Prostate health

[evilbooyaa]

I'd say most of my HR patients are from Urologists who do TRUS/Bx but not RP, and I'd say 50% of those I see would be candidates for RP. Not 100% given anesthesia and anticoag issues, but not zero.

I still wonder why we are not demostrating OS, metastatic-free survival improvement, or decreased need for hormones.

Well ASCENDE-RT is trying for the first 2, albeit as secondary endpoints. Maybe under-powered for anything besides PFS. Maybe patients eligible for brachy will have less competing mortality risks compared to those not considered brachy candidates.

Both arms of ASCENDE-RT got 1 year of ADT (one of the 'criticisms' that EBRT arm didn't get 1.5-2 years). Thought I had seen an analysis where BT arm got 1 year while EBRT got 2... maybe the Kishan multi-institutional retrospective analysis?

In regards to above - YES. Much prefer the control of HDR compared to LDR. Needle too close to urethra? That's OK, don't load it at those positions. HDR for boost was standard where I trained. We still offered LDR, but it didn't make sense to LDR for boost. LDR for monotherapy was more common, although a number of patients were willing to accept 2-fraction HDR for monotherapy as well.

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[MegaVoltagePhoton]

So call me biased because I do brachy for gyn, and I like brachy. But i think people are being a bit unfair here. the benefit in control over in 0126 was without ADT to muddle things, in a much lower risk group of people. in ascende and the big retrospective studies, it was unfav int and high risk with 12 months of adt for everyone. to show a benefit in bcr there is proportionately bigger than in 0126.


toxicity is what it is an i absolutely tell all my prostate patients (which is lower now because a bunch are doing SBRT) that GU toxicity WILL be worse, but there may be benefits too. i do think LDR is worse than HDR having done both. brachy is also very easy to mess up and ascende was a multi-institutional study without IMRT and without great quality oversight in real time.

its just kind of funny. people on this board decry our specialty acting poorly and eating ourselves etc. but when theres evidence of a legit good treatment, even if it has toxicity, people crap all over it. we need to be honest but you need to cut both ways. you think if a surgery trial came out showing a benefit to extended dissection but with more toxicity that the surgeons would pile on about doing a dissection?

these things cut both ways.


but in any case i can see with my own eyes sbrt taking over for prostate. so i might end up sticking with gyn full time anyway (cue scar pointing out how full time that really is)

 

[metview]

You're right that's definitely a weakness, though if salvage XRT wasn't used optimally and surgery still did better that's a feather in the cap of surgery. And under or delayed utilization of salvage XRT is a known issue in the real world setting. And my point isn't to say that surgery is obviously superior, just that equipoise exists and it isn't unreasonable for Urologists to treat high risk patients with surgery (though they should be informed about the likelihood of needing salvage) any more then it is unreasonable to treat patients with XRT + brachy + ADT

My personal hope is that the pendulum is and will swing the other way on PSAs. ERSPC long term data shows the number needed to screen to save a life is down to the 500s, and the longest term cohorts with the least contamination (Rotterdam and Gothenborg) show NNS in the 200s. That is much better then the data for mammogram and colonoscopy, and a PSA is much easier/cheaper then both of them. So with a little luck (and better patient care) there will be more for all of us to treat.

The Kishan et al paper ( 10.1001/jama.2018.0587 ) showed that EBRT+BT+ADT > EBRT+ADT = RP. In the RP group, 9% received adjuvant RT and and 34% received salvage RT, so about 45% received some form of post-operative RT, which is in line with percentage who will require post-operative RT per this recent trial (adjuvant vs salvage RT, Redirecting). The EBRT+ADT performed just as well as the RP group. Therefore, you cannot really say that RP+XRT > EBRT+ADT. EBRT+ADT is perfectly reasonable for HR pts especially when compared to RP.

 

[FrostyHammer]

Never underestimate the ability of American Radiation Oncologists to hand wave away retrospective data showing surgical superiority

Imma just leave this here

Comparative Effectiveness of Radical Prostatectomy Versus External Beam Radiation Therapy Plus Brachytherapy in Patients with High-risk Localized Prostate Cancer - PubMed. PROTECT also with slighly lower rates of BPFS with surgery vs. XRT in intermed/high risk

TBF I am also aware of a retrospective study showing XRT + brachy did better then surgery. Equipoise exists.

I'm not sure where this idea of Urologists being cowboys for treating high risk disease with surgery comes from. Some patients are just better candidates for surgery, especially those with pre-existing severe LUTS. I'd argue the bigger cowboys are the Radoncs treating high risk without brachy boost. Data (albeit poor quality data subject to bias) suggests outcomes are superior vs. XRT alone and equivalent to XRT + Brachy. All my high risk patients (all patients actually) are shown nomograms and are well aware of the risk of needing salvage XRT and in very high risk patients I tell them that it is multi-modal therapy.

