A Closer Look at ASCO's Transoral Robotic Surgery Guidelines in HPV+ Oropharyngeal Cancer

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 Shepard, a Medical Oncologist, Director of International Programs for the Cancer Institute, and Co-Director of the Sarcoma Program at Cleveland Clinic. Today I'm happy to be joined by Dr. Jamie Ku, Director of the Head and Neck Robotic Surgery Program here at Cleveland Clinic. She is here today to discuss new ASCO guidelines on transoral robotic surgery for HPV-positive oropharyngeal cancer. So welcome to the podcast.

Jamie Ku, MD: Thank you, Dale, for having me again. Really excited to be here.

Dale Shepard, MD, PhD: Yeah. So maybe to start out, I gave your title, but what do you do here at the Cleveland Clinic?

Jamie Ku, MD: Yeah. So I am one of the head and neck surgical oncologists. I also do microvascular reconstructive surgery. So I pretty much help head and neck cancer patients throughout their treatment and recovery. I'm also, like you said, the Director of the Head and Neck Robotic Surgery Program, and so that is a main component of what I do, and my passion and research. And so yeah, that's my role.

Dale Shepard, MD, PhD: Very good. So we're going to spend some time talking about these ASCO guidelines for transoral robotic surgery. And so there's a lot of people might be listening in, different backgrounds. Maybe give us a little bit of an idea to start, when we think about these guidelines, what's the purpose of these guidelines in the first place?

Jamie Ku, MD: Yeah. So there's ASCO, which is obviously a large cancer oncology organization, society, that really looks at what are the needs in terms of the latest evidence and needs in terms of ambiguity or questions in terms of helping the cancer treatment teams decide how to treat cancer patients with the best, latest evidence. And so that's kind of where the needs are. And so once they determine an area or topic of need, then they put together an expert panel, and a guideline is formed over a few-year process.

Dale Shepard, MD, PhD: And so I guess, maybe so we can have a little bit of a look behind the scenes, what does that whole process look like? I mean, we see these guidelines. Everyone looks to them. We look to them for things here, and even at academic places for things we're not familiar with. It's guidance for our community partners and things, but give us a little bit of behind the scenes. How do we even come up with these in the first place?

Jamie Ku, MD: Yeah. So ASCO, again, they really have a great team that focuses on guidelines. And so there is a guideline expert that helps us, the clinicians, throughout the process. But essentially, they have chairs or co-chairs, and those are the leads. So I'm one of the co-chairs. And once that is selected, then we together come up with a panel of multidisciplinary experts. And once that panel is formed, then we do a systematic review of the literature, based on certain criteria and key terms. And then we review the literature, and then we come up with a set of questions that our guideline will focus on, and then a set of recommendations, and then we write it up.

Dale Shepard, MD, PhD: And then when you think about the questions, and we're going to talk about the actual guidelines in a minute, but just letting people know ... When you think about the questions, are these things that you as a group either agree and think everyone should know about, or disagree? Is there community input about, "Hey, we'd really like to know how to do ..." Something. How do the questions come about?

Jamie Ku, MD: Yeah. So when we say multidisciplinary team of expert panelists, it includes not just clinicians but also cancer survivors, advocacy representatives, even underserved representatives. So yeah, we do try to address all of those things as we are trying to put together what the focus of the guideline should be. So there is a wide range of input.

Dale Shepard, MD, PhD: Okay. Excellent. So we're talking here about these guidelines for transoral robotic surgery. One can imagine what that is, but give us an idea, what exactly is that and how it compares to more traditional surgical approaches?

Jamie Ku, MD: Yeah. So this is actually in the head and neck anatomic area called oropharynx. Transoral robotic surgery can be done for other parts, like around the voice box or the larynx. But focusing on oropharynx, these are the areas of the palatine tonsil or the base of tongue in the throat. And in general, these are difficult to access areas. And the traditional approaches are usually open approaches, where it requires large neck incisions, we go through the neck musculature, or we have to split the lip and the jaw to access these areas. So that usually means patients will require some length of tracheostomy tube, feeding tube, longer recovery time in terms of function.

