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Cheryl T. Lee, MD: Welcome to Medscape InDiscussion for season two of our bladder cancer series. I'm Cheryl Lee. Today we'll discuss stereotactic body radiation therapy (SBRT) and its role in treating oligometastatic bladder cancer or low-volume bladder cancer metastases. What are some of the key clinical outcomes when using SBRT in this setting? What current trials should we be watching? How does SBRT support quality of life from the patient's perspective? To further explore the combination therapy for advanced bladder cancer management, we've invited Dr Shekinah Elmore to our conversation today. Dr Elmore is an assistant professor and director of the Metastatic Disease Program in the Department of Radiation Oncology at the University of North Carolina Lineberger Comprehensive Cancer Center in Chapel Hill, North Carolina, where she's also a member of the Urologic Oncology Program. Welcome, Shekinah.
Shekinah Elmore, MD, MPH: It's so good to be here. Thank you.
Lee: I think our audience would enjoy understanding your background. It's no secret that you had an incredibly poignant TEDMED talk about your experiences as a cancer survivor of three malignancies. Can you tell us about your journey to radiation oncology and your motivation to discuss your personal story so publicly?
Elmore: Thanks for that. I think my journey to radiation oncology is a little bit different than your average doctor. I went into medical school thinking I would stay far away from cancer care because of my experience with illness, but I was drawn time after time to the patients who seemed a lot like me. I felt that I had insights, and I usually don't express them directly to patients because it's about them. But I have heard from so many people that sharing my story has been really meaningful for them, and I really did it hoping that it might resonate with others. And I think it has, and I'm so glad about that. I love this unique role of being a survivor and a provider.
Lee: That's outstanding. I know many people in our profession really look to individuals like yourself to help us think about the patient perspective while we're delivering therapy. So, thank you for sharing your story. Today, we're going to talk about SBRT. In the context of genitourinary malignancies, we're seeing a greater focus on treatment of not only primary disease and distant disease in the context of systemic therapies, but also thinking more about treating patients in the setting of oligometastatic disease, or just a small number of metastases, perhaps solitary in nature. This is certainly an area where there's a lot of investigation going on. I'm wondering if you could talk about the expanding role of SBRT in this context and particularly for bladder cancer.
Elmore: Absolutely. I think SBRT is so exciting and another maybe zingier name that's often used in Canada and maybe the rest of the world is stereotactic ablative body radiotherapy (SABR). We like it, and we are seeing it expand more because it's highly conformal, as we would say. It's really focused in, and it can be the right technique to treat less tissue, which we love. It's not always the right tool for its use, but it can be a good one. It can really benefit many patients, bladder cancer patients included. It may have better pain control outcomes for sites of bone disease. That's something that's under active investigation. There was just an abstract presented at the European Society for Radiotherapy and Oncology (ESTRO) that said there's better pain control with SBRT, but we've seen both sides of that. So, we're eager to have more outcomes there. It can have longer local control at a site that you're treating because you can deliver higher dose focally, so really treating cancers that might have been more radioresistant, thinking about renal cell cancers. So, that's another expanding case. And we've seen that it might extend survival. There's really compelling data from a phase 3 study, SABR-COMET, which showed for patients of all types — so mostly prostate, breast, and lung — that SABR for oligometastatic patients can extend survival if it's done to all the disease sites. There's now an actively enrolling phase 3 study, SABR-COMET-3. So, it's also good for retreatment of the same area that's been treated once or a nearby area, where with other techniques, you couldn't have really done that. I think as patients are doing better and living longer, this is a great tool for us. There are challenges, too. I think it can't always be done as quickly as some of our other tools like intensity-modulated radiation therapy (IMRT) or 3D, which we could turn around in hours to days. So, if there's a very urgent need, it might not suit that patient. It can take slightly more intensive resources, although this is changing. In radiation oncology, we're really a team. We have our therapists who are delivering the treatment on the machine, dosimetrists are planning the treatments, physicists may be planning and rigorously checking the quality and the machine characteristics, and we have our nurses. We need a good team with specialized expertise, and that could take time to develop. SBRT is widely available as a technique, I think becoming more and more so but not universally, though. So, of course, that matters in terms of who has access.
Lee: Well, that is exciting. I want to pick up on something you mentioned about retreatment. For our listeners, I want to clarify that SBRT can be used in previously radiated sites?
