Treating Retroperitoneal Sarcoma

Podcast Transcript

Dale Shepard, MD, PhD: Cancer advances at 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 Shepard, a medical oncologist here at Cleveland Clinic overseeing our Taussig Phase I program and co-director of sarcoma care at Cleveland Clinic. Today, I'm happy to be joined by Dr. Nate Mesko Center Director of Orthopedic Oncology and co-director of Sarcoma Care at Cleveland Clinic and Dr. Dan Joyce, a surgical oncologist in the Digestive Disease and Surgery Institute here at Cleveland Clinic. They're here today to talk to us about a team approach to treat retroperitoneal sarcoma. Welcome Nate. Welcome Dan.

Nathan Mesko, MD: Thank you.

Daniel Joyce, MBBCh: Thank you very much.

Dale Shepard, MD, PhD: Maybe to start off, tell us a little bit about your roles here at Cleveland Clinic. So Nate, you want to start?

Nathan Mesko, MD: Thanks for having us, inviting us to be part of this. Some may ask why I'm here for a retroperitoneal sarcoma discussion. I spend a lot of time with many of my surgical colleagues. I think one of the unique attributes of what sarcoma is, is that it picks virtually any place in the body to present, whether that's inside the cranium, all the way down to the toe and anything in between. The pelvis and the abdomen and the spine area, kind of the mid section is a very high yield place where lots of surgeons have to work together in order to take care of these complex problems.

I become involved in that scenario, especially in pelvis sarcomas and retroperitoneal and then also just working with our team helping lead the sarcoma program here at Cleveland Clinic. It's an honor and a privilege to be able to get to work with all of these world class physicians, both on the medical side, as well as on the surgical side.

Dale Shepard, MD, PhD: Very good. Dan?

Daniel Joyce, MBBCh: So I trained initially in general surgery here at Cleveland and then pursued a fellowship in complex general surgical oncology in Roswell Park in Buffalo, where a lot of the focus was on complex, rare and unusual malignancies, which the sarcoma family falls into. I think as Nate pointed out, this is a multidisciplinary specialty. A lot of the culture here at the Clinic focuses on organ-based diseases. That's how our institute models are set up. And I think that works very, very well for the vast majority of diseases, but for sarcoma, I think we really go be beyond all of that.

So in our Tumor Board I think we have representatives from almost every institute, where we have the Orthopedic Institute, Digestive Diseases, Thoracic, Cardiovascular, and all of that. So I think we all very much think about this as a disease, not as an organ-limited thing. So as surgeons, I think we kind of figure out what the map looks like and what specialties we need there to take care of these diseases.

Dale Shepard, MD, PhD: That's absolutely true. When we talk about retroperitoneal sarcomas, so we have a diverse group that may be listening in, so let's just sort of define what we're talking about. So Dan, maybe you could tell us, what is a retroperitoneal sarcoma? Where's the retroperitoneum? What kind of cancers are we typically thinking about there?

Daniel Joyce, MBBCh: So what I often say to patients, it's the back of the abdomen, and typically, these sarcoma arise from the glue that holds us together. So the commonest entity would be a liposarcoma or sarcoma of fatty tissue, and they can come in a various spectrum of well-differentiated liposarcoma where the problem really is just a local issue in the back of the abdomen and really a surgical issue, maybe with radiation to occasionally ice the cake.

Then we can have much more aggressive variants where not only do we have a local problem, but we have to think about a systemic issue with metastatic disease, with high grade dedifferentiated liposarcomas. The probably next most common would be a leiomyosarcoma, which is a tumor of smooth muscle. They can arise from numerous locations, up to and including the vena cava and the vasculature. So again, highlighting that we'd just done a big caval sarcoma last week, where we worked with vascular surgeons who rarely if ever, encounter malignant disease. And that's a key case where we need their help, but they heavily rely on us to kind of police them from an oncologic standpoint and they appreciate that and we need their skills as well.

Dale Shepard, MD, PhD: So Nate, we've talked already about the wide range of disciplines involved, the number of surgeons maybe urologists involved and vascular surgeons and you, as an orthopedic surgeon. Tell us a little bit about how this all comes together. How do we coordinate care as a program put together sort of a group that can work so well together? How do we do that?

Nathan Mesko, MD: Yeah, I think one of the first keys is, we all got to enjoy working with one another because there is a lot of communication and there's a lot of sacrifice, frankly, on behalf of each of us to make something happen, to coordinate a lot of schedules, to herd cats, so to speak.