However, the minimally invasive approach, which is the transoral robotic surgery, essentially uses a robotic system that introduces small surgical instruments through the mouth to access these difficult areas. It really helps improve not only access but visualization and the ability to resect these cancers with negative margins. So it's really ideally suited for these areas.

Dale Shepard, MD, PhD: And one could imagine that hospital stays would be a lot shorter and things like that.

Jamie Ku, MD: Exactly.

Dale Shepard, MD, PhD: How does that compare?

Jamie Ku, MD: Yeah. I mean, most patients do not require tracheostomy. I would say that's pretty rare. I would say in terms of temporary feeding tube, some patients do require a temporary nasal gastric feeding tube, but for a week or two at most. And then in terms of recovery, it's a lot faster because of the minimally invasive nature.

Dale Shepard, MD, PhD: What are some of the limitations to choose between procedures?

Jamie Ku, MD: So that's kind of what the ASCO guideline focuses on, is robotic surgery is exciting, it's cool, but these are surgical tools. And just like a knife or a cautery instrument, you have to make sure that you're using it for the right patient. And that's really one of the main reasons we endeavored on this ASCO guideline, is to help figure out what is the evidence telling us, and where there is no high quality of evidence, what are the experts' opinion or recommendations around patient selection and candidacy.

Dale Shepard, MD, PhD: And so, part of that patient selection and candidacy, the guidelines go through how you pick the patients, the right patients, the procedural ... When you should use the things you're talking about. So if we think about new patient, where do the guidelines come in and what are some of those recommendations?

Jamie Ku, MD: So, I think you can look at the guideline into the evaluation pre-treatment phase, and then there's the actual selection, especially for the surgeons evaluating the patients and the multidisciplinary team, and then what to do after surgery. So I think in terms of the initial evaluation, one thing we really emphasize in the guideline is the need for multidisciplinary evaluation. And that really, obviously, includes surgical oncologists, medical oncologists, radiation oncologists. But even beyond that, these patients need to be evaluated by the rehabilitative or supportive care therapists or clinicians. So speech-language pathologist is one of the main ones that are emphasized. They also need to be evaluated by dental oncologists, nutritionists, all of these people to help them make the best decision.

Dale Shepard, MD, PhD: And I guess just for perspective, patients with these oropharyngeal cancers, are most people seen in academic centers, or just because of the size of the group that's required, are there still people that maybe are seen more in a community setting?

Jamie Ku, MD: Yeah, I think there's a wide variety. I think certain patients, especially some of these patients, if they're aware of their potential cancer diagnosis or no, some of them do seek out tertiary center care. So we do see a lot of these patients. And obviously here at Cleveland Clinic, they are automatically put into multidisciplinary appointments. But out in the community, I think still a lot of these patients are being diagnosed by a community or comprehensive otolaryngologist, and then they get directly referred to community radiation oncologists and medical oncologists. So some of them do not even get really a robotics surgical evaluation upfront.

Dale Shepard, MD, PhD: So, thinking particularly about the robotic surgeries, when you do that initial baseline evaluation, what are some of the factors that would make for a good candidate?

Jamie Ku, MD: Obviously, part of what we do is a thorough history and physical examination. And as we're examining the patient, really, I'm not just looking at, okay, where is the cancer? How big is it? I'm also thinking about the patient's general anatomy. How's their mouth opening? What does their jaw look like? What does their dentition look like? How close is it to some of the surrounding critical structures like the soft palate? Is it mobile? Is it fixed? Is it coming out? Going inward? What is the relationship to the jaw, the voice box area? So these are all happening all at the same time as I'm examining the patient.

Obviously, we do get imaging to characterize the tumors. And in that, we also look at the deep extent to the pharyngeal muscles as well as all the deep blood vessels, including the carotid arteries. The parapharyngeal space is what it's called. So these are all the things that me as a surgeon has to evaluate to be able to figure out is this a patient for robotic surgery.

Dale Shepard, MD, PhD: Of all of those factors that you're taking in, are there some of these factors that are more often a reason to either decide to do robotic surgery or make people no longer a candidate? Are some of them either more common or just more of a limitation?

