High risk prostate fractionation

[evilbooyaa]

*sigh*

*puts on linen shirt, grabs crystal necklace, lights incense*

Counter to what feels like, well, everyone else in RadOnc does (especially oral boards), I try to never discuss actual trial numbers with patients.

Obviously, if really pressed and the person seems like they have the "health literacy" to understand what the numbers mean, I'll do it.

But the human brain does not natively understand the abstract concept of a population-level statistics. If that were true, no one would ever play Powerball. Additionally, people will absolutely latch onto a number if a doctor says it. A couple of weeks ago, I had a consult where a guy told me he only had 7 months left to live, and asked why he should get radiation if he was going to die so soon. On trying to figure out how he arrived at that belief, it sounds like someone in MedOnc gave him an estimate on what would happen if he elected to not receive any treatment, and by the time he got to me, he figured he should be ordering a casket.

I phrase things in various ways:

"How long do I have left to live" is discussed with the "hours to days, days to weeks, weeks to months, months to years" timeline.

"Are you going to cure my cancer" is discussed more organically, but I often say things such as "very good chance, good chance, 50/50, maybe 50/50 but it's worth a shot", etc (I modify this based on the literacy of the person I'm talking to).

For side effects, I go with "best case scenario, worst case scenario, and most likely scenario".

So, with that hippie context, when I get to the side effects portion of the consult, after discussing the more common side effects, I truthfully tell them that the most likely scenario is that guys tell me they feel a little tired, and that they have some more urinary urgency/frequency and/or difficulty starting to urinate, but get through from start to finish without severe issues (I don't know about y'all, but that's how my prostate courses usually go...even though I refuse to use the beloved SpaceOAR, I don't see much in the way of GI toxicity - sorry Boston Scientific).

After telling them the "most likely" scenario, I then tell them (again, truthfully) that the guys who do the shorter course regimen generally experience slightly more urgency/frequency earlier than the longer course patients, but they also have no trouble getting through. I then reiterate/summarize with something like "that's the choice, both options should have an equally excellent chance at controlling the cancer, and the tradeoff for being done faster is a slightly increased chance of some urinary side effects showing up earlier and maybe being a little more bothersome". I often make a stupid joke like "can't get anything for free in this world, right?" and then the three of us laugh (because there's usually a wife in the room).

That's all I say. No numbers, no doom and gloom. I'm absolutely CERTAIN that if I tried this in a department in a downtown metro area with someone driving in from the suburbs, I would have almost no one picking conventional, haha.

On my end, as I've said on SDN before: I vastly prefer conventional fractionation for psych/mental health reasons. Prostate patients are a nervous bunch. You get these older men who grew up in an era when men weren't supposed to show emotion, so they don't have great coping mechanisms. They're often generally healthy, so this is their first "real" big health issue. You can see the terror in their eyes, but they're trying to hold it in.

So you take someone like that, and you start them on a treatment they don't understand. Eventually, the treatment becomes "routine" for them, and the anxiety lessens.

EXCEPT if urinary side effects show up in Week 2, which is not uncommon in my experience (and consistent with the literature). Then it's just week after week of trying to dial in Flomax or whatever, and the anxiety is always lurking.

With conventional, if urinary side effects show up, it's usually in the final 10-14 days. By that point, guys have already "settled in" and it's MUCH easier to manage.

So...yeah. I'm a secret super hippie and like to use phrases such as "most likely" a lot. But I've had this conversation, and offered this choice, to a couple hundred prostate patients. None of these things I've observed are easily quantifiable, of course. But I hope the eviCores and AIMs of the world don't completely take away my ability to conventionally fractionate before I publish this in The Journal of New Age Chakra Radiation Doctors n' Stuff.

You're counseling patients on increased rate of acute GU toxicity with mod hypofx? Besides the anecdotes presented here, data for that with 70/28 or 60/20 regimens? Acute GI toxicity, yes, I counsel based on ASTRO Prostate HypoFx guidelines.... but what's your evidence for worse acute GU toxicity?

