoint in prostate cancer' argument.

 

[Lamount]

I look forward to the 'bPFS isn't a worthwhile endpoint in prostate cancer' argument.

Then allow me to oblige...

People suffer from toxicities;
People suffer from the crushing debt of treatment;
People do not suffer from bad lab results unless they become something more.

All things being equal, I obviously prefer a treatment that offer better bPFS. But if all things are not equal, then it is hard for me to formally recommend intensification unless a patient decides to prioritize an intangible endpoint over tangible toxicities and costs.

 

[Chartreuse Wombat]

Yes, but there are improvements in bPFS with 79.2 compared to 70.2! Is this a serious statement? We, as oncologists, accept higher toxicity rates when we are curing more people. You are advocating for increasing toxicity rates with the only benefit to the patients being less treatments.

Listen, if you told me that a 5 or 10 fraction regimen had improved bPFS but higher rates of toxicity I'd be all about it. That's what the initial hypofractionation trials were supposed to show anyways. Then the push became cost, cost, and convenience at the expense of patient toxicities.

Again, if YOU want to do offer or recommend it to your patients then fine, do your thing. To each their own.

I look forward to the 'bPFS isn't a worthwhile endpoint in prostate cancer' argument.

It is a serious statement. BTW you didn't answer the question I asked. From your response I am guessing that you use 79.2 Gy. The absolute difference in toxicity is 10-15% (cf. 4% as described above) with 79.2 versus 70.2.

As you predicted I will state that bPFS is not a meaningful clinical endpoint. DM or PCSM are and it is clear that 6 months of ADT can change those endpoints but 6-8 Gy can't (at least not yet). Salvage therapy is a bad endpoint since most biochemical recurrences require no treatment.

With respect to "improvements" with hypofractionation there are at least "hints" that there is more efficacy with moderate hypofractionation in the 5-10 year range. The MD Anderson trial shows this and the NRG 0415 curves are suggesting that is the case. Late local recurrences happen in the 5-10 period. Of course these studies use biochemical endpoints and are not powered for DM or PCSM and therein is the conundrum of clinical trials in non-metastatic prostate cancer.

To each their own is something most can agree with but it really adds little to the conversation. I don't pretend to know anyone's motives for the fractionation schedule that they chose to offer individual patients but let's not equate differences in a laboratory test outcomes with distant metastases or death from prostate cancer. ASCENDE-RT showed a huge difference in bRFS but none of the meaningful endpoints were different.

 

[ramsesthenice]

They definitely noticed the GU effects more but were fine with their decision

I personally have not been able to see this. I offer almost everyone 79 in 42 or 70 in 30. I always point out that a lot of very smart think it could increase the risk of long term urinary toxicity. I’d say 70% or so opt for 70 in 30. I like to think I keep good track of my patients and try very hard to figure out how they are doing. If there is a difference in long term GI or GU tox with moderate hypofractionated prostate RT it seems subtle to me. Enough people with far more experience than myself (Gator included) have seen it so I find it hard to write off. But if expectations are set properly from the beginning most parties seem to end up happy.

 

[evilbooyaa]

@Lamount and @Chartreuse Wombat

If you are not believers in bPFS as a valid endpoint in prostate cancer, then this entire discussion is going to go nowhere and is honestly not worth having. Some people focus on cure in all aspects, other people focus only on symptomatic or metastatic recurrence.

Last point I'll make - what are both of YOUR conventional fractionation doses as folks who don't believe in bPFS? Are you doing higher than 70 Gy? If so, why? I request that people who don't believe in bPFS as a valid endpoint do so consistently. Not cherry pick based on personal or institutional biases.

I don't really see the point of continuing the conversation about toxicity and hypofractionation as we are on two different sides of a fence. I believe in bPFS. I believe in maximizing utilization of things that will lead to a higher plateau of a bPFS curve (not just kick the can down the road like hormones in early/intermediate stage prostate cancer) with acceptable toxicity.

