What’s New in Prostate Cancer Radiation Oncology

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances, a Cleveland Clinic podcast for medical professionals, exploring the latest innovative research and clinical advances in the field of oncology. Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale Shepherd, a Medical Oncologist and Co-Director of the Sarcoma Program at Cleveland Clinic. Today I'm happy to be joined by Dr. Shalini Moningi, a Radiation Oncologist specializing in GU cancers here at Cleveland Clinic. She's here today to discuss the latest advances in radiation therapy for patients with prostate cancer. So welcome.

Shalini Moningi, MD: Thank you so much for having me. Excited to be here. Yeah, so I'm a radiation oncologist. I specialize in radiation treatment for prostate and bladder cancer, and I'm the Co-Director of the Genitourinary Program here at Taussig.

Dale Shepard, MD, PhD: Excellent. So we are going to talk about advances in radiation therapy for prostate cancer. So certainly radiation has been a big component of prostate cancer in the past. Tell us a little bit about what the problems were with where we were and how we're working to make improvements.

Shalini Moningi, MD: Yeah, no, that's a great question. We've come a long way with radiation treatment and prostate cancer. In the past, a few decades ago, we would do more conventional fractionation treatments, which were longer courses of treatment up to 40 treatments, which is about close to nine weeks. We've now shortened our radiation treatment courses to more of a hyperfractionated approach, which is as little as four weeks. And now beyond hypofractionation, we also do something called stereotactic body radiation treatment, which is only five days of radiation treatment. So we're able to safely deliver a high dose of radiation to the entire prostate gland over a course of only five treatments. We do that with improved imaging guidance, and we also do that with improved technologies such as AI and contouring technologies.

Dale Shepard, MD, PhD: So when you have people who traditionally may have known someone who got really long courses of radiation or even providers that are referring, how has the shorter courses of radiation been sort of perceived? I guess they like not being involved with radiation for as long. Is there a concern about shorter courses with patients?

Shalini Moningi, MD: Yeah, that's a great question. So there's been a lot of work in trying to figure out who the right patient is for SBRT. I think patient selection is really important. We've had a couple of prospective trials looking at SBRT and toxicity. And we've found that patients that have more of a prostate gland size of less than 70 CCs do better with prostate SBRT. Also, patients that have decent urinary symptoms upfront do better with prostate SBRT. So not everyone is a great SBRT candidate. Now if they are, I think it's really well tolerated and patients love it. They love coming in just for five days. We also have currently a national cooperative group trial looking at five treatments versus a higher number of treatments to look at toxicity long term. So it's an ongoing process, but currently we have a pretty good idea of patients who would do really well with prostate SBRT and we're starting to use it more and more.

Um, what's really exciting in our field in addition to that is we are also using something called adaptive radiation. And that's sort of the new exciting thing in radiation where currently when you come in for radiation treatment, we create a plan for you after your mapping scan. And then once you start treatment, you get that same plan every day. Adaptive radiation treatment allows us to actually make a new plan for you every day of treatment. And so that's something that we're really excited to start using, especially when we give SBRT, which is high dose per treatment.

Dale Shepard, MD, PhD: And that actually is going to be starting here at the beginning of the year that we're going to be doing more of that. Is that right?

Shalini Moningi, MD: That's right. So we're actually going to be getting a machine called the Ethos machine. And what that machine does is it actually delivers radiation just like our regular linear accelerators. We do cone beam CTs, which are CT scans every day. But what's really cool about this machine is it uses high diagnostic level CT scans and combines that with AI technology to help us make a radiation treatment plan every day based on the patient's anatomy that day. It helps save time and then we'll have physics and a physician review those plans before that plan is delivered to that patient.

Dale Shepard, MD, PhD: Which is pretty impressive because usually in the old days, right, the physics side and creating the plan took a fairly long period of time, right?

Shalini Moningi, MD: Completely.

Dale Shepard, MD, PhD: And so that's fantastic.

Shalini Moningi, MD: Yeah.

Dale Shepard, MD, PhD: And then I guess just not to get in the weeds, but if you have a tumor that's changing sized, you're trying to avoid normal structures as much as you can, but are you still trying to sort of essentially radiate the same field that you started with or do you shrink the field as the tumor shrinks?

Shalini Moningi, MD: Yeah, that's a great question. So with prostate cancer, it's interesting. Studies have actually shown that with SBRT, the prostate gland can actually swell and go up to about 10% more than its original size. And we don't actually account for this with our regular radiation plans if you're getting the same plan every day. So with something like Ethos, we're able to expand that volume to account for that. Now, in addition to just the prostate volume, we're able to do two other cool things. And we can do this also without ethos, but something that we're starting to do more of is we put a rectal spacer in between the prostate and rectum to help protect the rectum further from high doses of radiation. And we're also able to give boost doses or higher doses to areas of cancer seen on the MRI within the prostate. So the entire prostate doesn't necessarily get a homogenous dose.