Jamie Ku, MD: So I would say in general, most patients who are best candidates, they tend to have smaller tumors in their oropharynx. So in terms of staging, T1, T2, all those. Select T3s can be candidates. Things that are more coming outward, exophytic, are better candidates. The ones that are going deep, probably you're going to be looking at a worse functional outcome after surgery. If it extends extensively into the soft palate, that's another contraindication for surgery because the functional implications of removing a good portion of the soft palate actually cannot be replicated even with the best of reconstruction.

And then the other one that commonly makes patients not the best candidate is actually not the primary tumor, the nodal status. So if patients have extensive nodal disease, for example, with obvious evidence that it's coming out of the capsule of the lymph node or extranodal extension, or they have disease in both sides of the neck, low neck, retropharyngeal lymph node, these are all indications that they're going to need chemotherapy. So these are not the ideal candidates.

Dale Shepard, MD, PhD: Right. Makes sense. Tell us a little bit about the importance of HPV status.

Jamie Ku, MD: So HPV status in oropharyngeal cancer is how we even decide how to stage these patients. So it's really very critical in the diagnosis. Patients who have HPV-related oropharyngeal cancer, that's pretty much majority of what we see these days, and that is the reason why there's an increasing rise in the incidence of oropharyngeal cancer. And so most patients we see do have HPV-related cancer. And the other really significant factor is patients who have HPV-related cancer actually have excellent prognosis. So up to 90, 95% survival outcome in five years, versus 50 to 60% for HPV-negative, which is traditionally more related to tobacco and alcohol use.

Dale Shepard, MD, PhD: And so, a lot of that shift, is it because we've had better lifestyle choices?

Jamie Ku, MD: Exactly.

Dale Shepard, MD, PhD: And our education efforts are helping?

Jamie Ku, MD: Yep. They are helping. So in general, most head and neck cancers, for example, in the voice box and other areas that are related to tobacco, they are decreasing in terms of incidence. So I think all of those efforts are helping. But in terms of the virus, there are different risk factors. And so those are the things that, so far, is still increasing mainly in developed countries, but as we all know, there is a vaccination available that is cancer-preventative vaccination for our teenagers. So highly recommend everybody get vaccinated.

Dale Shepard, MD, PhD: From a guideline standpoint, what was the consensus on HPV testing, and testing to make sure that people have the correct status?

Jamie Ku, MD: Yes. So all patients with obviously oropharyngeal cancer or cancers that are not obvious in the head and neck area but have metastatic squamous cell cancer in the neck, all of these patients should have HPV testing. And our recommendation in the guideline is actually doing HPV testing specifically, not just p16 testing, which is a surrogate marker. Doing additional HPV testing, whether in the form of PCR or FISH, is critical. And the reason for that is there are growing evidence showing that the concordance rate of p16 and HPV testing is not 100%. And so up to 10% of the time, they don't test positive for both. And there may be different prognostic implications based on the status of p16 and HPV. Yeah.

Dale Shepard, MD, PhD: Important to know that that's correct from the start.

Jamie Ku, MD: Yes.

Dale Shepard, MD, PhD: Specifically, with the transoral robotic surgeries, from the standpoint of that procedure, what's the difference if there's HPV positive or negative? How do you approach patients?

Jamie Ku, MD: Yeah. So in general, we don't see as much HPV-negative patients anymore, in general. However, patients who have HPV-related disease tend to present with smaller cancers in the throat and sometimes more noticeable lymph node disease, so more advanced nodal disease. Whereas HPV-negative cancer patients tend to present with advanced tumor staging. So it's almost rare to see HPV-negative or pharyngeal cancer patients. And when we do, they tend to have more extensive involvement in the primary site. So they are not always surgical candidates through the transoral robotic surgery.

However, if we have a patient who has HPV-negative disease but have small tumors that can be surgically resected, those are candidates for transoral robotic surgery. So from that perspective, I think a lot of the selection criteria still can hold.

The only difference is, for HPV-negative cancer, we do think more in terms of intensification of treatment, not de-intensification. So the role will not be necessarily so we can minimize their treatment. Sometimes we're trying to maximize treatment.

Dale Shepard, MD, PhD: Okay. Makes sense. A lot of the discussion, we're talking about new onset disease and how we initially approach. What's the role for recurrence of tumors?