When a patient arrives, they come oftentimes with a diagnosis, a lot of anxiety, and maybe some scans to look at. And we start the process by identifying the correct disciplines. I think with retroperitoneal sarcomas, there is a lot of potential anatomy involved, including the intestines, including the vasculature that Dr. Joyce talked about, including the spine or some of the nerves and muscles, including the pelvis bone. That is anatomy that, while it's all in the same area, there are certain specialties that are more comfortable with certain aspects of that.

So, it honestly, from a team approach is more fun to work together with your colleagues. I think it's safer and more efficient and decreases the risk of complication to work with your colleagues. But that doesn't just start when you get to the operating room. There's oftentimes multiple weeks, if not a month or more of planning, of coordinating, of testing, of discussing at our Tumor Board.

I think the penultimate area where we really kind of finalize and fine tune that plan is at our multidisciplinary sarcoma board, where our radiologists present the pictures, our pathologists present the tissue that we've sampled to prove the diagnosis. Then we discuss as a team with the experts, from the chemotherapy aspect, from the radiation aspect, from the pathology, radiology and surgical aspects to come up with a fine tuned plan that will best treat the diagnosis given, in the location given for the most optimal outcome.

Dale Shepard, MD, PhD: So Nate, you mentioned something that I think oftentimes is missed and that's really the importance of pathology review and making sure that that's really... If someone's coming and they've had a diagnosis, is that really the diagnosis? So as surgeons, you guys are removing things, you're not choosing chemotherapies, but Dan, tell us a little bit about how the pathology view and actually knowing what that tumor is before you go in to deal with it, how important is that?

Daniel Joyce, MBBCh: I think that's critical and I think one of the highlights of our program is that the conversation about the patient begins long before they arrive here. So we have a wonderful cancer answer line that essentially assembles all of this information so that when these patients arrive on site, if their imaging is not complete, that really within the course of a morning, we can really get to that place where we can start the decision-making process. We like to have the slides on site beforehand. And many of these patients have been two, three months going around, searching for a diagnosis. And I think coordinating all of that ahead of time. So we have a wonderful back office staff that make all of this possible that puts us in the position to make the diagnosis.

I agree. The pathological review is essential. Many times the patient are told that it's a spindle cell neoplasm. We recently had a patient who was referred in with a recurrent GIST in the abdomen, and it turned out on reviewed here and after next generation sequencing, it was in fact, a rare synovial sarcoma. That has absolutely tremendous difference in the patient's treatment.

The patient had been on inappropriate imatinib or Gleevec for a long period of time when in fact, a radical different approach was required. So it can be night and day and certainly kind of a major impact on survival as well.

Dale Shepard, MD, PhD: We have a large center. We have a lot of disciplines involved. Who's an ideal patient? So Nate, who would be an ideal patient that we should see compared to someone that has a small mass in their abdomen? Should we see anyone with a retroperitoneal sarcoma? Can some of those be handled more in the community. Give some guidance on who should be referred here.

Nathan Mesko, MD: Yeah, I think I'd like to hear Dr. Joyce on this as well, but from my perspective, I think sarcoma is because it's such a rare entity, because the quotes would suggest in many practices that a physician who is not specialized in sarcoma doesn't have a specialized practice or niche in practice, will only see one or two of these in their entire 30 year career. So it's hard to maintain a semblance of expertise and awareness of even recognition before the treatment process starts if you're doing this on a very, very irregular basis.

I think one of the things with retroperitoneal masses is that unlike extremity masses, surgeons are less tempted to go and operate on many of these masses without knowing what they are. On extremities, on arms, a bump right underneath the skin, the surgeon may say, "Oh, that's easy to take out. That's not really going to harm the patient," and then have a surprise when the pathology comes back and what they thought was a fatty tumor wasn't actually a fatty tumor.

In the retroperitoneum, if somebody's having symptoms and imaging suggests that there's a mass there, I think that's a very low threshold for a community practice to refer that simply so that they don't have to deal with the headache of all the items that need to be checked off in order to appropriately get this patient to the optimal treatment. Send it to a center that is able to do this every single day and let us handle those headaches. Let us handle that plan and the whatnot.

So we're always willing to communicate, to partner and I very often will call the referring providers just to get a story and to keep them in the loop in terms of like, "Okay, thank you for the referral and here's the plan moving forward." Many times, especially if they need radiation or they need systemic therapy, we'll often partner with their local providers as well. We help quarterback things, but we need partners that can help us locally.

Dale Shepard, MD, PhD: Dr. Joyce?

Daniel Joyce, MBBCh: I would agree and I think as we have alluded to, no physician is an island for this disease. So for example, a surgeon may be comfortable doing a certain operation, but they may not have the radiology backup to help take care of the postoperative complications. They may not have a radiation oncologist that's comfortable in treating sarcoma since it's so rare.