I believe in dose escalated EBRT over 70Gy (even with worse toxicity).
I believe in brachy boost per ASCENDE-RT (even with worse toxicity). BTW I look forward to ASCENDE-RT finally shutting nay-sayers up. Early results of other prostate trials initially showing just bPFS benefits eventually turned into DM/OS benefits.
I believe in considering consolidative systemic therapy in extremely high-risk patients (even with worse toxicity).

What I don't believe in is accepting a treatment with equivalent outcomes in EVERY data point with higher toxicity. Which is what is being pushed relentlessly.

The argument of "hints" of improved efficacy with hypofrac is laughable, IMO. We, as a field, can't just accept that we were wrong about rad bio modeling of 'increased' efficacy if you truly believe there are 'hints' of improved efficacy with hypofrac. Come back when there are real results on that thought process.

 

[Mandelin Rain]

Having seen plenty of guys with a rising PSA post therapy, there is definitely some harm to that lab. Anxiety, stress, depression, salvage hormones, salvage cryo, etc... etc... etc... Let's say, nothing positive comes from it.

I bet you all check PSAs post therapy. If you think it honestly doesn't matter at all, why not just order annual bone scans or something instead?

 

[medgator]

@Lamount and @Chartreuse Wombat
Early results of other prostate trials initially showing just bPFS benefits eventually turned into DM/OS benefits.

Cough *swog post-prostatectomy xrt* cough

 

[Lamount]

ok ok... let's clear a few things up.

For individual patients:
Are PSAs important in screening for prostate cancer and monitoring response to therapy? yes
If a patient develops a biochemical failure following radiation therapy, is this a significant event that could lead to additional therapies? yes
For a given individual patient, could a biochemical failure be a harbinger for additional prostate cancer associated morbidity and mortality? yes
is this always the case?...no

For patient populations:
Are there studies where differences in bPFS led to differences in metastasis-free survival or OS? yes
Can we conclude that for, for every population, under every circumstance, bPFS can be a surrogate for MFS or OS (or even correlated with MFS or OS)?... no
Even if bPFS were always correlated with MFS and OS, can we conclude that a statistically significant difference in bPFS translates to a statistically significant and/or clinically meaningful difference in MFS or OS?... no.
Thus, can we assume that bPFS is always a meaningful endpoint when evaluating the efficacy of oncologic treatments for prostate cancer?... nope
Might this change in the future?...yes, but we aren't there yet.

 

[evilbooyaa]

ok ok... let's clear a few things up.

For individual patients:
Are PSAs important in screening for prostate cancer and monitoring response to therapy? yes
If a patient develops a biochemical failure following radiation therapy, is this a significant event that could lead to additional therapies? yes
For a given individual patient, could a biochemical failure be a harbinger for additional prostate cancer associated morbidity and mortality? yes
is this always the case?...no

Do we have a robust, validated, means of differentiating these two patient populations (whether the PSA is predictive of DMFS or OS or not) from one another? No. (Happy to be educated on this topic btw, if there are nomograms or other evidence evaluating this beyond just 'PSADT matters!!')

For patient populations:
Are there studies where differences in bPFS led to differences in metastasis-free survival or OS? yes
Can we conclude that for, for every population, under every circumstance, bPFS can be a surrogate for MFS or OS (or even correlated with MFS or OS)?... no
Even if bPFS were always correlated with MFS and OS, can we conclude that a statistically significant difference in bPFS translates to a statistically significant and/or clinically meaningful difference in MFS or OS?... no.
Thus, can we assume that bPFS is always a meaningful endpoint when evaluating the efficacy of oncologic treatments for prostate cancer?... nope
Might this change in the future?...yes, but we aren't there yet.

Agree with all of the above.

Does a biochemical recurrence lead to symptomatic local or distant recurrence prior to the patient dying of other causes near 100% of the time? No
Does a biochemical recurrence lead to additional testing, treatment, and/or anxiety near 100% of the time? Yes
Does a biochemical recurrence mean that the patient is not 'cured' of their prostate cancer near 100% of the time? Yes

Similar thought process - do you consider local recurrence as a valid endpoint for breast cancer, or do you only believe in DMFS or OS?

