Post Prostate Symptoms Question

[Haybrant]

Finished treating a 63 yo man unfavorable intermediate risk prostate cancer patient in May 2017. 7920 cGy standard volumes nothing special, 180 cGy per fraction w short term ADT. He started developing diarrhea after treatment, did ok with 2-3 immodium a day. In the last 3 weeks Imodium not doing much and hes been having 8-9 BM's a day, never had blood. He was having low pelvic pain as well, tolerable but on and off throughout the day. He went to ED and they got a CTAP. This showed an edematous thickened rectum in the RT field and thickening and stranding of his bladder wall. Stool studies negative. No prior RT, no IBD history, no collagen vasc dz's. Taking Flomax qhs but has increased urinary urgency/frequency above background

Thoughts about management - I don't generally see CT's post prostate RT so I don't know what it should look like, if it was just the rectum ok but the bladder changes too? And 5 months out?

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[nkmiami]

May not be related to radiation, especially if you used image guidance. Put him on a week of steroids and probiotics.

 

[seper]

Some people do have "subacute" proctitis and cystitis after high-dose pelvic RT. I see it once in a blue moon after cervix HDR. I think this syndrome is self-limiting.

 

[evilbooyaa]

May not be related to radiation, especially if you used image guidance. Put him on a week of steroids and probiotics.

I disagree. I think toxicities from radiation are real despite best efforts. Yes the time frame isn't necessarily by the book, but inflammation 3 to 6 weeks later (not sure the exact time frame for this patient) isn't unheard of.

I'd rule out an infectious process (C. Diff and other diarrhea inducing things, as well as r/o UTI given inflammation of his bladder wall) just to cover my bases. If all are negative then you can add Lomotil as an adjunct for his diarrhea and other anti-diarrheal medications as necessary (balancing risk of constipation). If he has symptoms consistent with bladder spasms consider something like oxybutynin once UTI is ruled out, or increase dosing of alpha-blocker.

 

[medgator]

I'm surprised no one has chimed in from the sdn cost-control peanut gallery about the OP being a greedy PP for not using hypo-fractionation. Can't imagine what would have happened with this pt if he had....

 

[Burt Radnolds]

I believe it is very likely due to radiation. I have seen a handful of people who have received very standard therapy get acute proctitis/cystitis/enteritis far beyond what I would expect. When imaging has been performed in those situations, it usually shows bowel/bladder wall thickening as you described. I agree it is typically self limited and after ruling out other etiologies, supportive medication is your main tool. I did once see another provider's patient in follow up who had severe refractory chronic cystitis and proctitis, requiring two extended courses of hyperbaric.

It has been so bad once or twice that I have wondered if they had some unknown radiosensitizing mutation. Does anyone know of any assay that can be done to test for such mutations?

 

[medgator]

I believe it is very likely due to radiation. I have seen a handful of people who have received very standard therapy get acute proctitis/cystitis/enteritis far beyond what I would expect. When imaging has been performed in those situations, it usually shows bowel/bladder wall thickening as you described. I agree it is typically self limited and after ruling out other etiologies, supportive medication is your main tool. I did once see another provider's patient in follow up who had severe refractory chronic cystitis and proctitis, requiring two extended courses of hyperbaric.

It has been so bad once or twice that I have wondered if they had some unknown radiosensitizing mutation. Does anyone know of any assay that can be done to test for such mutations?

Not sure if ATM could do it, but a myriad myrisk could test for that along with a lot of other DNA repair genes which are associated with various cancer syndromes

https://new.myriadpro.com/products/myriad-myrisk/myrisk-gene-table/

Ataxia Telangiectasia

 

[Chartreuse Wombat]

I'm surprised no one has chimed in from the sdn cost-control peanut gallery about the OP being a greedy PP for not using hypo-fractionation. Can't imagine what would have happened with this pt if he had....

Happy to oblige
First i reject the premise of your question. I don't pretend to know the motivations of my colleagues. Greed need not be the motivator; some are concerned with excess toxicity (more on that later).
I am not very good with imagination but what the data tells us is as follows-
1) Hypofractionation requires fewer visits and ceteris paribus means that the treatment is more convenient for patients.
2) Efficacy is at least similar
3) The weight of the evidence is that likelihood of GI/GU toxicity is similar; yes you can point to post hoc analyses from the smaller trials but the two largest studies (CHHiP n=3200 and PROFIT=1200) provide no evidence for difference in late toxicity or QOL as reported by patients.
As such there is good evidence that moderate hypofractionation can be done without sacrificing efficacy or toxicity and it is unambiguously more convenient for patients.
To my friends who are concerned with late toxicity and state the data is not yet mature I take them at their word and don't impugn their motivations by using words like greed. I do have a question for them however. How many patients followed for how long?
Cheers

 

[medgator]

