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Welcome to the Genitourinary (GU) Cancer Sessions with the Video Journal of Oncology (VJOncology).

Watch our expert roundtable discussions to learn about the latest advances in GU cancer research and what the data means for clinical practice.

In this exclusive VJSession, join GU cancer experts Sophia Kamran (Massachusetts General Hospital and Harvard Medical School, Boston, MA), Himanshu Nagar (Weill Cornell Medicine and New York Presbyterian, New York City, NY), and Neha Vapiwala (Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA) as they discuss some of the highlights in radiotherapy for GU cancers at the ASCO GU Cancers Symposium 2023.

In prostate cancer, key radiation oncology trials included FORMULA-509 (NCT03141671), RADICALS-HD (NCT00541047), CHHiP, and PACE-A. In bladder cancer, hot topics of discussion included the use of adaptive radiotherapy and a debate on when to use bladder-only or whole-pelvis radiotherapy. Finally, in testicular cancer, a key discussion compared the use of radiotherapy vs surgery vs chemotherapy for the treatment of stage 2a seminoma.

Prostate Cancer: FORMULA-509, RADICALS-HD, CHHiP, and PACE-A

 

 

 

 

“The past five, 10 years, I don’t want to say prostate cancer in the localized setting was boring before, but it’s gotten real exciting in a very short period of time”

Himanshu Nagar

Bladder Cancer: adaptive radiotherapy and bladder-only vs whole-pelvis radiotherapy

 

 

 

“I really think that this is a perfect population to really consider adapting the radiotherapy and the radiation based plan”

Sophia Kamran

 

Testicular Cancer: radiotherapy vs surgery vs chemotherapy

 

 

 

 

“There’s always something that you think, oh yeah, maybe we’re not going to explore that. But it has its way of perhaps coming back around”

Neha Vapiwala

Read Full Transcript

Sophia Kamran:

Hello everyone. We are here today at GU ASCO 2023. We’re very excited. My name is Sophia Kamran, I’m a radiation oncologist at Mass General Hospital, and I’m here with colleagues.

Neha Vapiwala:

Hi, I’m Neha Vapiwala. I’m a radiation oncologist at University of Pennsylvania.

Himanshu Nagar:

And I’m Himanshu Nagar, a GU radiation oncologist, from Weill Cornell Medicine, New York Presbyterian Hospital in New York.

Sophia Kamran:

All right. Great. So, Neha, what have you been very excited about in the world of GU radiation oncology here this year?

Neha Vapiwala:

Yes. Well, there is a lot to talk about today, but I guess I’ll start out with FORMULA-509, the multi-center randomized trial that actually is trying to evaluate the role of systemic therapy intensification in high-risk patients with post-prostatectomy biochemical recurrence. Particularly of interest to me given the ongoing ECOG-ACRIN 8191 indicate study that’s trying to look at a similar question of systemic therapy intensification.

So Dr. Nguyen presented yesterday and what was really interesting is although the primary analysis, which was looking at both metastasis-free survival as well as progression-free survival, the cutoffs were not met for those hazard ratios. There was some suggestion of benefit in patients, particularly with postoperative PSAs over 0.5. That was part of a pre-specified analysis and it was a subgroup that they looked at and there does appear to be some signal there. Although, interestingly, for the other subgroups in particular node-positive versus negative, there was not that benefit seen so far.

So it’s curious why that could be in terms of systemic therapy intensification with, in particular in this study, abiraterone, prednisone and apalutamide for a six-month duration. The hypothesis here is that our highest risk patients, the ones with the highest sort of pretest probability of failure after standard of care post-prostatectomy radiation and six months of androgen deprivation, that that should be the group that benefits. So I’ll be curious to see if over time, in addition to the patients with PSA over 0.5, will we also see progression-free survival and metastasis-free survival benefit in those node positive patients. That is at least I think in my practice, at least the patients where I am most interested in systemic therapy intensification. So interesting data.

