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Aimee Martin:  Welcome to the Oncology Sound Byte, a podcast produced by the Seattle Cancer Care Alliance designed to offer bite-sized audible oncology education from one of the top cancer treatment centers in the nation. I'm your host, Aimee Martin, a senior physician liaison at the Seattle Cancer Care Alliance, joined by my cohost, Dr. Jason Lukas, who's a medical oncologist and serves as the medical director of SCCA Issaquah. Welcome, Dr. Lukas.

Dr. Jason Lukas: Thanks, Amy. Great to be here.

Aimee Martin: Great to have you. And during this episode, we'll discuss metastatic kidney cancer and the Kidney Cancer Multispecialty Clinic or KCMC at SCCA. And it's a novel model that assembles a multidisciplinary team to treat this complex disease. With us to share more on this hot topic are two physician researcher leads of SCCA's Kidney Cancer Multispecialty Clinic. We have Dr. Scott Tykodi, Director of Kidney Cancer Research at SCCA and Dr. John Gore, Professor of Urology at UDub and SCCA. Welcome to the show.

Dr. John Gore: Thank you so much.

Dr. Scott Tykodi: Thank you very much.

Aimee Martin: Thank you for being here. And I'm going to go ahead and let Dr. Lukas take it from here and ask our first question.

Dr. Jason Lukas: So, John, Scott, thanks again for being here. It's a really great pleasure to interview you guys. And I just wanted to kick this off with just a short discussion from either of you about what the model is for the KCMC.

Dr. John Gore: Thanks, Jason. So, KCMC is unique opportunity for us to unite sort of all the specialties that are engaged in the care of the metastatic kidney cancer patient. So it addresses a gap that we witnessed as we tried to, you know, provide best care for our patients several years back where there was a fragmentation as patients would see Scott, they would see me as unique appointments, sometimes combined, but often, you know, days or weeks apart.

And so in order to try to put all of our brains together and figure out what the right approach is for each patient, we started the Kidney Cancer Multidisciplinary Clinic a couple of years ago. The providers that are involved in KCMC include a medical oncologist like Scott, a urologist like me and a radiation oncologist. And we have several partner radiation oncologists that. participate in KCMC. But it's also a great opportunity to show off some of the other services that are strengths at SCCA, like our genetics colleagues. There are several syndromes that are associated with kidney cancer and metastatic kidney cancer as well as colleagues in nutrition and nursing and care coordination. So it's just a way to bring everyone together to try to figure out what the best approach is for each patient.

Dr. Jason Lukas: I mean, it's a spectacular idea. I know we've all been in situations where you feel like you can't get in touch with the people you really need to get in touch with, then sometimes it gets as you pointed out fragmented. So I'm sure this helps speed up the process of cancer care for the individuals coming in.

And from your standpoint, gentlemen, we know what KCMC does for patients. What do you think, John in particular, is sort of the latest and greatest thing in kidney cancer care these days?

Dr. John Gore: I think I'm going to defer to Scott to talk about some of the latest and greatest in medical therapy and systemic therapy for kidney cancer. From a surgical standpoint, you know, kidney cancer, when we think there is a benefit to surgery, you know, we do our best to offer minimally invasive treatment options.

A big thing that is part of our decision-making process today is that how we think about surgery on the primary kidney tumor is different today than it was even three, four years ago. So three, four years ago, the standard was that when someone newly presented with metastatic kidney cancer, our default was often to try to remove their primary tumor. But with newer therapies being more effective and the ability of kind of that primary, what we call cytoreductive nephrectomy, to be associated with, for sure, improving their cancer outcomes, it's not as assured. And so now, oftentimes, we're doing this less in the upfront setting when someone is first diagnosed and we're thinking about it more, you know, six months, nine months down the road to figure out when it might be best positioned as an augment to their clinical care.

Dr. Jason Lukas: And that would be specifically in the metastatic setting or you're saying you have a person who comes in with small kidney cancer, and you're thinking about doing treatment ahead of time?

Dr. John Gore: That's different. So in someone with a localized kidney cancer, the options really are mostly surgical in nature. But in the metastatic setting, and this is really how we got started with Kidney Cancer Multidisciplinary Clinic, it used to be our very common practice that we would do upfront surgery to remove the primary kidney tumor. There's a historical precedent to that. Historically, there were these cases where, with removal of the primary, there was spontaneous regression of metastatic disease and that's what bore this idea of cytoreductive nephrectomy as an adjunct to systemic therapy.