I'll ask it again - what dose do you use for conventionally fractionated prostate radiation? Based off your arguments about the invalidity of bPFS I'm assuming you only treat these to 70Gy.

 

[xrthopeful]

The better argument is that the acute toxicity difference is quite marginal. In fact, 0415 isn’t even a fair comparison as has been discussed here prior.

 

[Chartreuse Wombat]

Do we have a robust, validated, means of differentiating these two patient populations (whether the PSA is predictive of DMFS or OS or not) from one another? No. (Happy to be educated on this topic btw, if there are nomograms or other evidence evaluating this beyond just 'PSADT matters!!')



Agree with all of the above.

Does a biochemical recurrence lead to symptomatic local or distant recurrence prior to the patient dying of other causes near 100% of the time? No
Does a biochemical recurrence lead to additional testing, treatment, and/or anxiety near 100% of the time? Yes
Does a biochemical recurrence mean that the patient is not 'cured' of their prostate cancer near 100% of the time? Yes

Similar thought process - do you consider local recurrence as a valid endpoint for breast cancer, or do you only believe in DMFS or OS?

I'll ask it again - what dose do you use for conventionally fractionated prostate radiation? Based off your arguments about the invalidity of bPFS I'm assuming you only treat these to 70Gy.

Where to begin?

I haven't used 1.8-2 Gy in >10 years (73.8 or 74 Gy back then). Default is now 70 in 28 or SBRT. On occasion will use 60 in 20 if travel is difficult.

I don't have a nomogram but there is lots of evidence that BCR recurrence has limited prostate cancer mortality in patients with low and int risk disease; frequently these patients are overtreated with "salvage ADT" that only gives them side effects. High risk disease not so much.

Another commenter suggested that ASCENDE-RT will eventually show differences in DM or PCSM. I doubt it very much primarily because the study enrolled less than 400 patients. Even in this population (70% HR and 30% IR), to date only 18 of the 68 deaths (26%) are related to prostate cancer. Competing comorbidities will drown out effects on prostate cancer mortality. If you want to show a 25% reduction in an outcome you need 150-200 events in each arm. BTW I do use brachy boost in high risk men but I hypofractionate the external beam (37.5 in 15).

BTW your statement that prostate hypo ALWAYS has more toxicity is cherry picking. The two largest studies (CHHiP n=3200) and (PROFIT n=1200) found no differences in late GU/GI toxicity or patient reported outcomes. In fact PROFIT found late GI toxicity to be slightly less with hypo.

0415 was the only study at 2.5-3Gy that showed excess late toxicity. I am speculating but i attribute this to two effects: 1) the standard arm was low dose by contemporary standards-one would expect that if the standard was 79.2 toxicity would be the same. 2) the dose constraints were very liberal given that IMRT was not widely available when the study was initially designed and there was concern that the constraints couldn't be too tight. In 2019 with daily IGRT and IMRT it is possible to meet much tighter constraints on a routine basis even with large prostates.

With regard to self-flagellation. One of the tenets of medical professionalism is to use resources wisely. Part of my practice is in a resource constrained environment. If I hypofractionate prostate then the folks with locally advanced head and neck or lung cancer can begin treatment without delay because there are fewer demands on linac time.

 

[medgator]

. One of the tenets of medical professionalism is to use resources wisely. Part of my practice is in a resource constrained environment. If I hypofractionate prostate then the folks with locally advanced head and neck or lung cancer can begin treatment without delay because there are fewer demands on linac time.

Slippery slope. Technically if I have the machine time, I shouldn't offer the patient a less toxic treatment if they are willing to come in more often?