I get your point, but don't deny that >90% of surgery vs nonsurgery (or RT) retrospective papers show superiority of surgery. It could be >97% more likely. It is so sad to see surgeons believing that stuff because the vast majority do not know how to critically evaluate and analyze the literature. They have no idea about "confounding by operability status" type biases, or other such biases that cause those pro-surgery findings. Retrospective data are good for certain circumstances, but this is not one of them. If you believe in higher quality of evidence, perhaps you can tell me about what ProtecT showed about RT vs surgery and the separate ProtecT publication detailing the QOL/PROs of RT vs surgery. Nearly all urologists I know pay so much attention to the pro-surgery retrospective papers and conveniently choose to ignore the randomized studies...what can I say...

And also, if you believe in brachy boost, I would go back and read ASCENDE-RT and really critically delve into it. Do you think that if the 1 year of ADT in that trial was actually 1.5-3 years of ADT, that the borderline p value in the high-risk cohort would have become significant? I'll put it to you this way: for a large randomized trial like that to be published in the Red Journal (as compared to JAMA journals, JCO, Lancet journals, etc.) is indicative of something fundamentally fishy...

 

[MegaVoltagePhoton]

I get your point, but don't deny that >90% of surgery vs nonsurgery (or RT) retrospective papers show superiority of surgery. It could be >97% more likely. It is so sad to see surgeons believing that stuff because the vast majority do not know how to critically evaluate and analyze the literature. They have no idea about "confounding by operability status" type biases, or other such biases that cause those pro-surgery findings. Retrospective data are good for certain circumstances, but this is not one of them. If you believe in higher quality of evidence, perhaps you can tell me about what ProtecT showed about RT vs surgery and the separate ProtecT publication detailing the QOL/PROs of RT vs surgery. Nearly all urologists I know pay so much attention to the pro-surgery retrospective papers and conveniently choose to ignore the randomized studies...what can I say...

And also, if you believe in brachy boost, I would go back and read ASCENDE-RT and really critically delve into it. Do you think that if the 1 year of ADT in that trial was actually 1.5-3 years of ADT, that the borderline p value in the high-risk cohort would have become significant? I'll put it to you this way: for a large randomized trial like that to be published in the Red Journal (as compared to JAMA journals, JCO, Lancet journals, etc.) is indicative of something fundamentally fishy...

the point about journals would make sense if there were not brachy boost vs RP and EBRT papers in both JAMA and JCO even if both were retrospective.

 

[seper]

the point about journals would make sense if there were not brachy boost vs RP and EBRT papers in both JAMA and JCO even if both were retrospective.

Red Journal publishing this is a red flag, without doubt

 

[ramsesthenice]

Again, this is coming from someone who wants to believe ASCENDE and offers it as a therapy. But something else that bothers me about the trial is I there is no good reason to explain the magnitude of the results. BT boost is essentially dose escalation so by extension you predict it should offer better in -gland control which might translate into better biochemical control. But knowing the natural history of prostate cancer, how many men with unfavorable disease experience isolated in gland recurrences after RT and ADT? I’m not sure there is a good answer to this but they are not all that common. You could invoke the notion that it kills the cancer faster and prevents distant spread but how likely is that in the setting of concurrent and adjuvant ADT? In the absence of radiographic or pathological evidence of better in gland control with BT boost I have really struggled to come up with a convincing reason why combo therapy should reduce biochemical failures as much as it appeared to in the trial. Understanding why something happens is obviously not a pre-req for it being real but it does and should send up flags when results look too good to be true.

 

[DoctwoB]

Again, this is coming from someone who wants to believe ASCENDE and offers it as a therapy. But something else that bothers me about the trial is I there is no good reason to explain the magnitude of the results. BT boost is essentially dose escalation so by extension you predict it should offer better in -gland control which might translate into better biochemical control. But knowing the natural history of prostate cancer, how many men with unfavorable disease experience isolated in gland recurrences after RT and ADT? I’m not sure there is a good answer to this but they are not all that common. You could invoke the notion that it kills the cancer faster and prevents distant spread but how likely is that in the setting of concurrent and adjuvant ADT? In the absence of radiographic or pathological evidence of better in gland control with BT boost I have really struggled to come up with a convincing reason why combo therapy should reduce biochemical failures as much as it appeared to in the trial. Understanding why something happens is obviously not a pre-req for it being real but it does and should send up flags when results look too good to be true.

I don’t have the numbers in front of me but believe that is precisely the reason; that boost provides better local control. Why do I believe it? Because of PSMA BCR data showing about 1/3 to half of BCRs after XRT are due to failure in the prostate IIRC (as opposed to surgery which has lower fossa recurrence (<10%, more nodal failure)

 

[ramsesthenice]

I don’t have the numbers in front of me but believe that is precisely the reason; that boost provides better local control. Why do I believe it? Because of PSMA BCR data showing about 1/3 to half of BCRs after XRT are due to failure in the prostate IIRC (as opposed to surgery which has lower fossa recurrence (<10%, more nodal failure)

Please share said data. Your post RP data sounds particularly questionable. If true, salvage RT would cease to have existed along time ago.

 

[Mandelin Rain]

Via nomogram, the chance of successful salvage of a psa 20, Gleason 8, negative margins with + ECE and - SVI who went undetectable after RP and rose to 0.2 prior to salvage is........ 50% without ADT.


