What am I missing about the ProtecT trial

[vpras1234]

Hi folks,

I'm a current applicant in Urology, and I was reading about Prostate Cancer, when I cam across the ProtecT trial

"10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer" (sorry, SDN wont let me post link

It suggests that the Prosate Cancer specific group between AS, ADT+Radiation Therapy, and Prostatectomy are essentially identical (Figure 3). And while both RP and ADT+RT are superior to Active Surveillance in Freedom from disease progression, the two treatments are essentially identical in that measure.

NNT to avoid metastatic disease for RP is 27, while ADT+RT is 33.

And then I read the Patient Reported Outcomes Paper: "Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer"

Here, RP has worse incontinence reported with regards to pads per day and worse Sexual Bother scores, while ADT+ XRT has worse nocturia and bloody stools.

So from this data, it seems to suggest that ADT+RT is equivalent to RP. Then why do Urologists perform RP at all? Are the bloody stools from XRT so bad that physicians recommend surgery instead?

Thanks

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[FindMeOnTheLinks]

Some dudes can't/don't want to put up with 8 weeks of radiation treatment and decide that getting it done in a day is worth the side effects

Or their urologist convinces them Radiation isnt as great as it sounds so they never see a radiation oncologist

 

[OneTwoThreeFour]

Some dudes can't/don't want to put up with 8 weeks of radiation treatment and decide that getting it done in a day is worth the side effects

Or their urologist convinces them Radiation isnt as great as it sounds so they never see a radiation oncologist

Or each urologist assures their patient that their outcomes are much better.
Or the urologist has been doing RPs for 30 years and hasn't adopted the XRT methods.
Gotta say, though. After a year or so of prostate cancer research I'm an active surveillance fan myself...

 

[Frogger27]

Or each urologist assures their patient that their outcomes are much better.
Or the urologist has been doing RPs for 30 years and hasn't adopted the XRT methods.
Gotta say, though. After a year or so of prostate cancer research I'm an active surveillance fan myself...

Depends what Age, race, gleason score, etc....

 

[vpras1234]

Or each urologist assures their patient that their outcomes are much better.
Or the urologist has been doing RPs for 30 years and hasn't adopted the XRT methods.
Gotta say, though. After a year or so of prostate cancer research I'm an active surveillance fan myself...

For real. The 10 year disease progression free survival is pretty impressive for AS

 

[vpras1234]

Are there any other head to head RCTs for Radiation vs surgery?

 

[deleted18755]

Hi folks,

I'm a current applicant in Urology, and I was reading about Prostate Cancer, when I cam across the ProtecT trial

"10-Year Outcomes after Monitoring, Surgery, or Radiotherapy for Localized Prostate Cancer" (sorry, SDN wont let me post link

It suggests that the Prosate Cancer specific group between AS, ADT+Radiation Therapy, and Prostatectomy are essentially identical (Figure 3). And while both RP and ADT+RT are superior to Active Surveillance in Freedom from disease progression, the two treatments are essentially identical in that measure.

NNT to avoid metastatic disease for RP is 27, while ADT+RT is 33.

And then I read the Patient Reported Outcomes Paper: "Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy for Prostate Cancer"

Here, RP has worse incontinence reported with regards to pads per day and worse Sexual Bother scores, while ADT+ XRT has worse nocturia and bloody stools.

So from this data, it seems to suggest that ADT+RT is equivalent to RP. Then why do Urologists perform RP at all? Are the bloody stools from XRT so bad that physicians recommend surgery instead?

Thanks

I work with some excellent urologists who do the biopsy, review all options from active survellience to surgery and then refer all patients for a radiation oncology consult and let them make an informed, individual decision.

There are others who do the biopsy and schedule surgery as if it’s the only option. If patients ask about active survellience they simply scare them into getting treatment and if the patient asks about radiation they say anything from radiation is great but it’s not a good option for them (may or may not be true) or radiation is terrible (just to get them to undergo surgery) and that’s that case closed.

In almost every other cancer (gyn being the other that’s like urology) somebody does the biopsy (GI, Pulm, IR, etc) and then referrals are made to the various oncologists but in urology and gyn the person who diagnoses also treats so can easily convince the patient to get their therapy without the patient even hearing about other options, which are often equivocal with individual pros and cons but sometimes straight up superior.