Happy to oblige
First i reject the premise of your question. I don't pretend to know the motivations of my colleagues. Greed need not be the motivator; some are concerned with excess toxicity (more on that later).
I am not very good with imagination but what the data tells us is as follows-
1) Hypofractionation requires fewer visits and ceteris paribus means that the treatment is more convenient for patients.
2) Efficacy is at least similar
3) The weight of the evidence is that likelihood of GI/GU toxicity is similar; yes you can point to post hoc analyses from the smaller trials but the two largest studies (CHHiP n=3200 and PROFIT=1200) provide no evidence for difference in late toxicity or QOL as reported by patients.
As such there is good evidence that moderate hypofractionation can be done without sacrificing efficacy or toxicity and it is unambiguously more convenient for patients.
To my friends who are concerned with late toxicity and state the data is not yet mature I take them at their word and don't impugn their motivations by using words like greed. I do have a question for them however. How many patients followed for how long?
Cheers

To be fair, it wasn't directed at you specifically, but there have been several posts/threads in this forum speaking to that.

Personally, I wouldn't dive into hypo-fractionation until we see good 15-20 year data on several thousand patients + getting ASTRO to bless it with a consensus guideline like they did with breast cancer. Switching from 1.8 to 2.8-3+/day isn't the same as going from 3d to imrt imo, which is an argument that some make.

I think the data on breast was so much more compelling, where hypofx looks to actually have a better cosmetic/toxicity profile and lower cost. The data on prostate isn't the same slam dunk

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[Palex80]

Getting back to the OP questions.
I think this is radiotherapy induced. I agree that the patient should get steroids and if not already happened, I'd do a rectoscopy to get an idea of how it looks inside.

I am not aware of any mutation tests to rule out patients having some mutation that may lead to problems.
And it's quite possible that some patients may react stronger than others when receiving radiation.

I have seen one case of DPD deficiency in a patient who was treated with 5FU and radiation for rectal cancer in the neoadjuvant setting. The patient almost died due to massive myelosuppression and heavy mucositis with resulting bacteriemia. Scary stuff. I've heard that you can test for DPD now. we didn't have a test for it back then and were not really aware of it.

 

[Chartreuse Wombat]

To be fair, it wasn't directed at you specifically, but there have been several posts/threads in this forum speaking to that.

Personally, I wouldn't dive into hypo-fractionation until we see good 15-20 year data on several thousand patients + getting ASTRO to bless it with a consensus guideline like they did with breast cancer. Switching from 1.8 to 2.8-3+/day isn't the same as going from 3d to imrt imo, which is an argument that some make.

I think the data on breast was so much more compelling, where hypofx looks to actually have a better cosmetic/toxicity profile and lower cost. The data on prostate isn't the same slam dunk

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15-20 year data? Several thousand patients well OK then.
Not what you would call an early adopter...I trust that you have adopted dose-escalation without evidence of a survival benefit...

 

[medgator]

15-20 year data? Several thousand patients well OK then.
Not what you would call an early adopter...I trust that you have adopted dose-escalation without evidence of a survival benefit...

In lieu of adt in some patients, I'd rather take dose escalation. Beyond that imrt has helped that argument.

Again, I just think it's interesting ASTRO has chimed in several times on the breast hypofx with issuing the consensus guideline and highlighting it in the choosing wisely campaign a couple years ago, yet not a peep on prostate hypofx.

Why should those of us in private practice take the risk early? Like I said compared to breast, the data in prostate is no slam dunk imo and I hypofractionate plenty on breast.

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[nkmiami]

If this is an unusual and severe XRT induced proctitis, I have found the only helpful acute treatment is steroids - an angry inflamed anorectum is causing fecal urgency. Have treated this with decadron 4mg bid or 8mg in the am only (so patient can fall asleep at night) combined with proctafoam HC. proctafoam hc likely not sufficient alone in this case.

 

[evilbooyaa]

Getting back to the OP questions.
I think this is radiotherapy induced. I agree that the patient should get steroids and if not already happened, I'd do a rectoscopy to get an idea of how it looks inside.

I am not aware of any mutation tests to rule out patients having some mutation that may lead to problems.
And it's quite possible that some patients may react stronger than others when receiving radiation.

I have seen one case of DPD deficiency in a patient who was treated with 5FU and radiation for rectal cancer in the neoadjuvant setting. The patient almost died due to massive myelosuppression and heavy mucositis with resulting bacteriemia. Scary stuff. I've heard that you can test for DPD now. we didn't have a test for it back then and were not really aware of it.

Yes that is what I was trying to google. You can test for DPD deficiency on a blood test now, IIRC.

Also, c'mon @medgator and @Chartreuse Wombat you're both better than this. Let's not turn this forum into Allo where everything gets trolled back around to the same non-sense discussion.

 

[Chartreuse Wombat]

In lieu of adt in some patients, I'd rather take dose escalation. Beyond that imrt has helped that argument.

Again, I just think it's interesting ASTRO has chimed in several times on the breast hypofx with issuing the consensus guideline and highlighting it in the choosing wisely campaign a couple years ago, yet not a peep on prostate hypofx.

Why should those of us in private practice take the risk early? Like I said compared to breast, the data in prostate is no slam dunk imo and I hypofractionate plenty on breast.