This is because >50% have failed in the prostate bed. Pretty much confirms what you see in clinical practice. Undectable post prostatectomy psa, now rising = 50-75% chance of successful salvage with bed XRT because that’s where the cancer is.

<10%? Get out of here with that nonsense.

Now the guys I’ve seen with psa 80 and Gleason 9 disease who weren’t staged and come in with a post prostatectomy psa of 120.... I hold less hope for.

 

[ramsesthenice]

I don’t have the numbers in front of me but believe that is precisely the reason; that boost provides better local control. Why do I believe it? Because of PSMA BCR data showing about 1/3 to half of BCRs after XRT are due to failure in the prostate IIRC (as opposed to surgery which has lower fossa recurrence (<10%, more nodal failure)

Hruby G, Eade T, Kneebone A et al. Delineating biochemical failure with 68Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer. Radiother Oncol 2017;122(1):99–102

17% isolated local failures post RT

I will give you that some of the numbers (post RT) appear higher than I would have expected but I can’t find any studies showing <25% failure in the prostatic fossa (with most being higher).

 

[Palex80]

I don’t have the numbers in front of me but believe that is precisely the reason; that boost provides better local control. Why do I believe it? Because of PSMA BCR data showing about 1/3 to half of BCRs after XRT are due to failure in the prostate IIRC (as opposed to surgery which has lower fossa recurrence (<10%, more nodal failure)

Oh my...

May I please quote to this wonderful paper?

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy - PubMed

Men with high-Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis. Among men with high-Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical st …

pubmed.ncbi.nlm.nih.gov

The lower curve is the BFS for high-risk patients post surgery without adjuvant treatment.
"high-risk" defined as GS8-10 or pT3b or pN1.

4% at 10 years...

 

[ramsesthenice]

I don’t have the numbers in front of me but believe that is precisely the reason; that boost provides better local control. Why do I believe it? Because of PSMA BCR data showing about 1/3 to half of BCRs after XRT are due to failure in the prostate IIRC (as opposed to surgery which has lower fossa recurrence (<10%, more nodal failure)

Also, let’s clarify my point. We are on the same page about why combination therapy could be better (and probably is). I do not question the overall message of ASCENDE. I better not since I use it as a treatment LOL. The question for me with ASCENDE is why it’s so much better. Let’s assume 1/3rd of guys with any failure had failures in the prostate gland. In the trial they saw a 50% reduction in biochemical failures With combination therapy. So even if BT provided 100% local tumor control that still wouldn’t get you to a 50% reduction in all failures.

Why does this (potentially) matter? Because the magnitude of benefit is relevant when you are weighing against added toxicity and trying to decide what to do. As I eluded to earlier, I think the reason tox was so high on trial was how they did it (LDR implants) and there is a way around that.

 

[Chartreuse Wombat]

Hruby G, Eade T, Kneebone A et al. Delineating biochemical failure with 68Ga-PSMA-PET following definitive external beam radiation treatment for prostate cancer. Radiother Oncol 2017;122(1):99–102

17% isolated local failures post RT

I will give you that some of the numbers (post RT) appear higher than I would have expected but I can’t find any studies showing <25% failure in the prostatic fossa (with most being higher).

Eight (17%) had an isolated LR, which represents 2% of patients managed with definitive EBRT and followed for at least 2years.

In the context of why is ASCENDE brachy boost better the 2% is more germane. There is something strange about ASCENDE-RT. I offer this as an option in healthy men with high risk disease (no T3s though since they were excluded)

 

[evilbooyaa]

I don’t have the numbers in front of me but believe that is precisely the reason; that boost provides better local control. Why do I believe it? Because of PSMA BCR data showing about 1/3 to half of BCRs after XRT are due to failure in the prostate IIRC (as opposed to surgery which has lower fossa recurrence (<10%, more nodal failure)

In regards to bolded, duuuuuuuuuuuuuude, what?? If your statement was true treating fossa alone would NOT work. From RTOG 0534(SPPORT), the rate of prostate fossa RT alone (without any hormones, without coverage of pelvic LNs) successful salvage in patients with documented relapse after surgery was about 66%. C'mon man. That means 2 out of 3 patients in that arm had a fossa only recurrence if RT did anything at all.

 

[DoctwoB]

Via nomogram, the chance of successful salvage of a psa 20, Gleason 8, negative margins with + ECE and - SVI who went undetectable after RP and rose to 0.2 prior to salvage is........ 50% without ADT.


This is because >50% have failed in the prostate bed. Pretty much confirms what you see in clinical practice. Undectable post prostatectomy psa, now rising = 50-75% chance of successful salvage with bed XRT because that’s where the cancer is.

<10%? Get out of here with that nonsense.

Now the guys I’ve seen with psa 80 and Gleason 9 disease who weren’t staged and come in with a post prostatectomy psa of 120.... I hold less hope for.

You’re right that the data begs the question why does salvage work if there isn’t local failure?