 

[FistLength]

I work with some excellent urologists who do the biopsy, review all options from active survellience to surgery and then refer all patients for a radiation oncology consult and let them make an informed, individual decision.

There are others who do the biopsy and schedule surgery as if it’s the only option. If patients ask about active survellience they simply scare them into getting treatment and if the patient asks about radiation they say anything from radiation is great but it’s not a good option for them or radiation is terrible that’s that case closed.

In almost every other cancer (gyn being the other that’s like urology) somebody does the biopsy (GI, Pulm, IR, etc) and then referrals are made to the various oncologists but in urology and gyn the person who diagnoses also treats so can easily convince the patient to get their therapy without the patient even hearing about other options, which are often equivocal with individual pros and cons but sometimes straight up superior.

bingo
Many times they convince patients it's not right for them and don't even give a referral to the patient to see a rad onc.
Isn't it funny when a urologist group buys a linear accelerator and hires a rad onc then they are very pro radiation all of a sudden? But, of course, not brachytherapy, and certainly not hypofractionation.
Not surprising NEJM paper

 

[vpras1234]

bingo
Many times they convince patients it's not right for them and don't even give a referral to the patient to see a rad onc.
Isn't it funny when a urologist group buys a linear accelerator and hires a rad onc then they are very pro radiation all of a sudden? But, of course, not brachytherapy, and certainly not hypofractionation.

Thats horrifying. I’m surprised that isn’t illegal

 

[CherryRedDracul]

Thats horrifying. I’m surprised that isn’t illegal

Wait till you delve deeper into the dark underbelly of medicine/surgery.

 

[Radiated_GuineaPig]

In a related point, in high risk prostate cancer there is no level 1 evidence that prostatectomy does an ounce of good. Radiation has 2 randomized phase III trials that show superiority over hormone therapy with respect to overall survival, but plenty of urologists hold prostatectomy as substantially superior to radiation in this population. NCCN has EBRT and EBRT+brachy boost as level 1... prostatectomy is level IIa at best.

 

[Haybrant]

Thats horrifying. I’m surprised that isn’t illegal

Always interesting to see when the curtains start to rise. I’ve said it many times, if the public really understood what was going on in medicine it would dwarf the credit financial scandal a hundred times over. I will say though that prostate recurrences after RT that progress to Become a big local issue (young patients) really really sucks.

Obviously though you can’t use protect to compare surgery and RT. One could argue that surgery outcomes powered inferior RT.

 

[Palex80]

Some dudes can't/don't want to put up with 8 weeks of radiation treatment and decide that getting it done in a day is worth the side effects

Or their urologist convinces them Radiation isnt as great as it sounds so they never see a radiation oncologist

1. Noone needs 8 weeks of radiation treatment. Not any more.
4 weeks of hypofractionated RT will suffice for the vast majority of patients. A sizable portion of the patient can also be treated within a week with stereotactic highly-hypofractionated schedules and stereotactic setup.

2. "Done in a day" is quite illusional. No patient leaves the hospital one day after RP. Most stay roughly a week or so and many of them still have troubles at home after surgery.

3. The main point is who manages the patient and how well the patient is informed of possible alternatives.

 

[Palex80]

For real. The 10 year disease progression free survival is pretty impressive for AS

Roughly half of the AS patients had treatment "down the road". This is just an intention to treat analysis not an as treated analysis.

 

[Palex80]

We should pity our colleagues in the surgical oncological disciplines. In the past years they have taken hits after hits, limiting the patients they operate on, while only a few new indications popped up. Gaze at what happened 15 years ago and you'll see my point...

Urologists:
RT has become a very good alternative to RP for prostate cancer. Patients are more informed about alternatives (Thank you internet for that! Think of how few elderly patients had internet access 15 years ago.)
Nephrectomy has been killed off as s.o.c. for metastatic renal cell cancer or has at least come under severe fire in the past year.
Immunotherapy is working very well in bladder cancer. It is probably a matter of time until someone runs a trial combining it with RT and chemo and showing excellent outcomes.

Thoracic surgeons:
SBRT is not quite there yet as we would like it to. Minimal invasive surgery (VATS) has made surgery less troublesome. But no worries... Trials are running and I doubt that SBRT will fare worse than VATS in stage I NSCLC.
In Stage III NSCLC I am seeing first signs of oncologists being interested in going for primary radiochemotherapy rather than induction CT followed by surgery due to PACIFIC.