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[TheWallnerus]

You're counseling patients on increased rate of acute GU toxicity with mod hypofx? Besides the anecdotes presented here, data for that with 70/28 or 60/20 regimens? Acute GI toxicity, yes, I counsel based on ASTRO Prostate HypoFx guidelines.... but what's your evidence for worse acute GU toxicity?

I think late toxicity is reasonably well estimated with alpha/beta calcs. As is cell kill. However a simple alpha/beta calc leaves much to be desired when estimating acute toxicity differences between 9 week and 1 week regimens that on paper are supposedly isotoxic. And actually, on paper, every single hypfractionated regimen is supposed to have LESS acute toxicity than normofract regimens (calculated with alpha/beta=10 eg). On paper is different than in clinic (of course one could say with a sufficiently correct model, paper would match clinic!). Ignoring time and really understanding how significantly manipulating it affects radiation therapy outcomes is too unexamined.

 

[evilbooyaa]

I think late toxicity is reasonably well estimated with alpha/beta calcs. As is cell kill. However a simple alpha/beta calc leaves much to be desired when estimating acute toxicity differences between 9 week and 1 week regimens that on paper are supposedly isotoxic. And actually, on paper, every single hypfractionated regimen is supposed to have LESS acute toxicity than normofract regimens (calculated with alpha/beta=10 eg). On paper is different than in clinic (of course one could say with a sufficiently correct model, paper would match clinic!). Ignoring time and really understanding how significantly manipulating it affects radiation therapy outcomes is too unexamined.

Forget a/b for a second. Where in clinical data (like in real patients) with recommended mod hypofx regimens (NOT HYPRO regimen) are we seeing acute GU toxicity at higher rates than conventional fx?

I've posted extensively about mod hypo fx for prostate in the past, and have done multiple deep dives into the literature, and I just want to know if there is evidence behind an increase in acute GU toxicity- I already counsel on increase in acute GI toxicity. Because if it's there evidence there then I want to mention it. And if it's just dogmatic anecdotal voodoo that flies in the face of pretty much all the major prostate hypofx trials then I'd be interested in that as well.

 

[TheWallnerus]

Forget a/b for a second. Where in clinical data (like in real patients) with recommended mod hypofx regimens (NOT HYPRO regimen) are we seeing acute GU toxicity at higher rates than conventional fx?

I've posted extensively about mod hypo fx for prostate in the past, and have done multiple deep dives into the literature, and I just want to know if there is evidence behind an increase in acute GU toxicity- I already counsel on increase in acute GI toxicity. Because if it's there evidence there then I want to mention it. And if it's just dogmatic anecdotal voodoo that flies in the face of pretty much all the major prostate hypofx trials then I'd be interested in that as well.

Actually (maybe it wasn’t clear) I’m saying a/b would say: less acute tox with hypofx. Like, a lot less potentially. However, anecdotally, I almost always see a brisker and quicker acute toxicity peak as the package treatment time compresses. YMMV.

 

[madchemist89]

I've done lots of 28 fx prostate treatments. GI and GU acute toxicity is minimal. I've personally noticed no difference compared to conventional. I also use the updated constraints from Duke, so they are more stringent than those from the original rtog trial.

 

[elementaryschooleconomics]

You're counseling patients on increased rate of acute GU toxicity with mod hypofx? Besides the anecdotes presented here, data for that with 70/28 or 60/20 regimens? Acute GI toxicity, yes, I counsel based on ASTRO Prostate HypoFx guidelines.... but what's your evidence for worse acute GU toxicity?

Figure 4B from CHHiP?

I don't mean "statistically significant overall increase in acute GU toxicity in a Phase III RCT".

I mean exactly what is shown at Week 2 from CHHiP.