I bet in the truly capitated environment,s (KP, VA etc) toxicity is just the unfortunate byproduct of finishing patients quicker for the available radiation "resource"

 

[evilbooyaa]

Thank you for repeating your arguments from the prostate hypofrac thread once again. Please stop attempting to put words in my mouth about late toxicities because you are unable to remember the discussion of that topic across multiple threads. My issue with prostate moderate hypofrac is primarily on rates of ACUTE GI toxicity being higher, and the hypofrac guidelines AGREE with me, with this statement in their guidelines:

Statement KQ1E: "Men should be counseled about the small increased risk of acute gastrointestinal (GI) toxicity with moderate hypofractionation."

My beef with ultrahypofrac is not only late GU toxicity at 1 year, but acute GU toxicity. We are making patients feel worse as a result of our treatment without an oncological benefit to the individual patient.

I still offer prostate hypofrac to the rare intact patient I see (usually 70/28). I discuss with them the potential for increased acute GI toxicity as a result of treatment.

And come on at your last paragraph, Aren't you in academics or something given your history with RRC? Are we calling academic departments 'resource constrained' like they're in the middle east or Africa, that we need to increase machine throughput for 'societal' good?

 

[maruchan]

I have a hard time reconciling the viewpoint that bPFS is not a "meaningful" endpoint while simultaneously saying that saving a few weeks by doing hypofractionation is "meaningful."

A biochemical failure may or may not affect overall survival, but it certainly causes significant stress, additional visits, additional consultations, likely additional therapies, and changes the way a person thinks about and lives their life. That is far more impactful than prolonging the duration of radiation, both in cost to the system and experience of the individual. If you think a biochemical failure is not meaningful, try talking to a patient.

 

[Lamount]

I have a hard time reconciling the viewpoint that bPFS is not a "meaningful" endpoint while simultaneously saying that saving a few weeks by doing hypofractionation is "meaningful."

Firstly, there are numerous trials that demonstrate non-inferiority of hypo-fract with respect to biochemical control... and the early results from extreme hypo-fact are encouraging. So you don't have to choose.

But hypothetically, just to posit a question... if there were a trial with a sample size large enough to demonstrate that there was a 1.5% improvement in biochemical control with a 9 week course of EBRT vs. a 5 day course of SBRT (NNT to prevent 1 biochemical failure = 67), would you offer SBRT, or would you keep this option from the patient because of the inferior control... or would you discuss the pros and cons of each modality. Convenience may not seem like an important factor to us... but for many patients, it entirely influences their decision to undergo treatment. Some don't have the luxury of being able to put their life on hold for treatment.

 

[xrthopeful]

For those of you who support long-course, 8 or 9 week regimens for prostate intact due to increased acute toxicity with shorter regimens- I hope you also mostly use 8/1 over 30/10 for bone met palliation.

8/1 - more convenient, less acute toxicity. Higher chance of having to come back in later for another treatment, but hey, these retired patients don't mind a 1 in 5 chance of having to come back (vs 1 in 10).

(for the record, I think 8/1 is great. I suspect some of you don't though. I wonder what the difference is here.....)

 

[maruchan]

Firstly, there are numerous trials that demonstrate non-inferiority of hypo-fract with respect to biochemical control... and the early results from extreme hypo-fact are encouraging. So you don't have to choose.

But hypothetically, just to posit a question... if there were a trial with a sample size large enough to demonstrate that there was a 1.5% improvement in biochemical control with a 9 week course of EBRT vs. a 5 day course of SBRT (NNT to prevent 1 biochemical failure = 67), would you offer SBRT, or would you keep this option from the patient because of the inferior control... or would you discuss the pros and cons of each modality. Convenience may not seem like an important factor to us... but for many patients, it entirely influences their decision to undergo treatment. Some don't have the luxury of being able to put their life on hold for treatment.

I think you completely missed the point of my post.

First of all, I'm not saying that hypofrac has worse biochemical control. I'm referring to those posters who are simultaneously advocating for hypofrac while pooh-poohing BFS as an endpoint. I'm saying those viewpoints are incongruent.