Dermatologists / General Surgeons:
Complete lymphadenectomy for sentinel node positive melanoma is no longer recommended.

Neurosurgeons:
Growing evidence of radiosurgery and proof that it works with multiple lesions too has also led to less craniotomies for metastasecotomies being performed (at least in my department).

Colorectal surgeons:
Watch and wait after RCT for low rectal cancer which would require non-sphincter conserving surgery is becoming more and more an option. I've managed a few patients like this and haven't seen a recurrence (yet).
I hear there are trials being run for early rectal cancer too with RT alone +/- mucosectomy. No more major surgery for cT1-2 rectal cancer in 5 years from now perhaps?

Breast surgeons:
Radical lymphadenectomy is being reduced step by step for most patients, several trials completed and published and more on the way.

Of course we have "lost" some RT indications too... Think of Hodgkin's or seminoma. But still... I don't think the surgeons like what we are doing to them... 🙂

 

[nimbus]

I know a urologist, a family member, who stopped doing RP all together after he took an ownership stake in an RT Center.

 

[scarbrtj]

Thats horrifying. I’m surprised that isn’t illegal

*disclaimer: I do not own "IMRT services," I am not a partner with a urologist, I do not directly benefit from referral etc.

Some things I think most radiation oncologists could agree on:
1) Whenever a prostate is external-beam irradiated, it should be IMRT. (Probably not protons but that's another subject.)
2) If the prostatectomy and seed brachy vanished tomorrow and all we had was IMRT (SBRT=SABR=Cyberknife=IMRT), I do not think we would think this was a medical tragedy: IMRT is that good.
3) The shift from older teletherapy means to linear accelerators (1960s-1980s) was not accompanied by near the amount of silly rancor, or good supporting data, that the shift from non-IMRT to IMRT was (2000 to pre-2010).

If you never had a car and you buy a car, your car use goes way up. Radiation oncologists who start working in proton centers ALL OF A SUDDEN start using protons way more often; they love it! You can attach a nefarious motive to anything, especially when it comes to money. Take money out of it: is IMRT good for prostate? Yes. I grew up in the pre-IMRT days; in that time period ~2005-2010 in the NEJM article, IMRT use was EXPLODING across America and the world in every disease site imaginable (first IMRT treatments in academic centers occurred late 90's and first IMRT treatments in community practices around 2001 and 2002). It didn't explode because of money (although money greased the wheels), it exploded because after you treated a few patients with IMRT it was, like, whoa... patients do better. The "bloody stools" you mentioned were essentially abolished by IMRT IMHO. (In addition, I think the cystectomy should go away too; we can argue that, but it's my opinion and if I wanted to treat ALL bladder cancer with radiation I can make an argument for it. So if you're a urologist, and you want to be a full-service urological facility... why not add radiation, and a good rad onc, for the benefit of your patients?) You can certainly make a correct argument that if a urologist owns "IMRT services" more $ goes in urologists' pockets for prostate CA tx; but money's gotta go in somebody's pocket for a prostate CA tx, and it can be more $ for surgery than IMRT.

 

[Raryn]

Or each urologist assures their patient that their outcomes are much better.
Or the urologist has been doing RPs for 30 years and hasn't adopted the XRT methods.
Gotta say, though. After a year or so of prostate cancer research I'm an active surveillance fan myself...

Based on the current state of the evidence, if I was in the right age group, I would decline all screening for prostate cancer. If something was found incidentally, I would decline all treatment. I much prefer my quality of life to decreasing the tiny chance that prostate cancer actually spreads and kills me.

That said, I fully anticipate that by the time I hit my 50s and up, we'll have targeted molecular therapies that will cause significantly less morbidity than current treatments.

Before I get accused of just being biased because it isn't my own field - Thyroid cancer evidence is trending the same direction. I routinely tell my patients to discuss the minimum necessary surgery with their surgeons - hemithyroidectomy vs total in addition to often deferring radioactive iodine, opting not to do long-term TSH suppression in low risk disease, etc. The data isn't 100% there regarding active surveillance yet, but there's one paper from Japan (Ito et al) that shows it as a viable option for a number of thyroid cancers, and ongoing studies with Tuttle at MSK. The other problem we run into is that many patients are diagnosed with thyroid cancer at much younger ages, so active surveillance for a 30-year old is a different prospect than for a 70 year old.