As I said before here and elsewhere:

1) A lot of guys have high anxiety at consult and beginning of treatment.
- no, I don't have a trial to cite for "a lot"
2) I try to be very consistent with the "relatively full bladder" instructions.
- this is something most people have never been asked to do in their lives and adds more stress
3) Acute GU toxicity shows up earlier in mod hypo.

I forgot about the CHHiP supplement (p18, B):

I am absolutely not a "mod hypo hater" - the publications on my CV would be ironic, if that were the case.

When I talk about this to patients (or in general) - I am intentionally using colloquial language such as "a little more bothersome" precisely because I am not reciting trial data.

I mean that the way patients "perceive" acute GU toxicity is very different on Week 2 vs Week 5. In my experience, it will take guys the first 5 days or so (Week 1) to really dial in the routine in terms of bladder filling and adjusting to "the process". For even the highly anxious guys, if we can make it to the third OTV without side effects, they are noticeably more relaxed.

But anxious guys with bladder filling instructions noticing even mild GU symptoms on Week 2? That's definitely "more bothersome" than the guy hanging out with the staff on Week 6 telling me he "made it this far, it's not that bad".

Of course, I would absolutely take the guy who shows up in my office with a printout of some mod hypo article telling me he wants 60/20 any day of the week. The motivated guys who have already mentally committed to it are a breeze.

I'm not aware of data on this, no. This is not easy to measure, because we're really bad about this "soft" stuff. We're great at spitting out p-values from big trials with physician-graded toxicity scales. But quantifying the emotional duress of a 72-year-old guy who was taught that "real men don't cry" and thinks cancer only happens to people who don't "live right" as it pertains to the type, timing, and severity of side effects...there's no CTCAE scale for that.

 

[Chartreuse Wombat]

Figure 4B from CHHiP?

View attachment 358637

I don't mean "statistically significant overall increase in acute GU toxicity in a Phase III RCT".

I mean exactly what is shown at Week 2 from CHHiP.

As I said before here and elsewhere:

1) A lot of guys have high anxiety at consult and beginning of treatment.
- no, I don't have a trial to cite for "a lot"
2) I try to be very consistent with the "relatively full bladder" instructions.
- this is something most people have never been asked to do in their lives and adds more stress
3) Acute GU toxicity shows up earlier in mod hypo.

I forgot about the CHHiP supplement (p18, B):

View attachment 358638

I am absolutely not a "mod hypo hater" - the publications on my CV would be ironic, if that were the case.

When I talk about this to patients (or in general) - I am intentionally using colloquial language such as "a little more bothersome" precisely because I am not reciting trial data.

I mean that the way patients "perceive" acute GU toxicity is very different on Week 2 vs Week 5. In my experience, it will take guys the first 5 days or so (Week 1) to really dial in the routine in terms of bladder filling and adjusting to "the process". For even the highly anxious guys, if we can make it to the third OTV without side effects, they are noticeably more relaxed.

But anxious guys with bladder filling instructions noticing even mild GU symptoms on Week 2? That's definitely "more bothersome" than the guy hanging out with the staff on Week 6 telling me he "made it this far, it's not that bad".

Of course, I would absolutely take the guy who shows up in my office with a printout of some mod hypo article telling me he wants 60/20 any day of the week. The motivated guys who have already mentally committed to it are a breeze.

I'm not aware of data on this, no. This is not easy to measure, because we're really bad about this "soft" stuff. We're great at spitting out p-values from big trials with physician-graded toxicity scales. But quantifying the emotional duress of a 72-year-old guy who was taught that "real men don't cry" and thinks cancer only happens to people who don't "live right" as it pertains to the type, timing, and severity of side effects...there's no CTCAE scale for that.

Pay me now or pay me later

 

[elementaryschooleconomics]

View attachment 358645
Pay me now or pay me later

Did you...read my post lol

 

[elementaryschooleconomics]

 

[RickyScott]

View attachment 358645
Pay me now or pay me later

Alan pollacks phase 3 hypofract study also reported similar results.