And then there was a large trial that was published in the early 2000s, 2003 that showed that patients that got initial surgery followed by interferon had better survival than patients that got interferon alone. That's been updated. And a big part of that is that the systemic therapies we have are more effective. And now, we actually know that there is a harm to delaying systemic therapy. So an easy way to think about it is, you know, the systemic disease requires systemic therapy. And if we're putting someone through surgery first, that's going to impose a necessary delay in starting what they really need. And so now, we're often doing that more as a deferred operation.

Dr. Jason Lukas: Fascinating, because I don't know when you guys went to medical school, but the teaching was still take that primary out, as you pointed out, at any course in the disease. And I wouldn't be surprised that's still the teaching.

Dr. John Gore: When you go to our meetings and when you go to your updates on kidney cancer, most people are talking about the changing practice that frequently we are not doing initial cytoreductive surgery. Whether that has filtered down to sort of the community standard, you know, I can't speak to that. But when we're asked about it, that's our comment that more and more, we are not doing upfront cytoreductive surgery.

Dr. Scott Tykodi: Jason, just to throw a twist into the discussion. You know, my perspective. I think that question is one of the most challenging for both the urology surgeon and the medical oncologist is, are they sure they don't want to start with surgical therapy? And that's really the focus of having multiple specialties in one clinical program, is to have those conversations in real time and present the patient, the case for either yes or no surgery.

You know, there are patients with metastatic disease that have reasons they may benefit from having cytoreduction. They're having hematuria. They have a large thrombus in the IVC that's causing a lot of clotting and morbidity. They have a pain syndrome that maybe can be palliated by having the surgery.

And then the historical data as John alluded to was initially with an immunotherapy drug admittedly relatively impotent with interferon alfa. And the updates in 2018, the Carmena trials with a targeted drug, so it's changed drug class, and the current state-of-the-art is back to immunotherapy with checkpoint immunotherapy drugs.

And I'd have to say we're not a hundred percent certain what impacts cytoreduction will have. One of the recent updates of the ipilimumab nivolumab dataset, drawing attention to the patients that achieved complete response, shows that all of the patients that had a complete response had a cytoreductive nephrectomy. So zero patients had complete regression of their primary tumor. I think really again, ask the question is the surgical therapy part of the overall success of these patients?

So I think you've touched on, I think one of the most challenging questions that providers have, and I think it's a real service that we can provide. If I'm not sure what John's going to say. And I see a patient today and I refer them to John and he says, "You know what? We shouldn't do surgery. You should start with medical therapy." And the patient comes back to see me, well, there's probably two weeks for them to wait to see John. And then there's another week or 10 days to come back and see me. So a month has clicked by and nothing has happened and they're right back to square one. All of that discussion can happen in a single afternoon session when they're in KCMC. And so I think that streamline of care is also one of the real impactful features of the program.

Dr. Jason Lukas: And what’s the best way to get somebody to KCMC from your two standpoints?

Dr. Scott Tykodi: It's the same process an outside provider would have. It's a referral to our intake department and our intake teams have an algorithm to triage patients and offer them a KCMC appointment if they fit the profile, which is typically a patient that's newly diagnosed metastatic disease. But, you know, even patients with advanced local tumors where there's some question about the resectability or currently a patient that fits the profile of an active clinical trial that is looking at adjuvant therapy with nivolumab, a checkpoint inhibitor. So those patients straddle care between urology and medical oncology. The KCMC program is a wonderful venue where they can have conversations with both of those providers and really understand what the study is all about and see if they're interested. So the intake office, but outside providers can earmark patients specifically play into KCMC and ask for the patient to be seen in that venue. So it's at their discretion.

Dr. John Gore: We're always available for directed inquiries too, and that we can help direct the patient to KCMC as well.

Dr. Jason Lukas: And we'll work on your contact information at the tail end of this podcast. And one question, how far away do people come from typically? I mean, we've obviously got a catchment here that's quite large within the Seattle area. I've seen patients as far out as Spokane and as far South as Olympia. But I'm sure for this super specialized care, they must come from a lot farther away.

Dr. Scott Tykodi: Well, I think, yes, one consequence of the pandemic has been for the institution as a whole to become far more nimble in handling and offering telemedicine encounters to patients. And I think the benefit of that has been to open the door for this kind of consultative encounter for patients that come from great distance that don't have to come from a distance at all, they can be at home.

So we've done, for example, recently evaluated a patient that was in Alaska by telemedicine. We do Western Montana patients. We do Idaho patients. So the telemedicine option, I think, has made it an opportunity for patients to reach out and get specialized consultation from a referral cancer center at a great distance. But with the expectation they're likely to stay in their local care network and they'll just try and carry forward the game plan with their local providers.

I think the catchment for people seeing us in person is a little bit closer in to the Western Washington, Seattle-Tacoma area. But once again, whether it's a one-time consultation and taking the advice back to a local care team or patients that want to stay and receive all their care in our network, we certainly see both kinds of patients.