Elmore: Yes, it can. It's becoming a more common scenario thinking of patients I've treated in the last 2 weeks.
Lee: The concern we've always had about retreatment in a previously radiated site is long-term and short-term risks and complications, but then also long-term concerns about malignancies, secondary malignancies. It may be too early to know, but do we know much about the side effect profile of patients who are retreated?
Elmore: It's an excellent question. I think with newer techniques like SBRT, where there's less what we would call integral dose or scatter dose, we do tend to worry a little bit less about second malignancy risk for adults. And the second malignancy risks really take 10, 20, 30, 40 years to develop and are very small — on the order of maybe a 1% risk. Again, these are going to vary widely on technique and patient characteristics. Often if I'm treating someone who needs the treatment urgently, and we're thinking about a timeline of hoping for maybe 3 years, 5 years, that's not a big risk that I think about, though. I do think about some of the acute risks that you're also bringing up. We must be careful about when this area was last treated — that matters. If it was a couple of months ago, it's probably not a good candidate. But if it was 6 months, a year, sometimes it's been 10 years, then it can be a great candidate. Then, we really talk about what we know and what we don't know about side effects that could happen. We worry about spinal cord, we worry about lung, we worry about esophagus. So, those are things that we discuss carefully with our patients and with our physics team to help us make the right decisions.
Lee: When we're using SBRT for low-volume metastasis, are we thinking about that as a curative treatment or a palliative treatment?
Elmore: It's such a good question, and I don't think that this is one that has an answer. I think if you asked 10 different oncologists, you'd probably get 10 slightly different answers with maybe 50% of people saying, "Yes, this is curative," and 50% of people saying, "This is durable, but maybe we should still think about it as palliation." I don't think either is a wrong answer. I think cure is a slippery word in cancer care, no matter what stage of disease you're at. I think what we do know is that we don't have as much data in bladder cancer as we would like. There is a recent meta-analysis, the first author is Longo, and it's in Cancers in 2022 that took the six best studies that we have, all retrospective, for patients with — again, this was broadly defined per the trial — oligometastatic bladder cancer who got consolidative radiotherapy to the disease sites that they had. So, some SBRT, some not. There were 158 patients, and the local control varied widely, but it was mostly above 60%, sometimes near 100%. I would probably quote my patients somewhere near 70% to 80%. We're pretty good at controlling the local lesions. But what we really care about often is overall survival. So, these patients were decently well selected, and mostly 1-year survival was 80% to 90%; 2-year survival was lower, 30% to 60%. And toxicity was really low. Only five trials evaluated it but Grade 2 or higher toxicities in just three of the treatments. So, it's very safe if it's well selected, but our definitions haven't always been consistent of who has oligometastatic disease. And we need, I think, more prospective data.
Lee: You mentioned the importance of appropriate patient selection, which I think about. That is a critical aspect of treatment in the context of bladder cancer, even when we're using chemo, radiation, or trimodality therapy in patients with muscle-invasive disease. Who's the best candidate? If our listeners were thinking about who they should refer for SBRT, what would you say would be the ideal patient?
Elmore: We're always happy to collaboratively evaluate referrals, but the open trial that I talked about, SABR-COMET, I think those criteria suit any patient whom you'd think about referring. They're thinking about patients with one to three sites of disease, and I think some studies use one to five, and again, sites that are all amenable to some sort of ablative treatment, or thinking about a site that has progressed (oligoprogression). And really thinking there aren't that many sites that might be safely treated, and the primary disease has been controlled or is in the process of being stable; those are the patients I think about most, and then patients who have good performance status. For radiation oncology, we might think about Eastern Cooperative Oncology Group (ECOG) 2 or lower. We can treat people if they have reasons for ECOG 3. But just really thinking about people who might benefit if the sites aren't symptomatic, which could be another reason for referral for radiation. We're hoping that they're going to get some other benefit, whether that's staying on the medicine they're on, not having these sites bother them, or overall survival. I think that is very possible.
Lee: I know that we have more experience with SBRT for prostate cancer and kidney cancer, But as you think about applications in bladder cancer, are you aware of any trials that are ongoing or planned specifically in bladder cancer?