I think for two reasons. One is at the PSAs we’re salvaging at even PSMA is frequently non diagnostic so it likely is an underestimate of local failure (just like PSMA after XRT or using BS Phoenix criteria for a BCR). The second is that a lot of failure is in the nodes which would are often covered In salvage.

 

[MegaVoltagePhoton]

You’re right that the data begs the question why does salvage work if there isn’t local failure?

I think for two reasons. One is at the PSAs we’re salvaging at even PSMA is frequently non diagnostic so it likely is an underestimate of local failure (just like PSMA after XRT or using BS Phoenix criteria for a BCR). The second is that a lot of failure is in the nodes which would are often covered In salvage.

no they are challenging that the data you quote are reliable and/or exist. Nodes are not routinely covered at all, either.

 

[DoctwoB]

Oh my...

May I please quote to this wonderful paper?

Preoperative characteristics of high-Gleason disease predictive of favourable pathological and clinical outcomes at radical prostatectomy - PubMed

Men with high-Gleason sum at biopsy are at high risk for biochemical recurrence, metastasis and death after RP; men with high Gleason sum and advanced pathological stage (pT3b or N1) have the worst prognosis. Among men with high-Gleason sum at biopsy, a PSA concentration of >10 ng/mL, clinical st …

pubmed.ncbi.nlm.nih.gov

View attachment 319481

The lower curve is the BFS for high-risk patients post surgery without adjuvant treatment.
"high-risk" defined as GS8-10 or pT3b or pN1.

4% at 10 years...

Or you can look at the randomized Messing trial data and see 30-35% at 10 years for pN1-3. Which study you cite matters.

Personally I use the MSKCC nomograms which will show a BCR free survival at 5 years of 30-60% for most high risk patients, and 10-40% at 10 years. At which point many of our patients will be dead from competing risks despite our best efforts at guessing survival.

It’s all in the counseling. Would you rather have XRT and brachy and ADT right now or surgery right now and likely XRT several years down the road. Patients can reasonably decide that either approach is right for them.

 

[DoctwoB]

no they are challenging that the data you quote are reliable and/or exist. Nodes are not routinely covered at all, either.

After XRT. The use of 68Ga-PET/CT PSMA to determine patterns of disease for biochemically recurrent prostate cancer following primary radiotherapy
57% local failure rate

After surgery

Location of Recurrence by Gallium-68 PSMA-11 PET Scan in Prostate Cancer Patients Eligible for Salvage Radiotherapy - PubMed

The 68Ga-PSMA-11 PET detects disease in a majority of patients with PSA ≤2.0 following RP. Nearly one-third of men had PSMA-avid disease that would be missed by standard radiation fields. This imaging modality may dramatically impact the design and use of post-RP salvage radiotherapy.

pubmed.ncbi.nlm.nih.gov

12% local failure rate.

 

[MegaVoltagePhoton]

you are not considering the detection rate of PSMA. In your first study (post RP) the median PSA was 0.4. In the second (post RT) it was 3.6. Now look at the JAMA Oncology Fendler paper and tell me what the detection rates of PSMA are, by PSA. Keep in mind, these are all patients who recurred. So in population with a 10 fold higher PSA, there were more local recurrences? Ok, great...Many of the radiation patients in your study even had brachytherapy and the nadir PSA should be close to 0.2 or less. Second the post RT paper included doses as low as 60 and we have no information on adt use which is also important for disease control.

 

[Palex80]

Or you can look at the randomized Messing trial data and see 30-35% at 10 years for pN1-3. Which study you cite matters.

Of course it does. But who would you rather trust? Baltimore or one of the worst trials ever performed?

Personally I use the MSKCC nomograms which will show a BCR free survival at 5 years of 30-60% for most high risk patients, and 10-40% at 10 years. At which point many of our patients will be dead from competing risks despite our best efforts at guessing survival.

30-60% at 5 years and 10-40% at 10 years for high risk? That is very optimistic.

Here's what comes up for a typical high-risk pT3a R1 GS 4+4=8 cancer in the MSKCC nomogram.
5 years 16%, 10 years 9%.

I didn't even put in pT3b or a higher GS. I didn't even put in pN1. My PSA was <20 ng/ml.

If you are telling your patients with high-risk cancer, that their chance of freedom from PSA-recurrence at 10 years is 40% you are clearly lying to them.
I even put in the least high-risk I could in the nomogram and it still turned out well below 40%.

And the most misleading of all and I am sorry that I am calling it misleading, but that's what it is in my view, is giving such wide ranges of estimates to the patients. "10-40%" means that most patients will hear the 40% and forget about the 10%.
It's like the lottery.
"If you are lucky, you can win 10 or up to 1.000.000 dollars if you buy a ticket" will make more people buy a ticket than "If you win, you will likely receive 10 dollars and there's a 0.000001% chance of you getting 1.000.000 dollars."

It’s all in the counseling. Would you rather have XRT and brachy and ADT right now or surgery right now and likely XRT several years down the road.

The more therapy you get, the higher the chance for side-effects. If the chance of you needing early postoperative XRT is well above 50%, there is little reason to opt for surgery from an oncologic point of view.
Counseling is clearly important and in my view the best counseling results when the urologist and the radiation oncologist talk with the patient together. It's something we do in our clinic very often and helps to get the facts straight.