You'll see areas where we're boosting, where we've had primary cancers seen on the MRI. So we're able to personalize a treatment truly, not only for every patient, but for every day of treatment.

Dale Shepard, MD, PhD: As we've changed radiation techniques, when I was first out of fellowship, I treated a fair amount of prostate. And one of the big things, sometimes I felt like I was the tie breaker between surgery and radiation because they've gotten two opinions and they're like, what do you think? Have there been any differences in terms of toxicity profile as we change the radiation? Is there anything that's going to point to an advantage of one over the other in some situations?

Shalini Moningi, MD: Yeah, that's a great question. And my surgery colleagues can speak better about surgery, but I think there have been lots of advances with surgery techniques as well. With radiation, I feel like over the past decade or so, the toxicity profiles have actually been better for a couple of reasons. One, we have things like this gel or adaptive radiation, but second, we've actually been able to have tighter margins on our volumes because we have better imaging. So every day you're getting a CT scan and we're able to see what we're treating. And that allows us to have a smaller volume and a smaller expansion outside of the prostate, which helps leads to decrease toxicity. So all of those things really help. And in addition, recently, we've also been doing something called a urethral sparing approach. So the radiation dose to the urethra really leads to a lot of toxicity, especially urinary toxicity in patients.

And so now we're able to deliver SBRT with the urethral sparing approach to help protect that region and really help patients with further decreasing their urinary toxicity. So there's definitely a lot of ways we're able to decrease urinary toxicity. At the end of the day, for patients that have lower risk or intermediate risk cancer, they truly do have a choice between surgery and radiation. And a lot of that really depends on the types of symptoms they would rather experience, whether that's incontinence versus really urinary frequency, which is the latter is what we mainly see with radiation.

Dale Shepard, MD, PhD: So I guess the other thing, just to sort of touch base, proton therapy.

Shalini Moningi, MD: Yeah, that's a great question.

Dale Shepard, MD, PhD: That's always a question. As we do SBRT and we change fields and get less toxicity to nearby structures, where does that fall in?

Shalini Moningi, MD: That's a great question. There's been a lot of chatter about proton therapy and prostate cancer. Now, I personally trained in a place that has proton therapy and I've had a lot of experience in that. And I will say proton therapy is great in specific scenarios. It's great in scenarios where there are organs at risk right beside the structure. We think about CNS a lot. We think about craniospinal radiation a lot and also radiation for children. Now, there was a recent study coming out of MGH with some of my colleagues that I used to work with looking at proton radiation treatment for prostate cancer. And they actually found that there was really no difference in survival rates, recurrence rates, and not a huge amount of difference in toxicity as well. And I think one of the reasons why is because when we use protons for prostate radiation treatment, we use lateral beams that come from each side of the body.

And then we have this gel that really separates the rectum from the prostate. So there's really not a lot of benefit in terms of organs at risk and toxicity from protons. So when patients come to ask me about prostate treatment and protons, I'm kind of neutral about it. And honestly, some of my colleagues who've treated with protons are also a bit neutral about it. I think you can go that way. There could potentially be a slight decrease in toxicity, but currently data doesn't really point to it.

Dale Shepard, MD, PhD: It seems like you've come up with good ways to mitigate the toxicities with photons. It takes away the advantage of proton.

Shalini Moningi, MD: Yep, exactly. Exactly.

Dale Shepard, MD, PhD: Interesting. Let's change gears really quickly. Biomarkers. How have biomarkers become important in treating prostate cancer?

Shalini Moningi, MD: Yeah, that's a great question. There's been a lot of discussion, a lot of work in the biomarker space in prostate cancer. We've done a very good job in offering different treatment options in every stage of disease for prostate cancer, but really now as a group, we want to personalize treatment and specifically we wanted to use biomarkers to help with saving patients from toxicity from hormone therapy. As you know, hormone therapy decreases testosterone in your body and can cause a lot of havoc. And so there's been a lot of research in biomarkers. A lot of that research has been retrospective or secondary analyses of large trials. However, this year at ASTRO, there's been a new study that was a prospective study called the Balance Study, and they looked at PAM50, which is a biomarker that was actually used in the breast cancer literature. And they stratified patients who had PAM50/luminal B component of their prostate cancer.

And they basically stratified patients who had that mutation and expression versus patients who did not have that. And these were patients who've already had surgery for their prostate cancer and now have a recurrence and are being considered for radiation after surgery. And what they actually found was that the patients that did have this genomic signature benefited more from hormone therapy than patients who did not have this genomic signature. So you can imagine we're actually saving a lot of these patients from unnecessary hormone therapy if we find out that they don't have this genomic signature. So it was the first time that we were able to see this in a prospective way, which is really exciting. So now in clinic, we're actually able to get this genomic signature based off of their surgical pathology. So no additional blood test is needed. We just send the path slides over and we're able to decide whether this patient can get hormone therapy or not in addition to radiation treatment.

So it's really exciting to see some of this data. There's also current trials with the NRD and our cooperative groups looking at biomarkers and stratifying whether patients get a longer course of hormones or not in different disease stages for prostate cancer. So more to come in the upcoming years, but this was sort of the newest and most exciting work that has just come out of our field.