The other point is, not everyone needs an operation. So many times we see patients with masses that do in fact turn out to be benign. There are even some masses that can be caught on PET scans, like schwannomas that do not need an operation. So sometimes we're actually providing reassurance and just surveying a patient. So it's not that everyone has to have an operation. It can be figuring out who in fact does not need an operation.

I think also, there are lots of other things other than sarcomas that can turn up in the retroperitoneum, germ cell tumors that may never need a surgeon and need medical therapy. So I would say, I think that that initial biopsy and diagnosis and workup, that probably the most important decisions are made outside of the operating room. So unless that you have that whole team to help you out, which is a pretty unusual, you need to be at a pretty big center to have absolutely everyone to make those decisions, I would say if there's any doubt at all, we're happy to see them and many times we send them right back to you, but it's often a well worthwhile visit for the patient and we can often provide reassurance. If it's something bigger and more involved, we obviously are delighted to take care of that as whoa. So

Dale Shepard, MD, PhD: Dan, you mentioned radiation. We're going to get back to that in a second, but just carrying on, we've talked about sort of patient evaluation and care prior to even them coming here for an evaluation. We've talked about the intraoperative, all the people involved. Nate, we've talked about this in program meetings before.

What about the ability to take care of really complex patients oftentimes sort of in that perioperative setting? So I think that's another strength that we have is, if people have complex medical needs, it's not just getting through the surgery, but then how do you get past the surgery and back home in a meaningful way. So can you maybe talk about that a little bit?

Nathan Mesko, MD: Yeah. I think surgery, obviously if surgery is necessary, which oftentimes it is, there's a recovery involved. And most oncologic surgery requires some kind of sacrifice of collateral anatomy to get the cancer out. Our number one goal in the vast majority of these cancers is, to get the cancer out cleanly. Times that's not possible. Occasionally, we'll do surgery to help with symptoms and not necessarily aimed at cure, but the majority of these patients, we are attempting to cure to the best of our ability.

So when the patient wakes up and they're recovering and the surgery is successful from... we removed the cancer and we did it with a clean cuff of tissue surrounding it, the patient may still have recovery of their bowels, sometimes of their bladder. They may have loss of nerve function. And that's where the long term follow-up by not only the surgical teams, but outside of cancer, the physical therapy teams. We have an excellent physical medicine and rehabilitation team that oftentimes patients can, especially if there's nerves involved or the spine is involved with these retroperitoneal sarcomas, the patients can go and spend some two or three weeks of a pretty intense rehab in order to fast track their ability to become confident and learn to adapt with their new kind of baseline.

Then once they become comfortable with the recovery, and we've kind of navigated through the waters of potential complications, then there's the whole surveillance aspect that's also necessary. You know, I think the majority of our work years after the surgery is following these patients who have been diagnosed with this rare type of a cancer, because there's a potential, it could either grow back in the same place, or we could find it somewhere else and getting regular frequent exams and scans is absolutely essential to the most optimal outcome.

Dale Shepard, MD, PhD: Very good. Dan?

Daniel Joyce, MBBCh: I would agree with that. And I think the other specialty that we oft forget about are palliative care. We often include those very early on. Some of these patients come with very large masses. They can come with a large component of neuropathic, chronic centralized pain, even prior to surgery, and they can need ongoing support, not in the sense of end-of-life care, but in terms of control of pain.

A lot of these patients have anxiety. It's a traumatic process going through, whether it be radiation, chemotherapy, a large operation. And I think that group as well, provide tremendous support to these patients where Nate and I often, we are like plumbers or carpenters. We take things out, put them back together, and we're very compassionate people, but we're constantly thinking about margins and getting things out.

That's appropriate, but the palliative care folks, they leave that to us, they leave the medical oncology to you and so on and so forth, and they focus on these patients as whole people. Sometimes it may be just something like insomnia that to me, I'm like, "Oh, well, you've healed perfectly fine from surgery," but that could be the single biggest issue to the patient. So I think all of that big family of support really helps these patients resume as much as normal life as possible.

Dale Shepard, MD, PhD: Tell me a little bit about radiation therapy and sort of the issues related to radiation and retroperitoneal sarcomas.

Daniel Joyce, MBBCh: So how much time do you have? So for radiation is an adjunct to good surgery. I think the ultimate goal is a margin-negative resection for a sarcoma, regardless of the location in the body. But by virtue of the location of the retroperitoneum, there are a lot of structures that we can't cut out or shouldn't cut out. So historically, we've used a lot of radiation to treat the margin, almost always in the preoperative setting as the tumor itself kind of acts as a spacer to keep the bowel away, which is quite sensitive to radiation.