Sophia Kamran:

Yeah, that makes sense. And what are your thoughts in light of RADICALS-HD in that study, given that that also was looking at the same type of group of patients, but it was looking at different types of systemic intensification more duration? So what are your thoughts on that?

Neha Vapiwala:

Yeah, and I think that’s exactly it is the form of intensification, right? Does it take on a long duration form? Does it take on a hit them hard upfront for a shorter period of time form? And I think this is where we’re still, I think, very much in this clinical quandary of what does your institution, what did perhaps you as a provider have more comfort with, particularly for toxicity management. We cannot forget that the toxicities of everything we do go on beyond the period of time that the therapies are delivered. And so your comfort level.

Then, of course, the patient side of things, the shared decision making piece cannot be understated. I think we each can probably tell stories of patients who are highly motivated, say “Hit me with everything you got,” regardless of what the data may or may not support in that setting. Then you have those that are really looking to minimize any exposure to therapies that compromise quality of life. So we’ll see with time how this evolves.

Sophia Kamran:

Yeah. No, I completely agree. I think that patient perspective piece, it’d be very interesting to kind of take a look at that and I think it really does require a multidisciplinary discussion and then sitting down with the patient and getting their perspective, getting their thoughts. So absolutely. Okay, great. Himanshu, what are you excited about? Anything that was presented that you’d want to talk about or highlight?

Himanshu Nagar:

Yeah. So yesterday was very interesting in terms of the localized prostate cancer setting along with the salvage prostate after prostatectomy setting. So two trials were presented yesterday that definitely perked up the ears and eyes of multiple audience members and social media.

The first one I’d like to sort of touch upon, which is more of a confirming analysis of the CHHiP trial, which they’ve already presented their five-year data and yesterday they presented their 10-year data and it was basically a randomized trial, mainly intermediate risk patients with prostate cancer, a majority of them received androgen deprivation therapy so what we would consider standard of care therapy for many of these patients right now. It was looking at three different fractionation arms, one more conventional in the 37 range, you had the 20 fraction arm and the 19 fraction arm. Surprisingly, the 19 fraction arm could not be called not-not inferior here to the 37 fraction arm, but it was very confirming to see the biochemical control from the 20 fraction arm. The toxicity remained low in the 20 fraction arm. So I don’t think it’s necessarily practice-changing, but definitely practice-confirming for those that have already adopted moderate hyper fractionation in 20 fractions.

That’s our practice for those that are patients undergoing moderate hyper fractionation, we tend to go with the UK standard of moderate hyper fractionation. So that was very reassuring because as radiation oncologists, we know that we love early data, we love early toxicity reports, but we know radiation and other therapies can have long-term side effects. So seeing this 10-year data is very comforting to all of us saying that we’re very comfortable with our recurrence rate and the low toxicity profile of basically cutting the fractionation scheme in half for these patients. It’s interesting because we always wonder why is that one fraction making sense?

Sophia Kamran:

Right. I was just going to ask, so what are your thoughts about that three ray? Yeah, what’s going on there?

Himanshu Nagar:

Is three the alpha beta ratio, and this confirms it that you need that extra fraction, but honestly it’s one of the conundrums I don’t think anyone has a good gestalt on as to why that extra fraction matters to call it not-not inferior to 37 fractions.

Neha Vapiwala:

I also sometimes wonder, you sometimes do get into scenarios. I think COVID pandemic certainly highlighted it where you might have an unexpected break and I don’t know that we have a good sense when as we are hyper fractionating can a patient who for whatever reason needs to miss a week because they’re COVID positive and they can’t come in. I’m always curious about what’s the impact of that. I don’t think we know.

Sophia Kamran:

Right.

Himanshu Nagar:

No, exactly. I mean we known and had a neck cancer and cerebral cancer, all those matter. And then prostate cancer, you’re saying, I don’t know, maybe you do actually need to come back to finish that last part.