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Agree that data for breast is more compelling. ASTRO is working on a prostate hypo document. Should be published by early to mid 2018.

 

[nkmiami]

one difference between prostate and breast, is that the breast data trended towards better local control/side effects/cosmesis. it wasnt just that the treatments were equal, but the hypofractionated was possibly/maybe better.
(Not to beat a dead horse, but I cant resist- if ASTRO really gave a s### about hypofractionation, they wouldnt faciliate the oversaturation of physicians which HISTORICALLY IN ALMOST EVERY MEDICAL FIELD results in overutilization-the antithesis of their "position" statement.

Now that palex is on the thread- maybe he could tell us how many radiation oncologists are in practice in Germany. Would be interested to compare?

 

[medgator]

15-20 years!?!!?
Or, basically right around the time you’re ready to retire?
#FLORIDA

Speaking of trolls.... #hatersgonnahate

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[Palex80]

HypoFx for prostate cancer is also a topic in Europe.
There are big differences here from country to country regarding reimbursement. In some places you get reimbursed for the disease/indication you are treating while in others for the technique and the number of fractions you use.
And of course hypofractionation is going to hurt alot if you get reimbursed according to the number of fractions you treat with.

I also work in a country where the number of fractions are crucial and we have just had a big cut on reimbursement for stereotactic treatments as well as a 10% flat cut on all technical costs. In my view and from what I have heard in talks with colleagues, these cuts are going to obliterate any attempt to introduce hypofractionation as standard of care. Before the cuts, some clinics were thinking about it, but with tougher competition nowadays, people are paying attention to keeping their linacs full.
Any attempt to introduce ultra-short "cyberknife-like" SBRT for prostate cancer has also ceased to be an issue, cause you would actually ruin your clinic if you tried doing that.

We earn money for what we do. And we need to be aware that the market for primary prostate cancer RT in radiation oncology is shrinking in terms of money. Active surveillance as standard of care for low-risk tumors has already had quite an impact, I sometimes look back and wonder how many dozens of prostate patients I treated 10 years ago, that I probably shouldn't have.
Hypofractionation is going to be the next major blow.

On the other hand I have to give credit to those who oppose hypofractionation for one simple reason: The long-lasting effects of hypofractionation in prostate cancer when it comes to rectal and bladder toxicity have not been adressed in large numbers of patients with a follow up of 10+ years. The data we have comes from rather small phase II trials and it doesn't look bad. I would like though to see the 10 years toxicity data from the big randomized trials, before calling it standard of care. There's more to lose here than just a bit more teleangiectasia of the skin and soft tissue fibrosis as we feared in the breast.
Last but not least, data on hypofractionation effects to the heart in post-BCS RT are not good either. There is one paper published with 12 (?) years FU data from the START-trials, yet noone has looked at the data at 15-20 years post RT. If we offer hypofractionation to 45 year old breast cancer patients, they may experience adverse effects to the heart within a relevant time frame.

 

[medgator]

On the other hand I have to give credit to those who oppose hypofractionation for one simple reason: The long-lasting effects of hypofractionation in prostate cancer when it comes to rectal and bladder toxicity have not been adressed in large numbers of patients with a follow up of 10+ years. The data we have comes from rather small phase II trials and it doesn't look bad. I would like though to see the 10 years toxicity data from the big randomized trials, before calling it standard of care. There's more to lose here than just a bit more teleangiectasia of the skin and soft tissue fibrosis as we feared in the breast.
Last but not least, data on hypofractionation effects to the heart in post-BCS RT are not good either. There is one paper published with 12 (?) years FU data from the START-trials, yet noone has looked at the data at 15-20 years post RT. If we offer hypofractionation to 45 year old breast cancer patients, they may experience adverse effects to the heart within a relevant time frame.

Good to hear a voice of reason these forums. Personally, I don't offer hypoFx for breast for patients under 55, for the reasons you've alluded to, ASTRO i think chooses 50 as an age, but I think the data is still not there enough 20+ years out which would put a 50 year old at risk.

And yes, the potential hypo-fractionation toxicity from prostate vs breast can be far different, something that can be lost upon those who try to equalize them.

In my view and from what I have heard in talks with colleagues, these cuts are going to obliterate any attempt to introduce hypofractionation as standard of care. Before the cuts, some clinics were thinking about it, but with tougher competition nowadays, people are paying attention to keeping their linacs full.
Any attempt to introduce ultra-short "cyberknife-like" SBRT for prostate cancer has also ceased to be an issue, cause you would actually ruin your clinic if you tried doing that.

That creates an ethical quandry IMO if prostate eventually does go the way of breast hypofx. I don't know if your insurance system there has quality measures, but I can imagine insurance companies here starting to question why hypo-fx is not being used in certain scenarios, particularly in breast now, at least in terms of following the ASTRO criteria. Once there is more clarity on prostate, I could see the same thing happening there too.