 

[evilbooyaa]

You’re right that the data begs the question why does salvage work if there isn’t local failure?

I think for two reasons. One is at the PSAs we’re salvaging at even PSMA is frequently non diagnostic so it likely is an underestimate of local failure (just like PSMA after XRT or using BS Phoenix criteria for a BCR). The second is that a lot of failure is in the nodes which would are often covered In salvage.

I showed you a picture of a ~60% control rate with salvage prostate fossa RT alone. You are sticking to dogma (bolded) that is not accurately reflected in the literature. Prior to 0534 presentation, coverage of LNs in salvage setting was very, very patient and physician dependent. Many a rad onc wouldn't cover LNs (in salvage setting) unless patients were N+. 0534 was practice changing in that regard for many.

@Palex80 he may be using the pre-radical prostatectomy nomogram (since he would be counseling patients before surgery). A 75yo with G4+4=8, PSA of 12, with 25% cores positive (5 pos, 15 neg) with cT1c disease does give 5/10 year rates of bPFS of 49% and 34%.

While this is *barely* high-risk disease, I imagine that is the upper end of numbers DoctwoB is quoting. I do support his/her use of routinely checking MSKCC prior to surgery, and quoting that number to each individiual patient. Even in this low-risk patient, 50% chance of biochemical relapse at 5-years. Thus add on toxicity of salvage RT as well in 50% of patients.

Also, IDK what relevance of some random post-treatment PSMA scans with no stringent inclusion criteria was - agree with Mandelin Rain that post-RT nadir PSA mean of 3.6 is quite high.

Let's look at a randomized trial for high-risk patients. The below graph is figure 2C from ASCENDE-RT, which is the high-risk subgroup enrolled on that trial. Red is with BT boost, black is Dose escalated EBRT, both with 1 year of ADT. Even in the black arm, 5-year rate of bPFS was about 80%, and still at about 50% at 10-year. So seems like RT has higher rates of control compared to RP. Of course salvage after RP is generally easier and less toxic than salvage after RT, which is why OS will be the same between each treatment strategy, but this notion of 'RP patients recur less than RT patients' is patently false.

 

[DoctwoB]

Of course it does. But who would you rather trust? Baltimore or one of the worst trials ever performed?


30-60% at 5 years and 10-40% at 10 years for high risk? That is very optimistic.

Here's what comes up for a typical high-risk pT3a R1 GS 4+4=8 cancer in the MSKCC nomogram.
5 years 16%, 10 years 9%.

I didn't even put in pT3b or a higher GS. I didn't even put in pN1. My PSA was <20 ng/ml.

If you are telling your patients with high-risk cancer, that their chance of freedom from PSA-recurrence at 10 years is 40% you are clearly lying to them.
I even put in the least high-risk I could in the nomogram and it still turned out well below 40%.

And the most misleading of all and I am sorry that I am calling it misleading, but that's what it is in my view, is giving such wide ranges of estimates to the patients. "10-40%" means that most patients will hear the 40% and forget about the 10%.
It's like the lottery.
"If you are lucky, you can win 10 or up to 1.000.000 dollars if you buy a ticket" will make more people buy a ticket than "If you win, you will likely receive 10 dollars and there's a 0.000001% chance of you getting 1.000.000 dollars."



The more therapy you get, the higher the chance for side-effects. If the chance of you needing early postoperative XRT is well above 50%, there is little reason to opt for surgery from an oncologic point of view.
Counseling is clearly important and in my view the best counseling results when the urologist and the radiation oncologist talk with the patient together. It's something we do in our clinic very often and helps to get the facts straight.

Varying definitions of high risk. You did not choose the lowest forms of high risk, you chose R1 and T3b. A pT2 GG4 is high risk. a pT3a GG3 is high risk pathologically. A GG4 PSA <10, pT2 R0 has a 10 year BCR free survival of 50%. I tailor my counselling to the patient and give them more specific numbers, not "10-40%" I just used that as a range for what you might see with high risk, because there is a lot of variation.

Also, remember that a BCR has a variable, if any, effect on PCSM, especially if it occurs years after the RP. I also disagree that there is no time effect of treatment. If I ask 10 patients, what would you rather have, some QOL effecting treatment now or in 10 years, they will all say in 10 years. Finally if we go by the PROTECT data, the BC failure rate for intermediate and high risk disease was slightly lower in the surgery arm.

Lastly, one thing I never see Rad Oncs address is I would much rather progress after surgery (or surgery + salvage XRT) then after radiation. Why? Because my prostate is out and I will progress distally. If you fail locally after radiation (50% of radiation failures!), you are in a world of hurt after you progress through your ADT/novel hormonal agents.. Ongoing bleeding. Urinary retention. Foleys. Prostate embolization. Channel Turps leading to incontinence. Fistulas. The list goes on. Oh and who is most likely to ail like this? High risk patients. Same thing with bladder cancer. You will not see more miserable deaths then patients who die from bladder cancer who still have their bladder in.