 

[Chartreuse Wombat]

View attachment 358646

I don't accept your premise that perception changes from week 2 to week 5. I am happy to see evidence to support your statement.

In my experience "perception" can be influenced by how the issue is framed.

 

[Palex80]

What matters is the area under the curve, when it comes to how many symptoms normofractionated or hypofractionated treatment causes.
And the AUC looks about the same, the distribution over time is what differs.

 

[evilbooyaa]

Figure 4B from CHHiP?
*snip*

Here is the part of your post I previously bolded, and what I have left bolded you still have not shown evidence of:

"shorter course regimen generally experience slightly more urgency/frequency earlier than the longer course patients, but they also have no trouble getting through. I then reiterate/summarize with something like "that's the choice, both options should have an equally excellent chance at controlling the cancer, and the tradeoff for being done faster is a slightly increased chance of some urinary side effects showing up earlier and maybe being a little more bothersome"

There is no difference in severity of acute GU toxicity during radiation. There is no difference in the peak (as is seen with acute GI toxicity), and there is no difference in the area under the curve.

You want to say that patients get toxicities earlier, fine so be it.

I really think reassuring a prostate patient getting mod hypofx that he's going to be OK in terms of his GU toxicities (when he gets them at week 2 or 3) is the real answer here. And really, the OTV is "well might be a little bit because of RT, can offer you flomax if you want it" and the patients will realize the bother is not so much that it warrants medications (which is the definition of a CTCAE G1 GU toxicity)

I don't personally think, that instead of simply managing a patient's expectations, we should simply give him 50% more treatments, which, oh by the way, wink wink, helps us to be paid more. If a patient is choosing prostate RT w/ conventional fractionation, I would want them to know the severity of their urinary side effects will be the same. Their chances at acute GI toxicity and severity will be less. The downside (for the patient) is that they have to come in more times.

I've met a ton of 'anxious' prostate patients who just need hand holding and reassurance.

 

[TheWallnerus]

I really think reassuring a prostate patient getting mod hypofx that he's going to be OK in terms of his GU toxicities (when he gets them at week 2 or 3) is the real answer here.

Evil…

Sometimes I need as much reassurance as the patient needs as selfish as that is

 

[evilbooyaa]

Evil…

Sometimes I need as much reassurance as the patient needs as selfish as that is

Let the experiences of the thousands of patients across multiple mod hypofrac prostate trials be your reassurance.

 

[TheWallnerus]

Let the experiences of the thousands of patients across multiple mod hypofrac prostate trials be your reassurance.

I'm too solipsistic for that I guess

 

[evilbooyaa]

I'm too solipsistic for that I guess

My (seemingly) monthly google of a term that Wallnerus used, to help all those like myself who do not have the english vocabulary wielded, sharper than a sword, by Wallnerus.

Definition of solipsistic​

adjective
of or characterized by solipsism, or the theory that only the self exists, or can be proved to exist:Her treatment philosophy dealt with madness as a complete, self-contained, solipsistic world that sane people are not able to enter.

 

[SneakyBooger]

I vote for SneakerBooger for SDN poster of the year for promoting arthritis treatment and now leading the 'resistance' against the ridiculous NCCN and ASTRO crusade against effective and safe conventionally fractionated radiation for prostate cancer. In addition to the compelling evidence presented, I would add that conventionally fractionated radiation to 74 Gy in 37 fractions was shown in the ProtecT trial to be equally effective and less toxic compared to radical prostatectomy with 10 year follow-up.

I 'wonder' why NCCN and ASTRO would so aggressively promote a treatment which is certainly not more effective than the previous standard of care and is possibly more toxic.

@scarbrtj deserves all the credit for introducing SDN to the greatest thing since sliced bread for rad onc - arthritis! But thank you anyway.

NCCN and ASTRO (and I would add NRG) may not be here entirely for the betterment of rad oncs or our patients. See post on socialized medicine in Canada (Oh Canada, here we come...? Evicore leading the way...)