Dr. John Gore: We have some really great examples of that, where we have worked with the primary care team to figure out what clinical trials are available, what standard therapies are available and what resources are available to support patients locally.

We had a patient recently that we thought was best served by a clinical trial. And thankfully, the local site was actually a site for the clinical trial. So they were able to get that started locally. And then we were able to help the patient with their surgical treatment here and then send the patient back to Montana where they've continued on the clinical trial. So it's a great example of sort of working with our partners in the WWAMI region to care for a lot of these complex patients.

Dr. Jason Lukas: Impressive. I think that it's always, in my experience, hard to get trials out in places like Montana. But I guess the idea was they got started here in Seattle and then were able to carry it back with them.

Dr. John Gore: They actually got enrolled in Montana and then we did the surgery and then they maintained their enrollment in Montana.

Dr. Jason Lukas: Okay. Even better then. All right. Question for you, Scott, where do you see things in the metastatic setting? What's current right now for those oncologists out in Montana or Alaska? And where do you think things are going?

Dr. Scott Tykodi: I think right now I'm sure most providers are fairly comfortable with the variety of doublets that have entered the frontline space for kidney cancer. So doublets are us. Ipi-nivo lead the way. And so that's been with us now since I think 2018 with the FDA approval and then followed by multiple checkpoint immunotherapy plus targeted two-drug combinations. And we have the third of those that was approved earlier this year and a fourth expected based on GU ASCO data, the Clear trial of pembrolizumab and lenvatinib.

So very soon, we'll have four combination regimens plus ipi-nivo to choose between. So I think one of the challenges for docs is to, you know, decide which one. And I think there isn't a clear best. There's a lot of parity and so probably what people are familiar with is going to be fine and carry the day.

You know, we have a clinical trial portfolio and try and bring in things that we think are impactful for the field and for patients give them the opportunity, if they're interested, to take a look at that. And what we've had in the last year or so has been looking at triplet therapy, bringing a third drug into the fray. So we just completed-- well, completed the enrollment, the study's ongoing of ipi-nivo with, or without cabozantinib, the Cosmic trial. So a three-drug regimen in combination to ipi-nivo. And we're just poised to open a study that will be nivolumab-cabozantinib, so again an FDA approved doublet and bringing in a third drug, that is the NKTR-214, the modified interleukin-2, pegylated interleukin-2 drug by Nektar, so a triplet combination.

So I think that's where the field is at I think in terms of novelty, is looking at going from two to three. And, you know, in all honesty, a very standard oncologic approach and see if we can move the bar once more and build a triplet that's going to become the standard of care, but probably, you know, a couple of years out before those triplet studies read out and see where we stand.

Dr. Jason Lukas: And we'll see where the insurance company stand on treating people with all this uber-expensive medication.

Dr. Scott Tykodi: Yes, no doubt. You know, we haven't encountered troubles getting approval when we're operating the frontline space, that is the FDA approval for all of these regimens. But that being said, and I'm sure you're well aware, the infusional therapies are covered completely for patients, but the oral medicines often have copays applied.

And so that is a dilemma we sometimes face for patients is a high out-of-pocket cost, even though the drug is "covered." And our pharmacy services are fortunately equipped to look for patient assistance opportunities. We usually do pretty well, but that remains a challenge in the field is the widespread use of the oral medicines and the unpredictable expense the patient's bear.

Dr. Jason Lukas: Yeah, it's one of the conundrums I've seen too, particularly cabozantinib. I'm not sure how people would be expected to pay $3000 or $4000 or $5,000 copays a month.

But yeah, agreed. I think the infusional therapies are paid for, although I have bumped into insurance companies occasionally who said, "Well, I know it's an NCCN or I know the FDA has approved it, but we don't, in our insurance company, approve it." And so they can be a bit behind in terms of the national standard in my experience with it.

Dr. Scott Tykodi: Yes. That's a common phenomenon that shortly after new FDA approval, you submit a request and it's immediately denied as being experimental or off-label. And they simply haven't updated their pathways and algorithms. But I found that if you then write an appeal letter and simply point out that you're prescribing on-label for this treatment, you invariably get an approval. You've wasted time and effort, but the insurance company really can't deny a drug that's being offered on-label for a patient, but it's just that extra level of time investment and nuisance that comes with the new drugs. As time wears on and they become established, then you don't get that kind of unexpected denial.

Dr. Jason Lukas: Right. Well, fascinating discussion, gentlemen. Anything else you'd like to add before we take this out?