Anyways, I'm sorry for sending this thread down the surgery vs. XRT rabbit hole. I'm not as anti-radiation as I sound, I think it's a good option for most and ideal option for some prostate cancer patients. I was just slightly triggered by the insinuations that Urologists shouldn't touch high risk patients. Also the Urology forum gets like 1 post/year so I was bored.

 

[evilbooyaa]

Varying definitions of high risk. You did not choose the lowest forms of high risk, you chose R1 and T3b. A pT2 GG4 is high risk. a pT3a GG3 is high risk pathologically. A GG4 PSA <10, pT2 R0 has a 10 year BCR free survival of 50%. I tailor my counselling to the patient and give them more specific numbers, not "10-40%" I just used that as a range for what you might see with high risk, because there is a lot of variation.

Also, remember that a BCR has a variable, if any, effect on PCSM, especially if it occurs years after the RP. I also disagree that there is no time effect of treatment. If I ask 10 patients, what would you rather have, some QOL effecting treatment now or in 10 years, they will all say in 10 years. Finally if we go by the PROTECT data, the BC failure rate for intermediate and high risk disease was slightly lower in the surgery arm.

Source?

In ProtecT, Surgery and RT both had improved clinical progression rates (https://www.nejm.org/doi/full/10.1056/NEJMoa1606220) compared to active surveillance, but there were no differences between the surgery and radiation arms.

I do not see any data on bPFS from ProtecT

 

[Palex80]

Varying definitions of high risk. You did not choose the lowest forms of high risk, you chose R1 and T3b.

I did not. Read my post. I chose pT3a and R1.

Now here's the challenge: Go back into that nomogram and show me 10% risk of biochemical-failure with a high-risk tumor post prostatectomy. Post it here as a screenshot.


Then I will post you a screenshot of 60% risk of biochemical failure so that we can debunk your 40% claim.

Finally if we go by the PROTECT data, the BC failure rate for intermediate and high risk disease was slightly lower in the surgery arm.

PROTECT practically did not include high-risk, there were 2% of patients with GS8-10 in PROTECT. Only a quarter of all patients were intermediate-risk actually.

Lastly, one thing I never see Rad Oncs address is I would much rather progress after surgery (or surgery + salvage XRT) then after radiation. Why? Because my prostate is out and I will progress distally. If you fail locally after radiation (50% of radiation failures!), you are in a world of hurt after you progress through your ADT/novel hormonal agents.. Ongoing bleeding. Urinary retention. Foleys. Prostate embolization. Channel Turps leading to incontinence. Fistulas. The list goes on. Oh and who is most likely to ail like this? High risk patients. Same thing with bladder cancer. You will not see more miserable deaths then patients who die from bladder cancer who still have their bladder in.

The well known "fairy-tale" of urologists. The problem is, you have failed to back it up with data.
We do not really know how many of patients treated with primary-RT alone will fail only locally and how bad their symptoms will be and if the problems and interventions you mention are merely a product of cognitive bias. One does tend to think of the "bad" cases more often than of all the other ones that never had any issues.
Data from STAMPEDE Arm H testing local radiotherapy on top of ADT for M1-disease, clearly show that the need for local treatment in men with M1 disease with or without ANY kind of local treatment to the prostate (STAMPEDE patients in Arm H were de-noco-metastatic) was around 97%. Only 3% of all patients required intervention for their never-locally-treated primary tumor, like a palliative TUR-P for instance.

I was just slightly triggered by the insinuations that Urologists shouldn't touch high risk patients. Also the Urology forum gets like 1 post/year so I was bored.

You can touch some of them, but not as many as you currently do.

 

[thecarbonionangle]

In med school, i almost did urology. I did a rotation with a famous one and was shocked at the lack of evidence based medicine. Overall, definitely one of the least evidence based field, lots of anecdotal data and retrospective reviews and ignoring higher quality data. Hence, i became a rad onc. Funny thing is rad onc is a dumpster fire now.

 

[medgator]

In med school, i almost did urology. I did a rotation with a famous one and was shocked at the lack of evidence based medicine. Overall, definitely one of the least evidence based field, lots of anecdotal data and retrospective reviews and ignoring higher quality data. Hence, i became a rad onc. Funny thing is rad onc is a dumpster fire now.

The antithesis of urology, job market wise

 

[scarbrtj]

Speaking of urologists... I was not aware that Varian is selling cryosurgery devices to the urologists now. (They're selling RFA equipment too.)

CryoCare CS | Varian

Cryoablation – Interventional Radiology

www.varian.com

 

[deleted941485]

The antithesis of urology, job market wise

You neglected the most basic rule of medicine. You will be punished for your good deeds. EBM just paints you into a corner.

 

[sloh]

Crab mentality, also known as crab theory or crabs in a bucket (also barrel, basket, or pot) mentality, is a way of thinking best described by the phrase "if I can't have it, neither can you." The metaphor is derived from a pattern of behavior noted in crabs when they are trapped in a bucket. While any one crab could easily escape, its efforts will be undermined by others, ensuring the group's collective demise.