Jamie Ku, MD: So, in general, when patients have recurrence, it also depends on what their treatment history was. Did it recur after surgery? Radiation? Those are usually the backbones of the treatment for these. So that also will play a role in terms of whether they're candidates for transoral robotic surgery. But I think if they do recur where transoral robotic surgery is feasible, they are candidates, but sometimes if they've been radiated, you have to counsel them that recovery time could be longer in terms of healing.

Dale Shepard, MD, PhD: And so, I guess just to clarify, if patients originally had a traditional open procedure and they have a recurrence, they still might be a candidate for the transoral surgery?

Jamie Ku, MD: Yes. Yes. So it depends on what that open surgery was, but in general, if they recur and it's a small primary where the surgery can remove all of the cancer with a negative margin without causing significant functional dysfunction, that they could be candidates. Again, if they've had radiation, again, that takes a multidisciplinary discussion, whether or not they would need any kind of reconstruction or have some delayed healing process. But they are candidates, yes.

Dale Shepard, MD, PhD: From a guideline standpoint, is there anything else that was a significant recommendation?

Jamie Ku, MD: I think we covered the part about the emphasis. I think here at Cleveland Clinic, we have a very well-incorporated team, including speech-language pathology, nutrition, dental oncology. But in some of the other practices out there, I think one of the things that we do try to set out is to try to get these people involved early in the initial evaluation phase. A lot of these patients should get a baseline swallow study to determine how their swallowing function is. And that may impact the recommendation in terms of whether or not you pursue surgery versus non-surgical.

Dale Shepard, MD, PhD: When you think about these guidelines, typically, what's the uptake? People have a lot of different sources of guidance. Certainly ASCO, being a really large organization, has a lot more clout, I guess. What have you seen in terms of people coming in to see you for initial evaluations, talking to colleagues? Is this being adapted pretty easily?

Jamie Ku, MD: Yeah. I think in general, these are very practical recommendations. I mean, there are some things that are a little bit more controversial or to be determined, and so I think there is a lot of excitement about the guideline. Again, I think depending on where you practice, what kind of setting, whether it's in a large institution versus smaller regional hospital or in the community or international, I think some parts of the guideline will probably apply to you, but more than the other. But I think just in general, try to get a multidisciplinary evaluation. If you don't have access to a surgical oncologist who is an expert in transoral robotic surgery, I think either referring them out or having another surgeon who has some idea of the indications or contraindication, I think that is important to discuss upfront. And so yeah, I think it's a really good guideline for an unmet need area.

Dale Shepard, MD, PhD: So I guess just a final question. It's always interesting when you get groups of multidisciplinary people together, and you sometimes catch this in advisory boards and things. What was the biggest surprise? What were you most surprised by? Something you thought you maybe just took for granted, and then there was some debate among the group. Was there anything as you talked through how to treat something that you're like, "Wow, I didn't even think that would be an area of controversy"?

Jamie Ku, MD: No. It's not really a surprise, but I think it's more of a call for need, is when you're doing a systematic review and you're looking at surgical candidacy. And when you're getting down to the details, like I was mentioning earlier, there's not phase three clinical trial determining whether or not cancer that's near the soft palate is a good candidate or not, right? So I think a lot of what we do in surgery is not always based on high-level quality of evidence.

Dale Shepard, MD, PhD: It's a lot of nuance.

Jamie Ku, MD: Exactly. But at the same time, I think there is a lot of surgical oncologists in the clinical trials arena that are really being principal investigators in large practice-changing clinical trials. So I think that's the other really exciting thing, is there are lots of good clinical trials in the head and neck cancer field that are either resulted or ongoing. So I think that's the other side of what is exciting.

Dale Shepard, MD, PhD: Yeah. Well, it's interesting to hear about the guidelines here, interesting to hear a little bit about how these things even get put together. And so appreciate you being here for your insights.

Jamie Ku, MD: Thank you. Thank you for having me. And everybody, go out there and read the guideline.

Dale Shepard, MD, PhD: That's right. And follow them.

Jamie Ku, MD: Yes. Yes.

Dale Shepard, MD, PhD: All right. Thanks a lot.

Jamie Ku, MD: Thank you.

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