As it stands now, most insurance companies won't pay more than 10 fractions/2D without IGRT (in some cases) for a bone met (and for the most part, they are correct on the 10 fractions, not on the 2D no IGRT thing)), although one could argue field size/location/PS of pt might create an argument to dose-escalate and or use SBRT.

 

[Burt Radnolds]

Last but not least, data on hypofractionation effects to the heart in post-BCS RT are not good either. There is one paper published with 12 (?) years FU data from the START-trials, yet noone has looked at the data at 15-20 years post RT. If we offer hypofractionation to 45 year old breast cancer patients, they may experience adverse effects to the heart within a relevant time frame.

Good to hear a voice of reason these forums. Personally, I don't offer hypoFx for breast for patients under 55, for the reasons you've alluded to, ASTRO i think chooses 50 as an age, but I think the data is still not safe enough 20+ years out which would put a 50 year old at risk.

Well this is spiraling quickly, guess I'll pile on. Your all's comments suggest that the heart is getting significant dose in some of your left sided hypofx patients. For me, I am able to entirely block the heart and then some in most/all patients through a variety of techniques, making the issue of late cardiac toxicity irrelevant in my opinion. If we are going to entertain the argument that the scatter dose to heart going from 50 cGy a day to 67 cGy a day is going to induce a clinical significant endpoint at any point in time then we may as well return to the Florida jokes.

 

[medgator]

Well this is spiraling quickly, guess I'll pile on. Your all's comments suggest that the heart is getting significant dose in some of your left sided hypofx patients. For me, I am able to entirely block the heart and then some in most/all patients through a variety of techniques, making the issue of late cardiac toxicity irrelevant in my opinion. If we are going to entertain the argument that the scatter dose to heart going from 50 cGy a day to 67 cGy a day is going to induce a clinical significant endpoint at any point in time then we may as well return to the Florida jokes.

I've not had a problem with the heart, and wouldn't use that as a reason to not treat someone with hypofx, but given the questions about dose and control in higher grade tumors raised in some of the studies, I sure as heck wouldn't treat a triple negative 45 y/o with it.

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[evilbooyaa]

Come on now. We're questioning breast hypofx when the main data we have suggests improved cosmesis with hypofx? Again, not saying I necessarily believe that but I'm hard pressed to believe that somehow hypofx would be WORSE than conventional.

I disagree on the need for 20 year follow-up before x becomes standard of care for any disease site. My concerns about prostate hypofx are maintained (I won't copy over the other post) showing increased acute toxicity in all of the major trials people are quoting, as well as the potential for late toxicity being worse (no real evidence to suggest that hypofx will ever be better than standard fx). I do not think hypofx RT will become standard of care

 

[medgator]

Tumor factors predictive of response to hypofractionated radiotherapy in a randomized trial following breast conserving therapy. - PubMed - NCBI

"Median follow-up was 12 years"

I disagree on the need for 20 year follow-up before x becomes standard of care for any disease site.

What do you tell the 50 y/o with prostate or breast cancer? Personally, I'm a big believer in surgery for younger men for that reason.

And getting back to the choosing wisely campaign....why would astro put an age limit of 50 as to when to consider breast hypofx?

 

[evilbooyaa]

Are you really expecting significant differences between 12 and 20 years? Is there any other scenario that has been played out in recent history where 10 year toxicity data and 20 year toxicity data are radically different?

ASTRO's guidelines are limited to >50 because the study inclusion criteria that it's based on didn't enroll patients younger than 50, or didn't enroll a high percentage of patients under 50. That's the only reason. If there was good randomized data for patients younger than 50 it would be included, but there isn't, so they can't make a consensus guideline recommend hypofractionation.

I do NOT think there is some hidden late toxicity of hypofrac that isn't apparently at 10 years that will show up at year 15, or year 20. I would be very interested to hear of one scenario where late toxicity data varied wildly between what was seen at 10 years and what was seen at 15 or 20 years.

 

[medgator]

I do NOT think there is some hidden late toxicity of hypofrac that isn't apparently at 10 years that will show up at year 15, or year 20. I would be very interested to hear of one scenario where late toxicity data varied wildly between what was seen at 10 years and what was seen at 15 or 20 years.

Recurrence rates are a function of time, are they not? That's a "toxicity" I'd be concerned about. Prostate worries me more than breast from a true toxicity standpoint. I'm worried about the toxicity to some degree in younger breast hypofx patients (not really that much considering the data is actually looking pretty good there in terms of acute effects and cosmesis) but more so, disease control as one of the hypofx studies saw an inverse outcome associated with tumor grade.

No one in PP is going to go outside of the norms/guidelines when there is no good reason to and the possibility of risk should an adverse outcome occur. I guess the cynic would say that a late recurrence can't be brought to trial thanks to statute of limitations, but still.

I guess if you work at the VA or KP though..... remember there are two sides to this issue

 

[Gfunk6]

Everyone, please cool your jets. We are not going to reach a consensus here. Politely explain your position, rebut politely and move on.

 

[DoctwoB]

Are you really expecting significant differences between 12 and 20 years? Is there any other scenario that has been played out in recent history where 10 year toxicity data and 20 year toxicity data are radically different?