 

[thecarbonionangle]

Crab mentality, also known as crab theory or crabs in a bucket (also barrel, basket, or pot) mentality, is a way of thinking best described by the phrase "if I can't have it, neither can you." The metaphor is derived from a pattern of behavior noted in crabs when they are trapped in a bucket. While any one crab could easily escape, its efforts will be undermined by others, ensuring the group's collective demise.

furthermore, some may say the field is in warming water, being boiled alive like crabs. Some do not even notice it!!!

 

[scarbrtj]

Crab mentality, also known as crab theory or crabs in a bucket (also barrel, basket, or pot) mentality, is a way of thinking best described by the phrase "if I can't have it, neither can you." The metaphor is derived from a pattern of behavior noted in crabs when they are trapped in a bucket. While any one crab could easily escape, its efforts will be undermined by others, ensuring the group's collective demise.

it all dovetails man!

 

[DoctwoB]

Jumping back in with clinical case. 50 yo M, GG1 on bx from outside urologist, cT1c, PSA 7. Elected for brachy monotherapy. Now new to me 2 years later, PSA dropped to 4, then jumped to mid 20s. Axumin PET/CT with multiple 2-3cm lymph nodes on external and common illiac chains, no uptake in the prostate, no other sites of disease. Going to discuss at tumor board this week.

Was thinking salvage LND and was considering biopsy of prostate to see if any residual disease. There are a decent number of case series of salvage LND after local therapy (XRT or prostatectomy) with reasonable biochemical control. I couldn't find any data on salvage XRT for clinical lymph node failure after brachy. I've seen whole pelvis XRT with boost to cN+ nodes, but if there are multiple and post brachy is that still feasible? Any role for combo of surgical LND + adjuvant XRT?

 

[Ray D. Ayshun]

Jumping back in with clinical case. 50 yo M, GG1 on bx from outside urologist, cT1c, PSA 7. Elected for brachy monotherapy. Now new to me 2 years later, PSA dropped to 4, then jumped to mid 20s. Axumin PET/CT with multiple 2-3cm lymph nodes on external and common illiac chains, no uptake in the prostate, no other sites of disease. Going to discuss at tumor board this week.

Was thinking salvage LND and was considering biopsy of prostate to see if any residual disease. There are a decent number of case series of salvage LND after local therapy (XRT or prostatectomy) with reasonable biochemical control. I couldn't find any data on salvage XRT for clinical lymph node failure after brachy. I've seen whole pelvis XRT with boost to cN+ nodes, but if there are multiple and post brachy is that still feasible? Any role for combo of surgical LND + adjuvant XRT?

Fwiw, an approach similar to what you mentioned from an RT POV could happen here with a simultaneous boost to gross disease. There are a number of dose/fractionation schemes that are possible, which would entail at least long-term ADT, though there are some hypofractionated things without adt that could be tried if the goal is simply to pause things for a bit. In a 50 yo, seems like going all out is warranted. Would not retreat the prostate. The biggest difference is he'll relapse sooner with surgery, thanks to the adt. I don't know much about a combined approach, but doesn't seem worthwhile.

 

[evilbooyaa]

Did patient have MRI prior to initial treatment confirming no lesions suspicious for higher Gleason disease?
If no uptake in prostate, would favor LN only salvage. Reasonable to do ADT + RT to LN basins with simultaneous boost to cN+, but lymph node dissection + adjuvant RT would be reasonable as well. I think control of LNs in prostate cancer, because boosting lymph nodes (especially external iliac ones) will be limited by bowel in proximity, may be better with surgery + RT.

 

[thecarbonionangle]

I’d have to look at the scan but as explained above, if very close to bowel which would be dificult to give a curative XRT dose, would favor surgery, radiation would still be an option in
The future. If no uptake in prostate would consider omitting it in XRT field. However you can also consider treating it. In regards to ADT, he should technically get it but if the nodes are treated or removed and theres no new sites in follow up scan, can consider observing and sparring him the ADT side effects as long as possible, which may be a concern in a likely sexually active younger guy like himself.

 

[Palex80]

The future. If no uptake in prostate would consider omitting it in XRT field. However you can also consider treating it. In regards to ADT, he should technically get it but if the nodes are treated or removed and theres no new sites in follow up scan, can consider observing and sparring him the ADT side effects as long as possible, which may be a concern in a likely sexually active younger guy like himself.

I would give the ADT on top of RT. There is good data pointing out that patients with resected pN1 disease after RPE do well if you combine ADT + RT as adjuvant treatment. He is 50 years old. Delivering full treatment now is his last chance for cure.

 

[scarbrtj]

Jumping back in with clinical case. 50 yo M, GG1 on bx from outside urologist, cT1c, PSA 7. Elected for brachy monotherapy. Now new to me 2 years later, PSA dropped to 4, then jumped to mid 20s. Axumin PET/CT with multiple 2-3cm lymph nodes on external and common illiac chains, no uptake in the prostate, no other sites of disease. Going to discuss at tumor board this week.

