Radiation Therapy for High-Risk Prostate Cancer: Which Modality is Best?

[Dr. Aditya Bagrodia]
…Then of course there's the actual type of radiation. Even at the beginning of my career, it was pretty easy to give a little synopsis of what's out there. Now, it's conventionally fractionated IMRT, hypofractionated, ultra-hypofractionated, combination, protons. Maybe this would be a good time for me to request that you share your spiel, if you will, for a high-risk prostate cancer patient, including efficacy and complications.

[Dr. Daniel Spratt]
Yes. I'll give you my take, and I know that there are definitely radiation oncologists that would feel differently, but what I tell guys for high-risk disease is, first of all, I do not feel there's much of a role of conventional fractionation. I just looked at some practice patterns, and still, probably, I think it's 50% of the US uses conventional fractionation for high-risk. They say because you're treating lymph nodes, maybe we need to do that. For me, I think we've got great data. There's no role for that. To me, giving eight to 10 weeks of radiation therapy should be a rare scenario.


I think the addition of brachytherapy, I tend to-- I've written a lot about this, and had some nice debates with American Brachy Society members, I think that the data to add brachytherapy boost shows a small PSA benefit, and when I mean small, call it 10%, maybe as time goes on, it obviously expands, for a 20-plus percent increase in severe toxicity, including those couple of deaths on the Ascende-RT trial. Quality of life, even for high-risk men, in modern high-risk trials, I often say if you look at-- there's a trial called FLAME, which was just external beam with a external beam boost, or this trial called POP-RT from India, which is just external beam, modern high risk. It's like 1% of guys are dying of prostate cancer in 5 to 8 years.


Only 5 to 10% even have BCR in five years. This is very different than 30 years ago, given the staging and stage migration, grade migration. Anything that severely increases toxicity, or has the potential to, to me tips the favorability in the opposite direction, because I think we've learned this from the surgery plus or minus adjuvant radiation. The whole concept was, "You can give salvage. There's no difference here. You can give external beam, and for that maybe 10% of guys, you may have cured by giving brachy, you can do it as salvage if you need." It doesn't preclude you from that. I think that given there's no metastasis-free survival benefit of doing these ultra-high doses, I do not personally recommend it. I probably do more than the average regarding ultrahypofrac in high-risk and we've run a number of trials.

[Dr. Aditya Bagrodia]
Dan, let me ask you real quick. Just for brachy, are we talking about low-dose seed implants or high-dose catheters?

[Dr. Daniel Spratt]
Yes. There's no level-one data for HDR. I think HDR is probably-- I think objectively, although there lacks good evidence, has less toxicity than LDR. I think many people have pivoted over to HDR.

The problem is that there's no level one data for HDR compared to just dose-escalated external beam. I think what the field has done is they hear the word brachy and they just think it's all the same. There's been some big teaching points in that they said, "Oh, well, let's just do HDR single fraction." LDR is just one insertion. It was in low-risk disease, 40% of these guys recurred. The danger, and I call this out a lot in radiation oncology is, just because you call it brachy, or just because you call it radiation there's no dose escalation trials. We don't know what the optimal dose is. It's retrospective. Do I think it is safer? Yes. Do I think it necessarily improves outcomes? I have no clue.

[Dr. Aditya Bagrodia]
No, I appreciate that. Maybe if we go with most intensive, which would be combined brachy plus external, sounds like unless you have a hyper-motivated patient that wants to do everything in God's green earth to be as aggressive as possible, recognizing that comes along with some additional toxicity, that's not going to be your standard recommendation.

[Dr. Daniel Spratt]
No, I'd be doing, as I referenced that FLAME trial where you do an external beam boost. It showed a near identical PSA, or biochemical control benefit, as adding an LDR boost with functionally, 0% increase in toxicity, and doesn't add the cost of adding an LDR implant. I know this is not loved by the brachy community, but I think doesn't devalue its role. It's just it may be better as a salvage option, or when you can be as monotherapy in earlier-stage disease.