ASTRO's guidelines are limited to >50 because the study inclusion criteria that it's based on didn't enroll patients younger than 50, or didn't enroll a high percentage of patients under 50. That's the only reason. If there was good randomized data for patients younger than 50 it would be included, but there isn't, so they can't make a consensus guideline recommend hypofractionation.

I do NOT think there is some hidden late toxicity of hypofrac that isn't apparently at 10 years that will show up at year 15, or year 20. I would be very interested to hear of one scenario where late toxicity data varied wildly between what was seen at 10 years and what was seen at 15 or 20 years.

I can’t speak to the role of hypofractionation but as a Urologist I can tell you I’ve seen many patients with very late onset radiation cystitis, many of which required severe measures like multiple courses of HBO, intravesical formalin, cystectomy with urinary diversion, and a couple deaths related to bladder perfs. While I obviously see a biased sample of post xrt patients, I do believe that morbidity of delayed or chronic radiation cystitis is underrecognized.

 

[evilbooyaa]

Recurrence rates are a function of time, are they not? That's a "toxicity" I'd be concerned about. Prostate worries me more than breast from a true toxicity standpoint. I'm worried about the toxicity to some degree in younger patients (not really considering the data is actually looking pretty good there in terms of acute effects and cosmesis) but more so, disease control as one of the hypofx studies saw an inverse outcome associated with tumor grade]

No one in PP is going to go outside of the norms/guidelines when there is no good reason to and the possibility of risk should an adverse outcome occur. I guess the cynic would say that a late recurrence can't be brought to trial thanks to statute of limitations, but still.

I guess if you work at the VA or KP though..... remember there are two sides to this issue

Yes, breast cancer recurrence rates do increase.... up to about 10 years. Even in looking at studies of RT vs no RT, the curves even out in slope by around 5 years. If somebody had breast cancer at 15 or 18 years after initial diagnosis, would you tell them they had recurrent breast cancer, or a new primary?

More aggressive cancers recur sooner or not at all (like TNBC showing essentially all recurrences within 3 to 5 years). Higher-grade cancers recur earlier.

In regards to bolded, I will agree that the Whelan update paper did show, on one out of the hundreds of comparisons they did, of worse recurrence rates in high-grade tumors. If you didn't want to hypofractionate early stage breast cancer that was grade 3, I would understand.

I can’t speak to the role of hypofractionation but as a Urologist I can tell you I’ve seen many patients with very late onset radiation cystitis, many of which required severe measures like multiple courses of HBO, intravesical formalin, cystectomy with urinary diversion, and a couple deaths related to bladder perfs. While I obviously see a biased sample of post xrt patients, I do believe that morbidity of delayed or chronic radiation cystitis is underrecognized.

How long after radiation was this? Greater than 10, or 12, or even 15 years after RT, where the patient was fine, and then they tanked? The only thing that continues to go up is secondary malignancy risk with radiation and time, but that would not be expected to be different between standard and hypofractionation...

 

[Haybrant]

thanks for all the responses, no UTI in the patient but I will try out steroids and see how that goes.

I can’t speak to the role of hypofractionation but as a Urologist I can tell you I’ve seen many patients with very late onset radiation cystitis, many of which required severe measures like multiple courses of HBO, intravesical formalin, cystectomy with urinary diversion, and a couple deaths related to bladder perfs. While I obviously see a biased sample of post xrt patients, I do believe that morbidity of delayed or chronic radiation cystitis is underrecognized.

I know a lot of urologists and this is essentially a 100% copy paste verbatim argument. Why not go to the IMRT data instead of relying on what old attendings tell you and what you feel.

 

[DoctwoB]

thanks for all the responses, no UTI in the patient but I will try out steroids and see how that goes.



I know a lot of urologists and this is essentially a 100% copy paste verbatim argument. Why not go to the IMRT data instead of relying on what old attendings tell you and what you feel.

The gold standard for evidence is obviously a well designed RCT and should be accepted as such. However they are not foolproof, as the very act of being on study at a high volume center means that the results are not always generalizable to a population with less strict inclusion criteria, worse compliance/follow up, and less experienced clinicians. When clinical practice findings contradict the results of RCTs , these results should be questioned and properly evaluated.

For example, within Urology in the 90s and early 2000s Transurethral Microwave Therapy and transurethral needle ablation for BPH were in vogue, as the early RCTs showed reasonably good efficacy with an in office, low morbidity procedure. They reimbursed well, and Urologists jumped all over them. Turns out that many of these patients had limited efficacy and horrible Luts post procedure, and those therapies have pretty much been abandoned. Why was real life different then the gold standard evidence? Unclear. But we do our patients a disservice if we ignore the evidence of our eyes and don’t question there literature when our practice contradicts it.

As the patients who follows post XRT patients long term I can tell you that I firmly believe the incidence of radiation cystitis and urethral stricture disease is highly underestimated. Are we biased? Of course we are, we’re surgeons that offer a competing treatment to XRT for prostate cancer. But that doesn’t mean we’re wrong.