Sophia Kamran:

Yeah, exactly. We need to insist on that.

Himanshu Nagar:

Randomized data like-

Sophia Kamran:

That one fraction.

Himanshu Nagar:

Not in theory.

Sophia Kamran:

Yeah, exactly. Just that extra three gray.

Himanshu Nagar:

Yeah, exactly. Got to get the dosing. And the other trial that definitely was understatement to say thought-provoking for all of us is the PACE A trial. So PACE is a brilliant trial design from PACE A, PACE B, PACE C, that some of it’s been presented in other meetings, but this one was focused on PACE A, which was the trial that we all wanted to happen. We’re glad that it happened. Randomizing patients with favorable intermediate risk, prostate cancer, and low risk to very minor low risk in this patient population to either radical prostatectomy with modern surgical techniques to compare to SBRT with modern radiation techniques. And I would say this is the primary toxicity analysis, which was the primary endpoint comparing urinary function, bowel function, and erectile function between both groups. And I would say it was definitely at least confirming of the ProtecT data.

We sort of saw the same sort of readouts in terms of the, I don’t want to say the absolute difference, but basically urinary and sexual quality of life was reported higher in the ProtecT data from those that underwent a radiation bowel quality of life slightly better with those that underwent surgery. I think what was surprising here is the urinary toxicity profile that we saw in terms of pad use at two years. Now, the devil’s always going to be in the details, so we’ll have to wait for the paper to come out and actually look at the granularity of the epic subdomains and what was actually happening. But I think a lot of us were a bit surprised to see that level of pad use two years out because I could say we all know our surgeons, we have great surgical practices, but this was randomized real world data. So I can definitely say we don’t see this level of pad use at two years after the process.

Sophia Kamran:

Yes. Yes.

Neha Vapiwala:

Thankfully

Sophia Kamran:

Yes. Thankfully. Yes, yes, yes. Thankfully.

Neha Vapiwala:

And I think one of the things that’s great that you bring up the ProtecT trial, because I know when those data did get published, one of the first thoughts from many of my urologic colleagues were like, well, those are not reflective of our outcomes and my patients don’t have that outcome. But the reality is, I think for many of us, depending on where we practice, it isn’t always realistic to say to patients, you’re going to have the best possible outcome. No long-term morbidity. And what these data are, I think very sobering in telling us is that actually, as you said, in real world data and real world outcomes. And we have to prepare patients for that worst case scenario because a number of factors can play into that, including surgical experience and expertise, so.

Himanshu Nagar:

And also what we focus on the pad use there. But from the radiation side, the bowel bother’s still there with advanced imaging and other sort of, let’s call them separation techniques. Yes. Can we minimize the bowel bother? And then again, devil’s going to be the details of the granularity is like what is that bowel bother in terms of the epic subdomain? How much of a bother was it in terms of diarrhea, etcetera. So really look forward to the paper coming out to really delve into the details.

And the third domain, which the delta on that was quite broad in terms of erectile function because ProtecT was a mixed group of patients. There was ADT in that this was no hormonal treatment, so this is just five fraction radiation. And we see there’s a decline in sexual and erectile function from both arms, but the delta from radiation to surgery is quite broad. So whatever the technique of radiation we’re using now in this trial and that we’re using our own practices is preserving sexual function at a greater level than what we once saw. So that’s promising for patients too, but again, we’ll have to wait for the final publication and not just trust what we’re seeing on social media at this point completely.

Neha Vapiwala:

And provocative question for you, what does this mean for brachytherapy to go?

Sophia Kamran:

I know, yes.