Dr. John Gore: I think, you know, from my perspective, you know, we've seen such a massive change in sort of the clinical care and the clinical paradigms for metastatic kidney cancer in the last, you know, two to three years. And so the expectation would be that this is a field that's going to continue to evolve. There are new trials that evaluated the benefit of cytoeduction, obviously new therapies coming on board. And I think that highlights again, the value of something like a KCMC, so that we can try to kind of maintain our finger on the pulse of the state-of-the-art for this complex cancer.

Dr. Jason Lukas: Absolutely. And I really appreciate that, because I know for myself as a community oncologist, it's hard to keep up with the latest things, especially when you're trying to keep up with the latest things in every other cancer under the sun. So I think that is much appreciated in the fact that we can have physicians from the WWAMI region or locally get in touch with SCCA and provide this service is really a wonderful thing for everybody within the region.

Dr. Scott Tykodi: Jason, I just want to highlight before we go. We do try and actually track and monitor what we think are quality metrics for the KCMC program. And so as we already touched on in the eyes of the patient, they have the opportunity to meet multiple providers in the same afternoon, so as many as three physician providers, surgery, medical oncology, radiation oncology, plus they have the option of meeting with the geneticist, plus meeting with nutritionist. So it can really be a packed afternoon where they can check a lot of boxes and walk away with a comprehensive game plan.

With outside providers, what you're getting besides the physician consultation from the therapeutic providers, you're getting a second opinion on radiology reports and the pathology reports. And we actually track the numbers of times that those reports are changed by the second opinion interpretation. And I think it's higher than you might think. It's between 15 to 20% of patients have a re-interpretation of their radiology or the pathology findings. And so, you know, sometimes it's fairly inconsequential, but there are numerous examples where that change clearly impacts the care of the patient.

For example, in pathology, we might change the histologic subtype. And so a patient that wasn't clear cell, that is declared clear cell is now eligible for clinical trials. Stage I or II patient that's re-read as stage III suddenly is eligible for adjuvant therapy and maybe an adjuvant protocol. So it's impactful. Maybe a missed call of sarcomatoid change that might change your thinking about what regimen you're going to offer the patient, because you want to really prioritize immunotherapy for sarcomatoid findings.

Our colleague, doctor that staffs KCMC clinic, separately has collected series of over 500 tumors reviewed at the university and recognizing that it's enriched for difficult cases because they were sentenced specifically for pathology review. But 24% of over 500 cases had novel finding or change in diagnosis by her review. And again, it spanned a range of things that were relatively inconsequential, but all the way to changing a benign to malignant diagnosis or vice versa.

So I think that element and also the radiology component, John and I can think of cases where a patient was declared metastatic disease and they weren't going to be offered nephrectomy. And we reviewed the scans and decided the findings that were considered metastatic we felt to be inconsequential and then pivoted and started with upfront cytoreductive surgery and just monitored the findings.

We had a patient I can think of that had metastatic disease, but they had completely missed a rib metastatic lesion where she was having pain. And so we could offer radiation therapy to the pain complaints.

So I think that is one of the wonderful features of referring a patient is not only are you going to get the therapeutic expertise and planning, but you're getting second opinion, radiology and pathology review as well. And I think that's really impactful and a little bit under the radar, I think, when you consider sending a patient in for the program.

Dr. John Gore: You know, you often think about radiology and pathology review increasing the complexity of the disease, but we've also had a number of really important cases where we've seen patients who are clinically staged as having metastatic disease that actually after our review, we felt had a localized kidney cancer, a potentially curable kidney cancer and so we were able to assuage that patient. We actually had someone who had an infectious disease in the lung, not a metastasis. And so we were able to help them out dramatically by doing a potentially curative cancer surgery.

Dr. Jason Lukas: Wow! Impressive. Well, I'm glad you guys are here serving the community. I mean, I can tell you from my standpoint again, as a community oncologist, I've certainly seen that where patients are judged metastatic and then they maybe have two separate primaries, got a patient like that in my clinic right now. And it just underscores the importance of having a second opinion on especially the most impactful thing that's going to happen to anybody in their lifetime, it's either getting married, having a kid or getting cancer probably. And so I think from my standpoint, it's always worth getting a second opinion. I know and, certainly from your perspectives, that's entirely clear.

Well, thank you very much, gentlemen. I think this has been a very insightful and instructive conversation for me and I'm sure for a number of people out there as well. Aimee, you want to take it out?

Aimee Martin: Definitely. Yeah. Thank you. Thank you so much to my cohost, Dr. Lukas and our special guests, Dr. Tykodi and Dr. Gore, for joining me today and thanks to our listeners for tuning into the Oncology Sound Byte.

To hear more, subscribe to the Oncology Sound Byte in your favorite podcast app. And to learn more about the KCMC along with other news out of SCCA, go to seattlecca.org/providerblog, and click subscribe.

Until next time. Thanks for listening and take good care.