 

[Haybrant]

Based on the current state of the evidence, if I was in the right age group, I would decline all screening for prostate cancer. If something was found incidentally, I would decline all treatment. I much prefer my quality of life to decreasing the tiny chance that prostate cancer actually spreads and kills me.

That said, I fully anticipate that by the time I hit my 50s and up, we'll have targeted molecular therapies that will cause significantly less morbidity than current treatments.

Before I get accused of just being biased because it isn't my own field - Thyroid cancer evidence is trending the same direction. I routinely tell my patients to discuss the minimum necessary surgery with their surgeons - hemithyroidectomy vs total in addition to often deferring radioactive iodine, opting not to do long-term TSH suppression in low risk disease, etc. The data isn't 100% there regarding active surveillance yet, but there's one paper from Japan (Ito et al) that shows it as a viable option for a number of thyroid cancers, and ongoing studies with Tuttle at MSK. The other problem we run into is that many patients are diagnosed with thyroid cancer at much younger ages, so active surveillance for a 30-year old is a different prospect than for a 70 year old.

Only responding to this bc if you take care of patients You can’t take this tact bc you’re misguided, It’s not the screening that causes morbidity. I’ll definetly get the screening, it’s the treatment that does. The cancer won’t kill you, but you’ll live with it for a decade until you die an excruitiating death. We all know protect had a trend to increased mets in the no treatment arm. At 15 yrs it’s likely that will be stat significant.

 

[evilbooyaa]

Are there any other head to head RCTs for Radiation vs surgery?

No. Your analysis of the ProtecT trial is correct. The short answer is that some patients have the thought of "tumor is bad, cut the tumor out", or can be thought to think like that from the urologists. Urologists do the initial biopsy 100% of the time, and can offer a definitive treatment without involving any more physicians.

Otherwise, agree with the rest of the posts here. Palex is european, so hypofractionation (4 weeks instead of standard 8-9 weeks of daily treatment) is more common there, as they aren't fee for service. In the US, utilization of hypofractionated RT is very low (but will likely start increasing given recently published guidelines on hypofractionated RT)

Given the strong rad onc response in this thread, I'll invite some of our urology colleagues to respond to give their reasons and defend their specialty's decisions. Given that this topic of discussion has a strong preponderance to go off the rails and full dumpster fire (and given that it's in allopathic) I will pre-emptively remind all to keep discussions professional.

@cpants @DoctwoB

As an aside, the best (for a patient) clinics are the ones where both a urologist and radiation oncologist meet the patient before a definitive treatment decision is made. Given that surgeons gonna surgeon and rad oncs gonna radiate, this doesn't happen as oftenly as we would all like.

Once urologists own a linac (known as a urorads center) then they frequently love doing IMRT (a type of radiation planning that gets reimbursed at higher rates) for prostate. Financial incentive, generally speaking, is a consideration amongst many doctors, including both urologists and radiation oncologists.

NCCN guidelines are 50% urologists, so despite a lack of any randomized trials for high-risk prostate cancer, it's included as an option because "of course surgery is better than radiation. Just cut the tumor out!"

 

[Raryn]

Only responding to this bc if you take care of patients You can’t take this tact bc you’re misguided, It’s not the screening that causes morbidity. I’ll definetly get the screening, it’s the treatment that does. The cancer won’t kill you, but you’ll live with it for a decade until you die an excruitiating death. We all know protect had a trend to increased mets in the no treatment arm. At 15 yrs it’s likely that will be stat significant.

I counsel patients the evidence for screening improving outcomes is weak but still order a PSA if they want it. I don't even offer a DRE though - the evidence for that is so weak as to being nonexistant, no better than a coinflip. Even with experienced fingers.

I am also capable of making the fully informed decision myself that I would decline the screening.

 

[scarbrtj]

I counsel patients the evidence for screening improving outcomes is weak but still order a PSA if they want it. I don't even offer a DRE though - the evidence for that is so weak as to being nonexistant, no better than a coinflip. Even with experienced fingers.

I am also capable of making the fully informed decision myself that I would decline the screening.

1) Screening should not just be PSA now.
2) The vast majority of prostate CA patients I treat are on the golf course playing 18 on the last day of tx; pretty good QOL (any rectal toxicities <3% incidence, 0% incontinence rates) with tx's nowadays that won't be substantially better "because immuno" or something newer.
3) Prostate cancer does kill a ton of people believe it or not, and increasing death rates correlate with screening cessation; hand-waving acknowledged. Prostate cancer deaths dropped by 37% in the PSA era in the 1990's, the biggest drop in cancer death rates of any sort in the history of recorded medicine. And still, as you show, it's controversial.