 

[Palex80]

Are you really expecting significant differences between 12 and 20 years? Is there any other scenario that has been played out in recent history where 10 year toxicity data and 20 year toxicity data are radically different?

We do not have a lot of data on that.
An earlier paper by Darby shows that the risk seems to increase as time goes by.
Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women ... - PubMed - NCBI
If there is a true absolute "rise" after 10 years is not clear.
On the other hand we do know from pathophysiology that difference effects to the heart happen because of radiation therapy. Arteriosclerosis due to RT is something which takes time and usually happens 10+ years after treatment, not before.

 

[Palex80]

Well this is spiraling quickly, guess I'll pile on. Your all's comments suggest that the heart is getting significant dose in some of your left sided hypofx patients. For me, I am able to entirely block the heart and then some in most/all patients through a variety of techniques, making the issue of late cardiac toxicity irrelevant in my opinion. If we are going to entertain the argument that the scatter dose to heart going from 50 cGy a day to 67 cGy a day is going to induce a clinical significant endpoint at any point in time then we may as well return to the Florida jokes.

I cannot do that. We do not have deep inspiration breath hold and some patients' anatomy is bad. This means that the tangent goes through parts of the left ventricle in a small portion of my patients.
Small parts of the ventricle but still, it goes through.
The problem is, I do not know what's worse 15 years down the road. A small part of the left ventricle getting 50 / 2 or 39.9 / 2.66 ?

 

[medgator]

The problem is, I do not know what's worse 15 years down the road. A small part of the left ventricle getting 50 / 2 or 39.9 / 2.66 ?

Hopefully neither if you can achieve mean dose <3 Gy

 

[evilbooyaa]

We do not have a lot of data on that.
An earlier paper by Darby shows that the risk seems to increase as time goes by.
Long-term mortality from heart disease and lung cancer after radiotherapy for early breast cancer: prospective cohort study of about 300,000 women ... - PubMed - NCBI
If there is a true absolute "rise" after 10 years is not clear.
On the other hand we do know from pathophysiology that difference effects to the heart happen because of radiation therapy. Arteriosclerosis due to RT is something which takes time and usually happens 10+ years after treatment, not before.

Yes, I'm familiar with the Darby paper.

Do you think RT techniques from 1982 at the latest are generalizable to the current way breast cancer is treated, given the significantly more in-depth knowledge of heart dose now?

Do you believe that the way breast cancer is treated now, even in places without DIBH, prone positioning, or any other method to reduce heart dose, would treat the heart the same way as it was in 1982? Do you ever sacrifice coverage on your chest wall or whole breast to block the heart if necessary, even if slightly?

Do you believe that the difference from 180 or 200 cGy per day, to 50Gy, to the heart using current 3d planning techniques would result in less toxicity than 266 cGy per day, to 40-42.5 Gy?

If the comparison was no RT vs RT then I'd buy your argument. We're talking about whether the curves going to continue to diverge at 10, 15, 20 years out.

 

[Palex80]

Hopefully neither if you can achieve mean dose <3 Gy

Mean dose may not be the single factor which is important. You can reach a tiny mean dose by using only tangents and still irradiate a 1cm "strip" of the left ventricle with the 90% isodose. That is the point.

 

[Palex80]

Do you think RT techniques from 1982 at the latest are generalizable to the current way breast cancer is treated, given the significantly more in-depth knowledge of heart dose now?

Probably not. Yet one fact stands: Dose to the heart causes more cardiac morbidity and possibly mortality.

Do you believe that the way breast cancer is treated now, even in places without DIBH, prone positioning, or any other method to reduce heart dose, would treat the heart the same way as it was in 1982? Do you ever sacrifice coverage on your chest wall or whole breast to block the heart if necessary, even if slightly?

That is speculative, but sure, nowadays heart sparing is better than back then.

Do you believe that the difference from 180 or 200 cGy per day, to 50Gy, to the heart using current 3d planning techniques would result in less toxicity than 266 cGy per day, to 40-42.5 Gy?

Noone knows. Not 15-20 years down the road. There is simply no data on that.

 

[Haybrant]

I know that dig about following patients longterm too, I've been around a lot of urologists and the same points always come up. To the point though, Do you remember the days when surgeons would perform surgeries with butter knifes? Probably never happened, but if I took the butter knife data and said gosh I see all these patients long term with terrible complications of surgery, well **** surgery is terrible. And I held the initial referral and said to the patient, don't go to the robotic surgeon have you seen the butter knife data!

The gold standard for evidence is obviously a well designed RCT and should be accepted as such. However they are not foolproof, as the very act of being on study at a high volume center means that the results are not always generalizable to a population with less strict inclusion criteria, worse compliance/follow up, and less experienced clinicians. When clinical practice findings contradict the results of RCTs , these results should be questioned and properly evaluated.