I'm not saying patient convenience is unimportant. I'm saying that the patient experience is important, but the impact on patient experience of a biochemical failure far exceeds that of a longer radiation course, so if you care about one you should definitely care about the other. To hold up hypofrac as a shining boon for patients due to the convenience while passing off a biochemical failure as just a "bad lab test" and state that "people do not suffer from bad lab tests" is nonsensical.

 

[Lamount]

I think you completely missed the point of my post.

First of all, I'm not saying that hypofrac has worse biochemical control. I'm referring to those posters who are simultaneously advocating for hypofrac while pooh-poohing BFS as an endpoint. I'm saying those viewpoints are incongruent.

I'm not saying patient convenience is unimportant. I'm saying that the patient experience is important, but the impact on patient experience of a biochemical failure far exceeds that of a longer radiation course, so if you care about one you should definitely care about the other. To hold up hypofrac as a shining boon for patients due to the convenience while passing off a biochemical failure as just a "bad lab test" and state that "people do not suffer from bad lab tests" is nonsensical.

Sorry for the misunderstanding and I agree with most of what you said. We may be speaking past each other.

If hypo-fx were biochemically inferior to standard EBRT with a clinically meaningful hazard ratio, I would be very reluctant to recommend it. But given that biochemical failure frequently occurs with a microscopic disease burden and can long proceed a symptomatic recurrence, and given that prostate cancer patients frequently have competing comorbidities, I would not consider all statistically significant differences in bPFS to be clinically meaningful. Fortunately, we are not in that situation as there are no data to suggest inferiority of hypo-fx (at least none any that I am aware of).

 

[PointA]

I find these endless fractionation debates very tiring. No one is changing anyone else's mind. If you want to treat with conventional fractionation, then go ahead. If you want to treat with hypofrac, then go ahead. Both are reasonable options. All we do in this specialty is talk about fractionation over and over again for every disease site. If I was a med student, this would turn me off the field.

 

[Chartreuse Wombat]

Thank you for repeating your arguments from the prostate hypofrac thread once again. Please stop attempting to put words in my mouth about late toxicities because you are unable to remember the discussion of that topic across multiple threads. My issue with prostate moderate hypofrac is primarily on rates of ACUTE GI toxicity being higher, and the hypofrac guidelines AGREE with me, with this statement in their guidelines:

Statement KQ1E: "Men should be counseled about the small increased risk of acute gastrointestinal (GI) toxicity with moderate hypofractionation."

My beef with ultrahypofrac is not only late GU toxicity at 1 year, but acute GU toxicity. We are making patients feel worse as a result of our treatment without an oncological benefit to the individual patient.

I still offer prostate hypofrac to the rare intact patient I see (usually 70/28). I discuss with them the potential for increased acute GI toxicity as a result of treatment.

And come on at your last paragraph, Aren't you in academics or something given your history with RRC? Are we calling academic departments 'resource constrained' like they're in the middle east or Africa, that we need to increase machine throughput for 'societal' good?

I think you are painting with a rather large brush to suggest that academic departments don't operate in resource constrained environments. There are some that can charge monopolistic rates but not all.

 

[medgator]

I think you are painting with a rather large brush to suggest that academic departments don't operate in resource constrained environments. There are some that can charge monopolistic rates but not all.

I'm guessing a big chunk, if not the majority, carry NCI designation, with the resultant special treatment from CMS in terms of reimbursement

 

[Chartreuse Wombat]

Marvelously imprecise "big chunk". I am not an expert in this particular are to be sure.

I know that there are 11 cancer centers in the US that are exempt from Medicare PPS; recent analysis at link below

Comparison of PPS-Exempt Hospitals, NCI-Designated Hospitals, and Other Hospitals That Provide Cancer Care

This cohort study compares the characteristics and postoperative outcomes of hospitals affiliated with Prospective Payment System (PPS)-exempt cancer centers, other hospitals affiliated with National Cancer Institute (NCI)-designated cancer centers, and other hospitals that provide cancer care in...

jamanetwork.com

I have not seen specifics on reimbursement for these exempt centers to know whether they are recieving more for the same service but the paper above makes clear that the regulatory burden is less.