 

[Donald Juan]

While nocturia and bloody stools sound relatively benign on a study, it doesn't really shed light on what radiation cystitis and proctitis really represent in a patient. They are typically in chronic pain and come to the ED frequently. Of course the rad onc doctors don't think much of this because the ED doesn't call them to come manage these patients. And when they have complications from radiation you now have an irradiated pelvis that is harder to place things like prosthetics or manage with other surgeries.

As far as survival to 10 years, of course it is similar. Prostate cancer is a slow growing cancer. You shouldn't even screen a patient if you expect their life expectancy to be less than 10 years, so any study looking at survival in prostate cancer patients needs to go out further. We don't treat early prostate cancer to keep patients alive only 10 years.

 

[Donald Juan]

No patient leaves the hospital one day after RP. Most stay roughly a week or so and many of them still have troubles at home after surgery.

I don't know what your urologists are doing if their patients don't leave after 1 day and stay for a week. Medicare even classifies it as an outpatient procedure and is pushing surgeons to send their RPs home same day, although the only people I know doing that operate a concierge service where a nurse goes to see the patients on POD1 at their hotel. Of the rest of us that don't have nice concierge services, 95% of prostatectomy patients go home POD1.

 

[scarbrtj]

t doesn't really shed light on what radiation cystitis and proctitis really represent in a patient. They are typically in chronic pain and come to the ED frequently.

Like the surgeon who's keeping RP patients in the hospital for a week, the rad onc who is having >1% rates of patients coming to ED with cystitis/proctitis is doing it wrong circa 2018. I published a retrospective analysis of modern IM-IGRT for prostate ca in the early days of the tech on ~1000 patients and we had zero incidents of patients having "emergent" cystitis/proctitis. Below, a typical radiation dose distribution (color=50% ie clinically significant prescription dose and higher); note the "whole pelvis" is not all irradiated either (this is a low-risk prostate patient).

 

[DoctwoB]

I don’t have great data to back it up, but I can tell you that at my institution hematuria or symptoms related to radiation cystitis is one of the most common consults we get in Urology. Sometimes it’s minor and self limiting, sometimes it’s life changing. I’ve seen 3 fatalities due to radiation cystitis (refractory hematuria-> bladder perf-> death or CMO), many patients who needed simple cystectomies, etc. FWIW in residency I only saw one fatality from prostatectomy (post op PE). I do believe that it is vastly under reported as many of these patients are years or even decades post the RT and the radiation oncologists are never called so remain blissfully unaware as they show up as no toxicity during trials.

Maybe if rad oncs spent their call nights shoving in 24 French garden hose hematuria catheters and irrigating clots out of radiated bladders they would have a different view. I’ve done this quite literally hundreds of times. Obviously there is a selection bias (I don’t see the many patients who got radiated and did great) but pretending that prostate xrt is benign if there is minimal acute toxicity is folly.

All that said, I agree that prostate cancer patients deserve to hear all options from an expert in said option, meaning see both urology and rad onc.

 

[scarbrtj]

I don’t have great data to back it up, but I can tell you that at my institution hematuria or symptoms related to radiation cystitis is one of the most common consults we get in Urology. Sometimes it’s minor and self limiting, sometimes it’s life changing. I’ve seen 3 fatalities due to radiation cystitis (refractory hematuria-> bladder perf-> death or CMO), many patients who needed simple cystectomies, etc.

Clearly I'm a rad onc, and clearly people have their preconceived notions on this, but it's malpractice and not a normal toxicity to have fatal cystitis from prostate XRT. When we intentionally irradiate the entire bladder, long-term bladder function has been shown to be great. When we do modern image-guided intensity modulated prostate XRT, we irradiate the tiniest smidgen (scientific term) of bladder right at the prostate base and it's nigh impossible to get a bad radiation cystitis from that. Or at the very least "life-changing" cystitis should be a fraction of what it is for intentional total bladder XRT (and it's already very, very low in intentional total bladder XRT). In the "old days," yes; nowadays, it should not be happening. (Although 'tis true: you can never get a radiation cystitis from a prostatectomy.)

 

[mistafab]

Clearly there is a turf war going on here.