For example, within Urology in the 90s and early 2000s Transurethral Microwave Therapy and transurethral needle ablation for BPH were in vogue, as the early RCTs showed reasonably good efficacy with an in office, low morbidity procedure. They reimbursed well, and Urologists jumped all over them. Turns out that many of these patients had limited efficacy and horrible Luts post procedure, and those therapies have pretty much been abandoned. Why was real life different then the gold standard evidence? Unclear. But we do our patients a disservice if we ignore the evidence of our eyes and don’t question there literature when our practice contradicts it.

As the patients who follows post XRT patients long term I can tell you that I firmly believe the incidence of radiation cystitis and urethral stricture disease is highly underestimated. Are we biased? Of course we are, we’re surgeons that offer a competing treatment to XRT for prostate cancer. But that doesn’t mean we’re wrong.

 

[DoctwoB]

You’re right that these patients with long term complications of XRT weren’t receiving today’s technology or protocols, but can you honestly say in an evidence based fashion that IMRT has a significantly lower long term complication rate then 3D conformal (asking honestly, not sure of data).

To go back to your analogy, that could be like saying that Robotic surgeons are claiming that incontinence data doesn’t apply to them because they use a new superior technique. Only a robotic prostatectomy has never been proven superior to open prostatectomy except in secondary measures like blood loss.

 

[RadOncDoc21]

You’re right that these patients with long term complications of XRT weren’t receiving today’s technology or protocols, but can you honestly say in an evidence based fashion that IMRT has a significantly lower long term complication rate then 3D conformal (asking honestly, not sure of data).

To go back to your analogy, that could be like saying that Robotic surgeons are claiming that incontinence data doesn’t apply to them because they use a new superior technique. Only a robotic prostatectomy has never been proven superior to open prostatectomy except in secondary measures like blood loss.

Dose is dose, if one can limit the amount of it, chances are toxicities will go down. This has been proven in almost every study comparing IMRT to 3D. This is why IMRT is approved for use in prostate cancer. As technology gets better, IGRT, motion detection, less dose to the bladder and rectum.

Don’t get me wrong, there will be patients who develop significant toxicty, but very few.

 

[DoctwoB]

Dose is dose, if one can limit the amount of it, chances are toxicities will go down. This has been proven in almost every study comparing IMRT to 3D. This is why IMRT is approved for use in prostate cancer. As technology gets better, IGRT, motion detection, less dose to the bladder and rectum.

Don’t get me wrong, there will be patients who develop significant toxicty, but very few.

Protons too? That limits dose. I’ll wait. IMRT (and any device/non pharmaceutical) was approved because it met safety guidelines, not because it demonstrated superiority.

Theory is a poor substitute for data.

 

[medgator]

Protons too? That limits dose. I’ll wait. IMRT (and any device/non pharmaceutical) was approved because it met safety guidelines, not because it demonstrated superiority.

Theory is a poor substitute for data.

Cost differential of imrt vs 3D is far closer than protons vs imrt.

 

[RadOncDoc21]

Protons too? That limits dose. I’ll wait. IMRT (and any device/non pharmaceutical) was approved because it met safety guidelines, not because it demonstrated superiority.

Theory is a poor substitute for data.

Why do we even track dose and do treatment planning? Why should we block critical structures? Why do we care if one organ receives greater than 110% of the prescribed dose? Is radiation just a theory also?

Protons do have a place in our field and we use it for a lot of situations including re-treatments, peds, and possibly skull base tumors. It may not be a good substitute for definitive RT to the prostate, but if you believe in dose, than you should believe in “theory.”

The only other thing I would suggest is to talk with your radiation oncologist and ask them why are their patients experiencing severe long-term cystitis following treatment? As others have mentioned and from what “data” exists, it’s not as common as you‘ve stated.

 

[evilbooyaa]

Protons too? That limits dose. I’ll wait. IMRT (and any device/non pharmaceutical) was approved because it met safety guidelines, not because it demonstrated superiority.

Theory is a poor substitute for data.

Rates of acute toxicity are, across the board in Radiation Oncology, reasonable predictors of late toxicity. Decrease one, you decrease the other.
Rates of acute toxicity are lowered with IMRT compared to 3D. Protons has not shown that benefit, at least not as of yet.

Quick pubmed search finds this: Comparing morbidity and cancer control after 3D-conformal (70/74 Gy) and intensity modulated radiotherapy (78/82 Gy) for prostate cancer. - PubMed - NCBI

3D to a lower dose had the same rates of late GU toxicity as IMRT to a higher dose, and lower late GI toxicity, all while improving outcomes due to the benefit of dose escalation.

There is no data like this, that I am aware of, comparing IMRT vs Protons, with sufficient follow-up for discussion of late toxicity.