[Dr. Aditya Bagrodia]
Combination, maybe not top choice. I'm a little surprised with the conventionally fractionated. In my mind, that's like you can get this at a quaternary cancer center or you can get it with Joe Schmo and the sticks and good old fashioned eight weeks, five days per week, conventionally fractionated radiation therapy. Pros are friendly fire at a high dose to adjacent organs and associated toxicities are low. You can get the lymph nodes. We'll maybe talk about that explicitly. That's a big pro, I guess, accessibility where you don't have to work on a really refined, robust team to get the planning and the imaging. Absolutely perfect for things like ultra-hypofractionated, maybe just a little bit more on--

[Dr. Daniel Spratt]
Yes. I completely agree with your assessment when you compare to ultra-hypofractionated. When you talk about four or six weeks of what's called moderate hypofract, so there's trials, one called PROFIT and another called CHIP, but in PROFIT, there's actually less late toxicity using 20 fractions of radiation. You do not need ultra-specialized equipment to give 20 to 28 fractions of radiation therapy for prostate cancer instead of 40 to 45 treatments. Is it wrong to do 40 to 45? No. Is it as convenient for the patient or we'll call it cost effective? No. About once a year I have a guy who literally says, "That's what I want," and to me, I view them as they're non-inferior when each done correctly but I do think in similar to other cancer types, why do something that adds patient burden if there's no benefit?

[Dr. Aditya Bagrodia]
As you'd mentioned with the FLAME trial, ostensibly with the boost, there's something about that higher dose per fraction in terms of cell kill that's a value versus just getting the ultimate dose in over a longer time.

[Dr. Aditya Bagrodia]
I guess, are there symptom or size-specific factors that precludes people from receiving less fractions?

[Dr. Daniel Spratt]
Generally, we're talking if these glands are, we'll call it around 100cc or less, is that I think some of the data that some of it came from Dr. Pollock and this moderate hypofrac trial that I think stuck in people's minds. It's really old data that doesn't seem to be reproduced in other trials that they say, "Oh, if you've got obstructive symptoms or large glands, don't do hypofractionation." It really doesn't seem to bear out. That's really not a reason. If a guy has obstructive symptoms, I do SBRT or moderate hypofrac. They're going to equally have side effects. It's not like if you do conventional, they're going to have no worse side effects from it. Many of my guys I feel that prefer a shorter acute phase, then there's eight, nine weeks of just chronically having this irritation, and they're like, "Let me put them on some ibuprofen if you need, or Flomax, give them a couple of weeks of SBRT and get through it," and you're done.

[Dr. Aditya Bagrodia]
Yes. I really liked the analogy that Neil Desai gave, which is, do you want me to rip off the bandaid or do you want me to pull it off slowly? Maybe that's a memorial thing from Zelefsky and company, but I think that's what it boils down to. It's like, "Do you want this in a shorter, condensed format where there may be a little bit more urinary and rectal toxicity or do you want it a little bit slower where there's a lot more involvement interfacing with the health care system and maybe the toxicities are a little bit more acceptable?"

[Dr. Daniel Spratt]
I'll say that I don't think there's actually lower toxicity. I think that the late long-term toxicity is really the same in the studies. They're superimposable. The early phase, the acute first 90 days, you're spot on. That goes back to that analogy of ripping it off versus slowly peeling it off. I think if we're talking about one year, two years, five years, et cetera, it's the same.

[Dr. Aditya Bagrodia]
Just to make sure that I'm clear, so ultra-hypofrac, that's five fractions administered basically every other day for a couple of weeks?

[Dr. Daniel Spratt]
Yes, usually. Like always, there's exceptions. People do four, some people do six or seven but generally, it's five. Generally every other day. Some people do it once a week, some do it five days in a row, but generally every other day.

[Dr. Aditya Bagrodia]
Maybe now I would just request you to walk us a little bit through the logistics, some of the considerations, fiducials, SpaceOARs, when are you using those or using them routinely. The patient's decided on radiation for the high-risk prostate cancer, walk us through a little bit about, "Hey, Mr. Smith, this is what the next four to six weeks looks like."