Was thinking salvage LND and was considering biopsy of prostate to see if any residual disease. There are a decent number of case series of salvage LND after local therapy (XRT or prostatectomy) with reasonable biochemical control. I couldn't find any data on salvage XRT for clinical lymph node failure after brachy. I've seen whole pelvis XRT with boost to cN+ nodes, but if there

I would give the ADT on top of RT. There is good data pointing out that patients with resected pN1 disease after RPE do well if you combine ADT + RT as adjuvant treatment. He is 50 years old. Delivering full treatment now is his last chance for cure.

anybody ‘round here seen a young fellow dx age 48 with CaP and soon recur with multiple positive large pelvic LNs get a treatment (package) and then go 10y disease free without treatment (that’s how I’d define cure).

 

[thecarbonionangle]

I would give the ADT on top of RT. There is good data pointing out that patients with resected pN1 disease after RPE do well if you combine ADT + RT as adjuvant treatment. He is 50 years old. Delivering full treatment now is his last chance for cure.

Absolutely but some of these patients are absolutely miserable with ADT. i think with PSMA we may eventually have data to treat those areas to delay need for ADT. The chance of controlling it with local treatment alone is not good

 

[DoctwoB]

Did patient have MRI prior to initial treatment confirming no lesions suspicious for higher Gleason disease?
If no uptake in prostate, would favor LN only salvage. Reasonable to do ADT + RT to LN basins with simultaneous boost to cN+, but lymph node dissection + adjuvant RT would be reasonable as well. I think control of LNs in prostate cancer, because boosting lymph nodes (especially external iliac ones) will be limited by bowel in proximity, may be better with surgery + RT.

No up front MRI, just got a standard 12 core biopsy. Given his age/health definitely favoring being aggressive with LND + adjuvant XRT +/- ADT, but will see what my local radoncs think of tumor board (maybe do a prostate biopsy before hand to ensure no residual disease, because if so would lean towards just XRT up front).

 

[ramsesthenice]

No up front MRI, just got a standard 12 core biopsy. Given his age/health definitely favoring being aggressive with LND + adjuvant XRT +/- ADT, but will see what my local radoncs think of tumor board (maybe do a prostate biopsy before hand to ensure no residual disease, because if so would lean towards just XRT up front).

Im not sure I see how the prostate biopsy will help you. Why would you be more or less inclined to do a PLND if you got a positive bx in the prostate? If the nodes are close to bowel and can’t be adequately addressed by RT the patient may still benefit from surgery. Also, I would imagine the false negative rate of random biopsies in this setting is pretty high. Not sure I would personally feel like negative bx of the prostate is all that helpful at convincing me the prostate is free of disease much more than Negative imaging. Also, doing transrectal bxs through radiated rectum is asking for trouble.

 

[DoctwoB]

Im not sure I see how the prostate biopsy will help you. Why would you be more or less inclined to do a PLND if you got a positive bx in the prostate? If the nodes are close to bowel and can’t be adequately addressed by RT the patient may still benefit from surgery. Also, I would imagine the false negative rate of random biopsies in this setting is pretty high. Not sure I would personally feel like negative bx of the prostate is all that helpful at convincing me the prostate is free of disease much more than Negative imaging. Also, doing transrectal bxs through radiated rectum is asking for trouble.

Was thinking Im not totally convinced by a cold axumin, especially given the brachy monotherapy for what was almost certainly unsampled high grade disease. You’re right though in that the NPV Of that biopsy may be low, though if positive it would effect management by adding radiation to gland.

 

[ramsesthenice]

Was thinking Im not totally convinced by a cold axumin, especially given the brachy monotherapy for what was almost certainly unsampled high grade disease. You’re right though in that the NPV Of that biopsy may be low, though if positive it would effect management by adding radiation to gland.

Re-RT after brachy is controversial at best. The best data is for focal HDR boost to the gross disease. If it is asymptomatic and there is no identifiable GTV on MRI or PET it’s hard to see a role for RT to the prostate gland at this time. I hear what you are coming from, I’m just not sure I really see it being fruitful at this time for technical reasons.

As an aside, the problem with brach and high risk disease is not the Brachy can’t treat high risk disease in the gland. If anything, high grade disease is probably more sensitive to RT. The problem is the same as it is for surgery: an increased risk of extraprostatic disease that is under treated. Not sure how that would affect what you bx.

This dudes tumor makes PSA. I really think you should treat the nodal disease as best you see fit and then track the PSA and worry about the gland down the road if/when it declares itself.

 

[evilbooyaa]

No up front MRI, just got a standard 12 core biopsy. Given his age/health definitely favoring being aggressive with LND + adjuvant XRT +/- ADT, but will see what my local radoncs think of tumor board (maybe do a prostate biopsy before hand to ensure no residual disease, because if so would lean towards just XRT up front).

OK, that makes more sense then (in regards to no pre-brachy MRI).

For cLN+ disease I would add 6mo - 2years of ADT even if doing surgery + adjuvant RT.

In absence of Auxumin positivity I don't see the utility of a prostate biopsy. Patient's cancer lights up on Axumin - if LNs are positive and prostate is negative, would treat LNs in salvage setting aggressively and monitor.