Himanshu Nagar:

I know. So SBRT, and that’s what we’re seeing. So we have PACE B data with toxicity. We’re going to wait for the outcomes of 20 fractions versus five fraction being the bulk of that trial. We have NRG, GOO5, that data is going to report out relatively soon too. So again, it boils down to speaking to the patient and what their comfort, what that shared decision making is, I would say LDR one fraction, HDR two fraction. But when you get down to five fraction SBRT, non-invasive approach, outpatient treatment come in from anywhere from 20 to 45 minutes a day. There are different technologies to minimize sort of the side effects of the urinary bowels subdomains now. So it’s going to be interesting. And internationally, there’s multiple five versus two radiation trials going on now. So if you get down to two fraction SBRT brachy is going to be, I love brachytherapy, but it’s going to be proposition value that’s going to be difficult.

Sophia Kamran:

I know it’s going to be tough. That is definitely an area.

Neha Vapiwala:

I often say to my patients who are in this scenario, the good news is you have a lot of options. The bad news is you have a lot of options.

Sophia Kamran:

You have options. Yes, exactly.

Neha Vapiwala:

The angst of it all. And all of us are angst-ridden as well because there aren’t necessarily easy distinctions. But you know what? It’s an incredible world to be living in that we have all of this cancer research and discovery and ability to be able to offer this.

Sophia Kamran:

To offer all these treatments to our patients.

Himanshu Nagar:

The past five, 10 years, I don’t want to say prostate cancer in the localized setting was boring before, but it’s gotten real exciting in a very short period of time.

Sophia Kamran:

A lot going on. Yes.

Himanshu Nagar:

So what excite-

Sophia Kamran:

Yeah. It’s not all about prostate cancer. Okay. All right. So yes, speaking about advanced technologies and radiation is just, the field has exploded. So I’m going to talk a little bit about bladder cancer. So there are two very interesting abstracts that were presented that I just want to highlight, that thought-provoking, and I think they’re pretty exciting. So adaptive, which Himanshu mentioned earlier, adaptive radiation therapy where we actually adapt the treatments every single day for patients. They actually studied this for bladder cancer patients and bladder cancer patients, this is a tough situation because there’s just a lot of bowel, normal anatomy in that area. So I really think that this is a perfect population to really consider adapting the radiotherapy and the radiation based plan. So essentially they presented looking at dose escalating and adapting the radiation, and they were comparing it, looking at whole bladder and then tumor boost and then adapting and escalating the treatment.

And essentially it was very well tolerated. That’s basically the bottom line. And I think that that was very, very exciting. I think that this has a lot of implications for our bladder patients moving forward, particularly if we’re going to be adding on novel therapies like immunotherapy. We’re always worried about bowel toxicity that kind of came out when you hypo fractionate or you try to accelerate the treatment, you’re a little bit worried about that bowel toxicity, but perhaps adaptive radiotherapy. That’s kind of where we need to go for these types of patients. The other thing that was pretty exciting and very thought-provoking is there’s a big question when treating the bladder with radiation, do you treat the whole pelvis or do you just treat the bladder only? And there’s really two minds about it. They say across the pond, but in the UK it’s really bladder only.

And then here in the US a lot of the standard is doing whole pelvis. And really it’s never been compared head to head. So the data essentially showed that there might be a benefit to treating whole pelvis compared to bladder only. Obviously it’s thought-provoking. It hasn’t been studied in a trial setting. So I think that it’s just something to definitely consider because I think a lot of people do have the standard as being whole pelvis. And of course there’s a lot of people that treat bladder only. I don’t know. What do you guys do actually?

Himanshu Nagar:

Yeah, I treat bladder only. For bladder preservation. I’m a big fan of the UK in adopting-

Sophia Kamran:

Yeah, yeah, yeah. Yes, I can tell. Yeah. Yeah.

Himanshu Nagar:

But a long way with the RAIDER trial that you were talking about, it was great to see the dose escalation, the adaptive. And we’re worried about the urinary toxicity too. And we didn’t see significant increase in the grade three urinary toxicity because a lot of these patients are coming in with baseline urinary attack function issues. So it’s very nice to see an adaptive platform, a dose escalation platform. And you know, never want to do cross trial comparisons or historical control, but the bladder intact rate and event-free survival is getting higher from each subsequent trials.