Dale Shepard, MD, PhD: You talked about patient selection in terms of SBRT approach versus longer courses. Is there any consideration of biomarkers in terms of that patient selection?

Shalini Moningi, MD: That's a great question. There is currently some ongoing work looking at biomarkers and selecting patients who might benefit from dose escalation of treatment. So higher doses or higher BEDs to the tumors. Currently, there's really not a lot of data yet, but I'm hoping to have some as a field in probably the next couple of years.

Dale Shepard, MD, PhD: I guess another area, I'm just throwing out all kinds of things that have come around in the past. What about the role of radiation in treating a primary tumor in the metastatic setting?

Shalini Moningi, MD: That's a great question.

Dale Shepard, MD, PhD: Yes.

Shalini Moningi, MD: That's perfect. We've talked a little bit about adaptive radiation treatment. We talked about biomarkers. What's really exciting in the GU field over the last one to two years is that there have been increased indications for radiation treatment in prostate cancer. Traditionally, radiation treatment was offered for intermediate risk, low risk, and high risk prostate cancer. In the last five to ten years, we've also been offering radiation treatment for something called oligometastatic prostate cancer where patients have less than five areas of metastatic disease, and that's been shown to improve overall survival. There is a recent trial within the last year actually now showing benefit for patients with metastatic prostate cancer that don't necessarily only have oligometastatic disease. So someone can come in with areas of disease over 10 spots in the body and they would actually still benefit from prostate radiation treatment.

And what they found was that prostate radiation treatment actually decreases the chances of genitourinary complications down the line. So it decreases the chance of this patient needing a catheter, needing further surgery, or needing a TURP down the line. And it also improves biochemical control of disease within the prostate. So now really radiation to the prostate is indicated in all stages of prostate cancer.

Dale Shepard, MD, PhD: So I guess when we think about radiation as a modality within the prostate area, and of course hormones are being used with radiation. Any other combinations with systemic therapies that are promising at this point?

Shalini Moningi, MD: Yeah. So we talked a lot about kind of biomarkers and radiation. Something that is a type of radiation that we share with our nuclear medicine colleagues is called radiopharmaceuticals. Something specific that I want to talk about is Pluvicto. Pluvicto is basically a radioactive ligand that is connected to something called a PSMA, which is an antigen that's seen on prostate cancer cells. So Pluvicto is given via an IV infusion, and it basically targets prostate cancer cells all over your body.

Traditionally, Pluvicto has been used in the metastatic setting for patients, specifically the castrate resistant setting, meaning these are patients that don't respond to hormone therapy, would get Pluvicto. Now, recent trials have actually shown the benefit of Pluvicto now in the hormone sensitive setting, meaning the patient who has newly diagnosed metastatic prostate cancer could actually be considered for Pluvicto. Additionally, there have been recent trials looking at Pluvicto in the oligometastatic setting, either replacing hormone therapy or delivering Pluvicto with a decreased duration of hormone therapy.

The goal of all of this is to really improve patient's quality of life. We have patients with prostate cancer who have metastatic disease that live a really long time, right? And we want them to live and be healthy and feel comfortable. And hormone therapy really takes a toll on someone's body. And so our goal eventually is to hopefully decrease the duration of hormone therapy even in these metastatic settings by potentially offering something like Pluvicto in addition to ADT. So it's really exciting. It's definitely a moving target in terms of treatment options in the metastatic setting. And I think every year we're going to have newer and newer indications, which is awesome for our patients.

Dale Shepard, MD, PhD: I guess we're getting newer and newer things. What's missing? What do you think is going to be the next thing that's going to make a big difference? What excites you out there that's being developed?

Shalini Moningi, MD: What I'm super excited about is a combination of biomarkers and the need for Pluvicto. So right now there has been a lot of push in looking at potential biomarkers for patients who might benefit from Pluvicto over hormone therapy. So I think that's going to be the next push. As we offer Pluvicto earlier and earlier in the treatment of prostate cancer, the question is going to be, who should we offer it to? Who are the right patients who are going to respond to it? And that's still up for debate.

So I think the increased use of biomarkers is going to be helpful, but I think it's going to be helpful in specific patient scenarios and trying to really pick out the patients who are going to benefit from increased Pluvicto or decreased hormone therapy or dose escalated radiation treatment. So I'm really excited about that. And there's actually a lot of work that we're doing in our GU group here as well on the subject and then also all around the country.

Dale Shepard, MD, PhD: Wow. Lots of changes.

Shalini Moningi, MD: Yeah.

Dale Shepard, MD, PhD: So certainly a lot of innovation. It's not just primary radiation for prostate cancer anymore.

Shalini Moningi, MD: Yeah.

Dale Shepard, MD, PhD: Appreciate all of your insights.

Shalini Moningi, MD: No, thank you so much for having me. Excited to be here. And I think it's an exciting time here at the Cleveland Clinic.

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