Elmore: Yes. In terms of ongoing trials, as of late May 2023, there is a European guideline that was produced. It is a consensus guideline modified Delphi method from the European Association of Urology (EAU), ESTRO, and the European Society for Medical Oncology (ESMO) all altogether. I think it's a great guideline, and one of the points was to say that we really need a definition so we can get these trials started. So, they're thinking about oligometastatic disease as a maximum of three metastatic sites, all resectable or amenable to stereotactic therapy. That was the consensus. And then pelvic lymph nodes are considered a site that's thought about differently. Also, there's no consensus on whether we should be using PET for staging in this space. I agree with that. I think it can be quite tricky. And then thinking about a favorable response to systemic therapy as a criterion for selection of patients, whether they are de novo oligometastatic disease, oligorecurrent, or oligoprogressive. It's a great definition to start with, and hopefully that helps us start these trials and really enroll patients with bladder cancer more on some of these trials that they would be eligible for.
Lee: We often deliver radiation therapy in combination with chemotherapy or another systemic agent. What are your thoughts about SBRT? Should that be delivered in isolation or in combination along with a novel agent? Does anybody have thoughts on that from other disease sites?
Elmore: Yes, and it really varies. I would say by site that we're treating and then by drug and mechanism and half-life and all these things. It is great that we have these kind of conversations as a multidisciplinary team, "Oh, I have started this drug. How do you think you would do SBRT? Do you think you'd dose reduce? Can we squeeze it in between cycles?" I think one of the nice benefits of SBRT is that with something like immunotherapy, there can even be synergy that's positive with SBRT. With our treatment planning, if we do that while someone's getting their cycle, we can often squeeze the treatments in, which are going to be five treatments or less by the US definition. We can squeeze those in between someone's cycles, so it doesn't cause them any treatment delay. Or with some drugs, if there's a little bit more of a potentiation effect and we're worried about side effects, there might be a break of a couple of weeks if we can get someone right back on that drug. We really talk a lot about sequencing, and I think more of these trials should include those combinations, where applicable.
Lee: You mentioned side effects, and I can't help but reflect on the fact that quality of life is a key driver for treatment for many of our patients. They're certainly weighing quality of life. And again, I know we have a smaller experience in bladder cancer, but perhaps in other organ sites, even prostate cancer, I'm wondering about your thoughts of SBRT to advance and improve quality of life.
Elmore: Absolutely. The literature on SBRT to the prostate has great quality-of-life data that I think has really led the way for us in terms of quality-of-life data in radiation oncology. But radiation side effects are so site specific. They're very local, so this is a little bit different. I think SABR-COMET-3 has really robust patient-reported and standard quality and side effects measures that they are collecting. I think those will not be perfectly analogous but very applicable if someone has treatment to a lung site. Regardless of the primary, the side effect profile is going to be more similar there. So, I think getting more quality-of-life data, particularly patient-reported outcome data, in the treatment of metastatic cancers with SBRT is really a space that is an active area of investigation for many of us because there's not as much data as we would like.
Lee: This has really been an informative conversation, and I've learned a lot about SBRT. I'm excited to hear that some trials are enrolling patients at this time, and certainly we'll look forward to those developing in bladder cancer. Given all that we've covered in this short time, do you have any points or highlights you'd like our listeners to take away?
Elmore: Yes, my takeaway is always think about your friendly neighborhood radiation oncologist, if you have one. We're very good multidisciplinary teammates in the care of patients. We love that. We love to be on the team early to think about muscle-invasive bladder cancer and to lend expertise. I think oligometastatic disease is really something where we've led the way and are always happy to explain, discuss, or evaluate a patient who you think might be a good candidate. SBRT is a safe and effective treatment in the right scenario for the right patient. It's something that I really love to bring to patients, because they are often so surprised at how easy it was. And I love that, there's not a better feeling.
Lee: Shekinah, thank you so much for being here today and for sharing your expertise.
Elmore: Thank you so much for having me. It was a pleasure.
Lee: Thanks for listening to our conversation with Dr Shekinah Elmore. There's much more ahead in the coming episodes, so be sure to check out the Medscape app and share, save, and subscribe if you enjoyed this episode. I'm Cheryl Lee for Medscape InDiscussion.
Definition and Diagnosis of Oligometastatic Bladder Cancer: A Delphi Consensus Study Endorsed by the European Association of Urology, European Society for Radiotherapy and Oncology, and European Society of Medical Oncology Genitourinary Faculty
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Cite this: Bladder Cancer SBRT: Meet Your Friendly Rad-Oncologist - Medscape - Jul 20, 2023.