So where even if you look at the meta-analysis that was published in the Lancet not too long ago between BCAN and BC 2001, this is sort of moving the needle up in terms of, so we’re getting better at what we’re doing working in a multidisciplinary approach with our medical oncology colleagues and urologists in terms of systemic therapy and offering bladder preservation. But to echo Sophia’s point, the adaptive technology, we’re already seeing evidence of it in prostate cancer toxicity. We’re now seeing it in bladder cancer from toxicity. So it sounds simple, but if we radiate what we want to radiate and avoid radiating what we don’t want to radiate.

Neha Vapiwala:

Which has always been the deal.

Sophia Kamran:

Yes.

Himanshu Nagar:

But I think we have the tools in the armamentarium to really deliver therapeutic radiation and move that profile toxicity versus control much further now.

Neha Vapiwala:

And I’d just like to point out the whole pelvis saga clearly transcends many of our disease sites. But I do think, and to just underline everything that you said, Himanshu, I think the patient selection piece is also so key. And that’s where these multidisciplinary tumor boards, because when we pride ourselves on improving toxicity and essentially decreasing it with all these techniques, a lot of it does really also have to do with the patient and their baseline and all those other factors as well. So I think that’s something we’ve also improved on over time. And how about testicular?

Sophia Kamran:

Okay. Oh, yeah. Lastly, I just also want to say we don’t forget about testicular. Testicular hasn’t really had its heyday in a while actually, but I think it’s really coming back. And so I just want to highlight that tomorrow we’re actually going to see a very exciting debate during the testicular session for stage 2a seminoma specifically. So essentially historically for stage 2a seminoma, it’d be treatment with either chemotherapy or radiation therapy specifically. It’d be more like BEP chemotherapy. Radiation is delivered in a dog-leg field and then doing a boost to the involved node. And recently there’s been some pretty exciting trials kind of opening up options for these patients. In particular, surgery is kind of back on board with RPLNDs. And so there’s been a couple Phase II trials that have been presented and published that kind of show really promising and exciting data for these patients.

And then in particular, there’s also a unique trial that was published SAKK01/10 that was actually looking at combining low dose chemotherapy and involved nodal radiotherapy, really kind of taking both the chemo and radiation piece and deescalating both of those therapies and combining them for stage 2a patients. And the results were very, very promising. Again, it was a Phase II trial, but it was very exciting. So we’re really going to have the three disciplines duke it out tomorrow. So we’ll see who wins. But-

Neha Vapiwala:

Very exciting.

Sophia Kamran:

But we’re all winners actually. We’re all winners.

Neha Vapiwala:

We’re all winners as long as the patient-

Sophia Kamran:

The patient wins. Yes. It’s all about patient care.

Himanshu Nagar:

As long as the options are on the table.

Sophia Kamran:

Yes, exactly.

Neha Vapiwala:

I got to say, there’s so much in oncology, right? It’s like the bell-bottoms. They make their comeback. There’s always something that you think, oh yeah, maybe we’re not going to explore that. But it has its way of perhaps coming back around. And then it’s some different form and seeing the benefit of it, we always want to keep an open mind.

Sophia Kamran:

Yeah.

Neha Vapiwala:

That’s great.

Himanshu Nagar:

Yeah, so far, I think very exciting. ASCO GU 2023.

Sophia Kamran:

Yeah, it’s been a very exciting meeting.

Himanshu Nagar:

It’s one of the true multidisciplinary meanings out there where everyone gets to present their data and everyone gets to learn from each other because we get to bring our multidisciplinary tumor board to the world.

Sophia Kamran:

To the world. Yes, exactly. Exactly.

Neha Vapiwala:

So stay tuned for tomorrow.

Sophia Kamran:

Yes.

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Disclosures

Recording date: 17-Feb-2023