Please enlighten me as to whether NCI designation, in and of itself, is associated with more favorable reimbursement. Serious question.

There are roughly 40 NCI designated centers and approximately 90 "academic" programs with radiation oncology residency.

 

[scarbrtj]

There’s data that 81/45 actually makes urinary problems better for some. Some men come in with high AUA scores and have urinary improvements after XRT that are equal in magnitude to that of a TURP. Perhaps this is a function that high AUA scores can only stay stable or go down over time, but still I haven’t seen a hint of this on the hypofx side, only conv fx schedules. Not saying it can’t happen and am open to the possibility. Of all the cancers I have treated in my career, I have treated prostate the most. By far. Thousands. I am as intimately acquainted with all the potentialities—good, bad, acute, late, technique, imponderables—of 81/45 as I am my own fingernails. Anything else I’ll try will be a mini-experiment I’m running on the first, second, hundredth patient I try to treat differently. This is from whence I come when I talk about prostate. Have pity on this poor, anachronistic fellow who’s been phenomenally clinically successful and happy with his prostate cancer treatments.

 

[xrthopeful]

Of all the cancers I have treated in my career, I have treated prostate the most. By far. Thousands. I am as intimately acquainted with all the potentialities—good, bad, acute, late, technique, imponderables—of 81/45 as I am my own fingernails. Anything else I’ll try will be a mini-experiment I’m running on the first, second, hundredth patient I try to treat differently. This is from whence I come when I talk about prostate. Have pity on this poor, anachronistic fellow who’s been phenomenally clinically successful and happy with his prostate cancer treatments.

I think that's a fair approach.

 

[RickyScott]

Marvelously imprecise "big chunk". I am not an expert in this particular are to be sure.

I know that there are 11 cancer centers in the US that are exempt from Medicare PPS; recent analysis at link below

Comparison of PPS-Exempt Hospitals, NCI-Designated Hospitals, and Other Hospitals That Provide Cancer Care

This cohort study compares the characteristics and postoperative outcomes of hospitals affiliated with Prospective Payment System (PPS)-exempt cancer centers, other hospitals affiliated with National Cancer Institute (NCI)-designated cancer centers, and other hospitals that provide cancer care in...

jamanetwork.com

I have not seen specifics on reimbursement for these exempt centers to know whether they are recieving more for the same service but the paper above makes clear that the regulatory burden is less.

Please enlighten me as to whether NCI designation, in and of itself, is associated with more favorable reimbursement. Serious question.

There are roughly 40 NCI designated centers and approximately 90 "academic" programs with radiation oncology residency.

The preferential reimbursement is not nearly as big an issue as the rates that these and similar centers can negotiate with insurance. NCI designation does not carry a benefit, it is the pps exemption for a select group of academic centers.

 

[scarbrtj]

For those of you who support long-course, 8 or 9 week regimens for prostate intact due to increased acute toxicity with shorter regimens- I hope you also mostly use 8/1 over 30/10 for bone met palliation.

8/1 - more convenient, less acute toxicity. Higher chance of having to come back in later for another treatment, but hey, these retired patients don't mind a 1 in 5 chance of having to come back (vs 1 in 10).

(for the record, I think 8/1 is great. I suspect some of you don't though. I wonder what the difference is here.....)

8/1 is my go to and it was easy to incorporate into practice because there was a clinical reason to use it. One, as a radiobiologist it’s easy to predict 8/1 would have less side effects than 30/10 and two, the clinical data backed that up with statistically significant side effect differences. (And the data showed it had less tumor effect; acceptable in palliation.) For prostate hypofx the data has offered no compelling clinical reason for me to change practice. On the contrary, it at times whispers worries in my ear with occasionally statistically significant side effect disimprovement. Radiobiology led us to this state in prostate. It’s predicated on uniformly low alpha/betas for CaP. If you google the recent single shot data for CaP, there are increased failures that shouldn’t happen. I think because CaP is alpha/beta heterogenous; ie biology. Incidentally high dose conventional fractionation is a wonderful hedge against low alpha/beta tumor heterogeneity.