 

[TheWallnerus]

I vote for SneakerBooger for SDN poster of the year for promoting arthritis treatment and now leading the 'resistance' against the ridiculous NCCN and ASTRO crusade against effective and safe conventionally fractionated radiation for prostate cancer. In addition to the compelling evidence presented, I would add that conventionally fractionated radiation to 74 Gy in 37 fractions was shown in the ProtecT trial to be equally effective and less toxic compared to radical prostatectomy with 10 year follow-up.

Shorter fractionation schemes benefit academic centers that are often seeing and potentially treating out of towners, higher costs are never an issue in these studies and it's easier to be blissfully ignorant about the elephant in the room.

NCCN and ASTRO (and I would add NRG) may not be here entirely for the betterment of rad oncs or our patients.

Pro tip on Medicare Advantage patients who may get standard fractionatation for their prostate cancer denied by benefit managers on the front end... have the member appeal the decision, and have them print out the NCCN guideline which shows 45 fractions for all stages as acceptable (yes it shows eg 28 fraction preferred etc etc but std fx is acceptable for all stages per NCCN) to send in with the appeal. The denial will be overturned every time.

 

[SneakyBooger]

Pro tip on Medicare Advantage patients who may get standard fractionatation for their prostate cancer denied by benefit managers on the front end... have the member appeal the decision, and have them print out the NCCN guideline which shows 45 fractions for all stages as acceptable (yes it shows eg 28 fraction preferred etc etc but std fx is acceptable for all stages per NCCN) to send in with the appeal. The denial will be overturned every time.

I would add that conventional fractionation is also designated as "Preferred":

Also, I am a very much "the glass is half full" kind of person, but have I mentioned that I harbor exceptional feelings for any rad onc that ever worked for Evicore?

 

[medgator]

Pro tip on Medicare Advantage patients who may get standard fractionatation for their prostate cancer denied by benefit managers on the front end... have the member appeal the decision, and have them print out the NCCN guideline which shows 45 fractions for all stages as acceptable (yes it shows eg 28 fraction preferred etc etc but std fx is acceptable for all stages per NCCN) to send in with the appeal. The denial will be overturned every time.

Send in aua Astro fx guidelines as well.

Evilcore hasn't denied a conventional fx case for me in awhile. Some payors will only approve 40 rather than 45 fx though

 

[SneakyBooger]

All my prostates get 180.

One of my friends across town treats with everything that they can, including spacer and SBRT.

Yet I continue to see more prostates than any other rad onc in the region. Maybe it is just that I have been here a long time and built up a lot of trust.

The urologists have many times commented that they see more toxicity when their patients are treated elsewhere.

It would be imprudent to change that.

Buy who knows, maybe things will change - every dog has their day.

@RickyScott, I do believe you when you say you see more toxicity with 200.

I am pretty sure I have a paper looking at 180 vs 200 - let me see if I can find it.

To add to this thread another little bit of insight to the world of rad onc...

This morning I got a call from the senior doc at another (smaller) urology group in town today complaining about all the post RT bladder problems they are seeing. He states that all of problems come from one rad onc, the hypofractionator. He requests that I see all of his prostate pts and no one else in town. I inform him I will get them in as soon as I possibly can.

The problem for the hypofractionator is once that bridge is burned it is very very hard to rebuild.

 

[TheWallnerus]

To add to this thread another little bit of insight to the world of rad onc...

This morning I got a call from the senior doc at another (smaller) urology group in town today complaining about all the post RT bladder problems they are seeing. He states that all of problems come from one rad onc, the hypofractionator. He requests that I see all of his prostate pts and no one else in town. I inform him I will get them in as soon as I possibly can.

The problem for the hypofractionator is once that bridge is burned it is very very hard to rebuild.

Hypofractionators.