There was a recent randomized controlled trial, the STRASS trial that really was a negative trial with respect to preoperative radiation for the treatment of sarcoma. Unfortunately, like a lot of our data in sarcoma, it's quite heterogeneous and the story hasn't been quite put to bed in terms of, I often think about the role of radiation preventing a local recurrence. Where would that recurrence be? What would the morbidity of the recurrence be? If it's sitting under the liver tucked away, that's fine. If it's sitting on top of the femoral nerve, that's a different recurrence.

So we here still have a... We use a fair amount of radiation. I think we've backed off based on the trial, but we talk about it in our multidisciplinary tumor board. We also have an interest in a newer hypofractionated regimen. That means where patients just get five days of radiation, rather than a historic 25 fraction or five week protocol. And we're currently studying that on a trial here at the clinic. I think that's something that's exciting and we'll be interested to see what our data shows. So radiation is not gone from the retroperitoneum, but I think we're a little less liberal with it nowadays.

It depends a little bit on the histology as well. If there's something high grade that's going to have a metastatic potential, something like leiomyosarcoma, often they don't recur as much as a well-diff liposarcoma, which often we can manage surgically anyway.

So it's a complicated area and I think the STRASS trial has been very helpful, but it certainly hasn't answered the question definitively.

Dale Shepard, MD, PhD: As with most trials in sarcoma.

Daniel Joyce, MBBCh: Agreed. And I think the key thing is you have to say, does my patient fit this trial? Can I apply this trial to my patient? And that's not always true in every case.

Dale Shepard, MD, PhD: Yeah. Taking a step back, Nate where are the gaps? Where do we need to make improvements in management of retroperitoneal sarcomas?

Nathan Mesko, MD: Well, I think even just beyond retroperitoneal, I think sarcoma in general. I think collaboration is one of the biggest gaps that we see, especially in the surgical world. A lot of institutions, a lot of really well-known institutions that are really good at what they do, are doing it on an island in a lot of respects. And to the fact that it is such a rare disease, it could take literally decades to get appropriately powered numbers from a single institution to actually answer a question with the utmost confidence when it comes to appropriately-done research.

I think the fact that Cleveland Clinic is working, kind of extrapolating what we've done with extremity sarcoma and trying to take five weeks of radiation therapy and squish it into a biologically equivalent five-day course and get the tumor out, literally a couple months before we historically would do it, is a big deal, but again, the numbers are going to be limited.

And the goal of something like this is to give kind of a taste to the sarcoma world to say, "Hey, here's a pilot. Here's something that we've tried." It certainly is not inferior, dare I say, maybe even better in some respects. Why don't we actually partner with each other? You know, we have all these big meetings that we'd like this international and national meetings that we talk about sarcoma and say, "Okay, let's take the beginning results of this and let's actually create a partnership of all these large institutions around the world, which the STRASS trial is a good example of that in Europe and continue to take that to the next level.

I think surgical techniques, one of the other things that I would love to be able to use is, to figure out a way that we can see intraoperative margins live. That sometimes can be very difficult with some of these infiltrative tumors where you can see and feel the actual mass, but there may be microscopic tentacles. In some way, they either have some kind of a dye injected or virtual augmented reality, or some kind of a technology that can give the surgeon the absolute utmost confidence that, "I have gotten all of this, not just what I can see and feel with my eyes, but the microscopic areas," can really, I think, enhance what you're able to tell a patient in terms of what needs to be sacrificed to get this out and hopefully decrease the risk of having to deal with recurrences down the road.

Those are two items that come to mind.

Dale Shepard, MD, PhD: Dan, any gaps for you.

Daniel Joyce, MBBCh: I would agree. I mean, I think it's all about trying to do a safe operation in difficult circumstances. And I think our outcomes have improved dramatically over recent decades due to advances in imaging. So I agree with Nate that taking imaging to the next step with potentially virtual reality and things like that, that really I think all of us try and plan the exact operation in our head prior to ever making incision. This is something that has to be pre-planned. And of course you have contingency plans, but I think hopefully, if we can move the needle just a little bit there, we can even increase the precision even more.

Dale Shepard, MD, PhD: Very good. Well, Dan, Nate, appreciate your insights and being with us today.

Daniel Joyce, MBBCh: Thank you.

Nathan Mesko, MD: Thank you very much.

Dale Shepard, MD, PhD: To make a direct online referral to our Taussig Cancer Institute, complete our online cancer patient referral form by visiting clevelandclinic.org/cancerpatientreferrals. You'll receive confirmation once the appointment is scheduled.

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