 

[ramsesthenice]

8/1 is my go to and it was easy to incorporate into practice because there was a clinical reason to use it. One, as a radiobiologist it’s easy to predict 8/1 would have less side effects than 30/10 and two, the clinical data backed that up with statistically significant side effect differences. (And the data showed it had less tumor effect; acceptable in palliation.) For prostate hypofx the data has offered no compelling clinical reason for me to change practice. On the contrary, it at times whispers worries in my ear with occasionally statistically significant side effect disimprovement. Radiobiology led us to this state in prostate. It’s predicated on uniformly low alpha/betas for CaP. If you google the recent single shot data for CaP, there are increased failures that shouldn’t happen. I think because CaP is alpha/beta heterogenous; ie biology. Incidentally high dose conventional fractionation is a wonderful hedge against low alpha/beta tumor heterogeneity.

In the metastatic setting there is something to the alpha beta argument. I use 38/4 for prostate oligomets extrapolating from previous definitive SBRT doses. I am not sure I have ever seen an in field failure with these doses. Granted, they are almost all nodal and bone Mets which biologically seem to be easier to control across the board. But still, does anyone else use those doses for lung, breast, or colon Mets? I don’t. The only other disease I will use this for is RCC...also a low alpha/beta tumor.

But your point is valid. The extreme hypofrac regimens have vastly higher BEDs and theoretically should be better...but are not. Of course, there is a pretty good explanation. There are not that many isolated local failures after prostate RT using any fractionation. It was never realistic to expect hypofractionation (or Brachy boost for that matter) were likely to significantly change outcomes. It would be nice to be wrong on this one, but I doubt I am.

 

[Mandelin Rain]

ok ok... let's clear a few things up.

For individual patients:
Are PSAs important in screening for prostate cancer and monitoring response to therapy? yes

Why? If it stays the same, okay. If it goes down, great. If it goes up, you said it doesn't matter as an outcome.

I'd posit that if DMFS and OS are the outcomes that actually matter, you'd be best served by checking to make sure the patient is alive and ordering a bone scan periodically.

So... why are you measuring an outcome you find meaningless and has the potential to cause further harm? Unless, of course, you don't actually believe it's meaningless.

 

[scarbrtj]

In the metastatic setting there is something to the alpha beta argument. I use 38/4 for prostate oligomets extrapolating from previous definitive SBRT doses. I am not sure I have ever seen an in field failure with these doses. Granted, they are almost all nodal and bone Mets which biologically seem to be easier to control across the board. But still, does anyone else use those doses for lung, breast, or colon Mets? I don’t. The only other disease I will use this for is RCC...also a low alpha/beta tumor.

But your point is valid. The extreme hypofrac regimens have vastly higher BEDs and theoretically should be better...but are not. Of course, there is a pretty good explanation. There are not that many isolated local failures after prostate RT using any fractionation. It was never realistic to expect hypofractionation (or Brachy boost for that matter) were likely to significantly change outcomes. It would be nice to be wrong on this one, but I doubt I am.

Well you are on the right track with dose escalation for "palliative SBRT" as now, I guess, in terms of tx effectiveness for bone mets:
SBRT to 12-16 Gy better than 30 Gy/10 better than 8 Gy/1
So 38/4 should beat the crap out of all three heh.
In the 19/1 trial for prostate cancer they saw increased failures for high risk.
Let's suppose that α/β is valid at high doses, which is reasonable.

ISOEFFECTIVE 2Gy-PER FX DOSE REGIMENS AT DIFFERENT α/β's
..........................α/β=2.5...........α/β=3.5.........α/β=4.5
19Gy/1 fx........90/45.................78/39...........68/34
38Gy/4fx..........100/50.............90/45...........80/40

So we can see that 19/1 is biologic dose de-escalation at higher α/β's but slightly more fractionated schedules, always with the increase in total dose too, such as your 38/4 schedule are more resistant to α/β fluctuation. In this era, hypofx is ALWAYS total dose de-escalation. It is probably not biologic dose de-escalation, but it depends on how much we hypofractionate as the math above suggests.