 

[Linaculous]

FYI More data for hypofrac for high-risk incoming w/ PCS5 at ASTRO:

Annual Meeting 2022

plan.core-apps.com

 

[Fpg1245]

FYI More data for hypofrac for high-risk incoming w/ PCS5 at ASTRO:

Annual Meeting 2022

plan.core-apps.com

Thank goodness I stopped wasting my time

 

[OTN]

50% increase in Grade 2 toxicity at 5 years with hypofractionation to prostate only, but something tells me that's not going to be the takeaway from the trial:

DEFINE_ME

 

[TheWallnerus]

50% increase in Grade 2 toxicity at 5 years with hypofractionation to prostate only, but something tells me that's not going to be the takeaway from the trial:

DEFINE_ME

One of the most important developments in the uptake of hypofractionation for prostate cancer in radiation oncology was the intentional ignoring of the differing rates of grade 0/1/2 toxicity in patients treated with hypofract vs std fract; it was the deciding advancement in GU in rad onc in the last 20y imho

 

[elementaryschooleconomics]

One of the most important developments in the uptake of hypofractionation for prostate cancer in radiation oncology was the intentional ignoring of the differing rates of grade 0/1/2 toxicity in patients treated with hypofract vs std fract; it was the deciding advancement in GU in rad onc in the last 20y imho

I think the increasing recognition of how flawed "physician-judged toxicity" is as a metric will change practice patterns for many specialties in the coming decades. I had "moderate hypofrac is the moral highroad" shoved down my throat for years. I've obviously planted my flag several times in this thread so I won't beat the drum again, but I would choose conventional frac for myself.

The drum worth beating, in my opinion, is continued caution against comparing hypofrac regimens between different disease sites. While I would personally choose conventional for prostate, I think hypofrac for breast is amazing and basically exclusively use it. I have never found a compelling reason to use conventional for intact breasts, and have never used it in my practice.

My boomer partners are a different story. Every time I cover their breast OTVs, my decision to never use conventional for breast is affirmed.

 

[DoctwoB]

One of the most important developments in the uptake of hypofractionation for prostate cancer in radiation oncology was the intentional ignoring of the differing rates of grade 0/1/2 toxicity in patients treated with hypofract vs std fract; it was the deciding advancement in GU in rad onc in the last 20y imho

There is also the effect of comparing treatments in stepwise fashion. 20 fractions is compared to standard with higher tox but meets the non-inferiority threshold. 5 is compared to 20 with higher tox but meets the non-inferiority threshold. And so on with 1 or 3 to 5. But no one compares 5 to conventional or 1/3 to conventional. Just keep boiling the frog.

 

[communitydoc13]

There is also the effect of comparing treatments in stepwise fashion. 20 fractions is compared to standard with higher tox but meets the non-inferiority threshold. 5 is compared to 20 with higher tox but meets the non-inferiority threshold. And so on with 1 or 3 to 5. But no one compares 5 to conventional or 1/3 to conventional. Just keep boiling the frog.

What's your take from clinical experience? We all have our biases but few of us follow prostates more than 2-5 years out if they have Urology on board. Have you seen a different late side effect profile going from 44-28-20-5?

 

[DoctwoB]

What's your take from clinical experience? We all have our biases but few of us follow prostates more than 2-5 years out if they have Urology on board. Have you seen a different late side effect profile going from 44-28-20-5?

Small N, but definitely see more irritative GU side effects from SBRT. Hard to compare conventional to 20 fractions since not many get conventional and there is a lot of brachy monotherapy or brachy boost for higher risk in my region.

 

[elementaryschooleconomics]

There is also the effect of comparing treatments in stepwise fashion. 20 fractions is compared to standard with higher tox but meets the non-inferiority threshold. 5 is compared to 20 with higher tox but meets the non-inferiority threshold. And so on with 1 or 3 to 5. But no one compares 5 to conventional or 1/3 to conventional. Just keep boiling the frog.

Preach. It's like the 501(k) device approval pathway at the FDA.