 

[Haybrant]

A little different turn here. Got a old guy, like 92 with prostate cancer, he never had definitive therapy and has been on ADT then enza/niluta etc. His urinary sxs have been pretty bad and med onc has been pushing for palliative RT. His prostate is very large and bladder very small. Time is a big issue for him and he wont agree to more than 2 wks. Was going to 300 x 10 but also concerned I might push him into obstruction, any other thoughts on fractionation, does it even really matter. Maybe 250 x 10? Appreciate the thoughts

 

[BobbyHeenan]

A little different turn here. Got a old guy, like 92 with prostate cancer, he never had definitive therapy and has been on ADT then enza/niluta etc. His urinary sxs have been pretty bad and med onc has been pushing for palliative RT. His prostate is very large and bladder very small. Time is a big issue for him and he wont agree to more than 2 wks. Was going to 300 x 10 but also concerned I might push him into obstruction, any other thoughts on fractionation, does it even really matter. Maybe 250 x 10? Appreciate the thoughts

I'd put him on pre-treatment flomax if he can tolerate it and consider a medrol dose pack as well. For 10 fractions I'd actually probably go 35 in 10. I"m not sure you're going to see much shrinkage/relief of symptoms with anything lower than 30 in 10. Obviously, you don't want to hurt this guy, but I think likelihood of much response at 2.5 X 10 is low. I'm obviously no expert on this though, just my stream-of-consciousness thoughts.

I did treat a couple of patients like this in training, and we typically did 50 Gy in 20 fractions in this instance.

 

[MegaVoltagePhoton]

To be fair, it wasn't directed at you specifically, but there have been several posts/threads in this forum speaking to that.

Personally, I wouldn't dive into hypo-fractionation until we see good 15-20 year data on several thousand patients + getting ASTRO to bless it with a consensus guideline like they did with breast cancer. Switching from 1.8 to 2.8-3+/day isn't the same as going from 3d to imrt imo, which is an argument that some make.

I think the data on breast was so much more compelling, where hypofx looks to actually have a better cosmetic/toxicity profile and lower cost. The data on prostate isn't the same slam dunk

Sent from my SAMSUNG-SM-N910A using SDN mobile

As a disclaimer I actually respect some of the vocal posters who aren't in favor of prostate hypofrac (like medgator for instance) but in this case I find that things are somewhat misinterpreted.

Let's look at the data, the 3 isoeffective studies (non-inferiority)
--PROFIT: median f/u of 6 years, more acute toxicity with hypofrac but more late toxicity with conventional frac (this result is ignored by people who do not support hypofrac). An anyway, pray tell what the increased acute risk is? Grade 2 or greater, 1.3% vs 2.3%. That's a 0.8% difference. The increase in late toxicity with conventional fractionation is more (1.5% vs 2.9%, or 1.4% difference).

--RTOG 0415: Yes, true, more late grade 2 GI (11.4 vs >18.3%, or 6.9%) and late grade 2 GU (20.5 vs 26.2, or 5.7%). However, the conventional arm treated with 73.8 Gy. We already know from dose escalation studies that at least grade 2 GI toxicity will be significantly higher with dose escalation. Why is this point ignored? The results very likely would have been different if it were 79.2 or 81 Gy vs 70/28, and we all know it. Yet that point is ignored, too. Also, the PI of the study admits there were very lax dosimetric constraints. And even with all this, we're talking about an absolute toxicity increase of <7%. It's not nothing, but someone readings these posts would think it's like a 20% increase in toxicity. Not even close.

--CHHIP: Median followup of 5 years. More acute grade ≥2 GI toxicity with hypofractionation (25% vs. 38% vs. 38%). More late grade ≥2 GI toxicity with conventional than with 57 Gy (4% vs. 2%; 3% in 60 Gy). No difference in acute or late grade ≥2 GU toxicity. So fine, the acute GI toxicity is real (it was seen in PROFIT, too) and can be of up to 13% in magnitude. Ok. Well, if the old refrain is that acute toxicity predicts late toxicity, why does this difference not persist? Why is it shortlived?

So anyway, in my opinion, one could look at these 3 trials at least, and say well acute toxicity is worse, on the order of 2-15% worse. Late toxicity is a mixed bag -- worse with conventional in one trial, worse with hypo in one trial (which had a flawed, low dose competing arm), and at the least equiivalent.

ASTRO is even releasing a consensus statement supporting the use of hypofrac, which broadly supports its use in all risks groups if nodes aren't being treated.

 

[medgator]

ASTRO is even releasing a consensus statement supporting the use of hypofrac, which broadly supports its use in all risks groups if nodes aren't being treated.

And I think that's when you'll start seeing more uptake. Also awaiting the updated breast guidelines.

 

[DoctwoB]

A little different turn here. Got a old guy, like 92 with prostate cancer, he never had definitive therapy and has been on ADT then enza/niluta etc. His urinary sxs have been pretty bad and med onc has been pushing for palliative RT. His prostate is very large and bladder very small. Time is a big issue for him and he wont agree to more than 2 wks. Was going to 300 x 10 but also concerned I might push him into obstruction, any other thoughts on fractionation, does it even really matter. Maybe 250 x 10? Appreciate the thoughts

Another patient for whom I'll throw the surgery hat into the ring. If his symptoms are predominantly storage based radiation is likely to worsen, not improve sx. If his symptoms are obstructive, then a channel TURP will be more effective and treat him most rapidly. Can be done under spinal if comorbidity or GA is a concern.