 

[medgator]

The preferential reimbursement is not nearly as big an issue as the rates that these and similar centers can negotiate with insurance. NCI designation does not carry a benefit, it is the pps exemption for a select group of academic centers.

I thought they went hand in hand, guess not. I know the data/links have been posted on SDN before showing the increased reimbursement for those centers.

I'll try and see if I can find them again, but fwiw, I know for a fact the nearest nci designated/academic center in my neck of the woods is not in network with the lower reimbursement Medicaid/Medicare advantage plans that we are in network with.

 

[Lamount]

Why? If it stays the same, okay. If it goes down, great. If it goes up, you said it doesn't matter as an outcome.

I'd posit that if DMFS and OS are the outcomes that actually matter, you'd be best served by checking to make sure the patient is alive and ordering a bone scan periodically.

So... why are you measuring an outcome you find meaningless and has the potential to cause further harm? Unless, of course, you don't actually believe it's meaningless.

You are conflating two questions:

1) Do serial post-treatment PSAs provide useful prognostic/predictive information for individual patients? Yes. There are several studies showing that metrics such as PSADT and the interval of time before PSA begins to rise can be prognostic of clinically meaningful endpoints. However, I may be less inclined to monitor this very closely in an elderly man with GS 3+3 prostate cancer treated 10 years ago who now has end stage COPD
2) Is bPFS a meaningful clinical endpoint to judge a treatment's efficacy for all populations under all circumstances?... TBD.

Patient care and surveillance should be individualized (i.e. an appropriate surveillance plan for one patient may be inappropriate for another) whereas endpoints of a clinical trial are meant to be clinically meaningful for those who meet enrollment.

Right now, we don't know which patient population who has a biochemical failure is most likely to 1) die from prostate cancer 2) develop symptomatic metastatic disease 3) require additional therapies. Until we do, it will be hard to quantify to patients how they should expect to benefit from a more intense treatment that offers a slightly better bPFS compared to a less intense treatment

 

[Mandelin Rain]

So biochemical progression doesn't matter in patients actively dying of an unrelated issue. I will agree and raise you, that progression of any type of cancer doesn't matter if the patient is actively dying from an unrelated issue.

Yet, we all still continue to order PSA post treatment on EVERY man who is well enough to make it into clinic.

 

[scarbrtj]

So biochemical progression doesn't matter in patients actively dying of an unrelated issue. I will agree and raise you, that progression of any type of cancer doesn't matter if the patient is actively dying from an unrelated issue.

Yet, we all still continue to order PSA post treatment on EVERY man who is well enough to make it into clinic.

Sophists will always show up on the scene and say, "It's tough to make predictions, especially about the future."
One minute you think a guy is dying and the next three years later he's still perking along.
In a way, we are all actively dying; the disease is life (and it's sexually transmitted).
And what else have we besides the PSA for f/u? DRE?!?

 

[MegaVoltagePhoton]

How about people actually look at the details?

HYPO-RT-PC: Trend towards more acute grade 2 toxicity, and higher prevalence of grade 2 toxicity at 1 year.
80% had 3D-CRT planning, most patients had margins as large as 7 mm isotropically, and IGRT was not sophisticated. Yes, this applies to both arms, but given the concern with SBRT, it stands to reason that narrower margins/better targeting is more important with SBRT.

And lo and behold, if you look at PACE-B, which was the modern trial of SBRT vs IMRT (and moderate hypo), there was no difference in acute toxicity and the rate of acute toxicity is lower in the SBRT group than in the HYPO-RT-PC group.

Also I hear a lot of people saying no other specialty in medicine looks at less intensive treatments. Have those people heard of active surveillance for prostate cancer?