[Dr. Daniel Spratt]
What we would do is we would get-- Whether it's an oral or if it's an injection for ADT, get that started. Usually, if it's going to be an injection, we try to link that up with one of his early visits just so it's not multiple visits. First step for us is for most guys it,'s got to be pretty bad disease with true posterior extracapsular extension. Not posterior lateral like in the neurovascular bundle, but true posterior to not do a rectal spacer. I partner with our urology group, it's the way we've streamlined it here. Yoni Shoag and this guy, Randy Vince, but Yoni will do 5 to 10 spacers on Tuesdays and just boom, boom, boom back to back, just knock them all out, and he'll put fiducials in at the same time. Spacer goes in--

[Dr. Aditya Bagrodia]
Let me ask you a quick question, Dan.

[Dr. Daniel Spratt]
Go for it.
This is something that actually came up in our tumor board yesterday. There was a patient who had 160cc prostate, clearly extracapsular extension. It was posterolateral, extending a bit towards the midline and we were having a whole discussion, and SpaceOARs came up and this idea of ECE posteriorly being a contraindication was mentioned. I was thinking surgically when you go wide, you can either get right onto your longitudinal rectal wall fibers or you can get onto the perirectal fat or you can get into a interfascial nerve spring plane. When you inject your SpaceOAR, I'd also imagine, of course, you don't want to get into the rectal wall and have to sort through all of that, but if you stay wide, could that potentially allow you to deliver a more effective dose or have a bit more of a margin to spare the interior wall and still address that disease?

[Dr. Daniel Spratt]
Oh, 100%. For me, like I said, it's probably almost all of my guys with high risk. There are people who say if it's high-risk you can't do a spacer. If there's ECE anywhere, you can't do a spacer. The plane as you're saying behind [unintelligible 00:45:17] if you're in the right plane, you shouldn't be dissecting through tumor and separating it at all. That's where I say it's got to be those cases that you're like, "Is there a rectal invasion? I'm not sure on the MRI." Those are the cases I don't do it, but the vast majority I think it's safe to do. Again it's partnering-- there's Rad Oncs who do a great job placing them. I have found both at my last center and here having a go-to one or two urologists that I can show the SIM images and they're just logistically able to knock them out, they get super proficient. The Rad Oncs, some, who are fantastic but they'll squeeze it in between consults. It's not necessarily like they're ultra in the zone, but for high-risk, I don't have concern about it.

[Dr. Aditya Bagrodia]
I personally don't think, fast forward 10 years, we're going to see a bunch of recurrences posterior to where the spacer, which is now gone, used to be. SpaceOAR or rectal SpaceOAR, I guess it's proprietary that fiducials, that that happens. SIM, CTs, MRIs, molds?

[Dr. Daniel Spratt]
Yes. I would say if it's a guy coming locally, about a week later we do a SIM. If a lot of my patients come from another city or state, I do it the next day just so they spend one night in a hotel. It's a CT. If they've already had an MRI, I actually don't get another MRI. We just register the initial MRI, even though the spacer's there now just to save them the cost of another MRI. If they've got hip prosthesis or something, then I'll get another MRI just for target delineation. Then planning, obviously, we use a variety of auto contour tools and we're always trying to speed up that, but I would say about a week later they're ready to rock and roll, start treatment. They got it mobilized at the time of SIM and they're ready to start.


[Dr. Aditya Bagrodia]
Then we're getting onto treatment, usually what? An hour, hour, and a half for the A to Z experience? Is that about accurate?

[Dr. Daniel Spratt]
Here, my spiel and it's pretty spot on if the guys-- usually we have them drink water before they come in. It's usually 45 minutes door to door. The beam is on for six minutes but they've got to get on the table, they do some imaging, adjust them, treat them. These guys will have a full bladder, they got to go pee afterwards. It's about 45 minutes and that was pretty consistent in my last center. There I used to say 45 minutes car door to car door because in Ann Arbor, we'll say parking was easier. Once you already start to be in a city, even though Cleveland's not a massive city, parking adds some time. I imagine San Diego if you throw in some of that.

[Dr. Aditya Bagrodia]
That's the single biggest complaint from our patients, are parking in valet and things along those lines. Generally, let's maybe say an hour A to Z.