Dr. Pauline Funchain:
Welcome to the ASCO Post Roundtable Series on Evolving Skin Cancer Management. I'm Dr. Pauline Funchain. I'm a medical oncologist at Stanford University. I co-direct the Skin Cancer Genetics Program as well as the Immunotherapy Toxicity Program.
Today, we'll be discussing the treatment of skin cancer with four patient cases. This is our second installment. This second installment will focus on the multidisciplinary management of cutaneous squamous cell carcinoma. So let me introduce you to case two. Mr. Smith is a 65-year-old man with a history of long-term sun exposure and multiple actinic keratoses. He presents to dermatology with a large aggressive lesion on his cheek that is 4 centimeters in diameter. The pathology on this lesion is a cutaneous squamous cell carcinoma. He also has a past medical history significant for CLL. And he is not undergoing any systemic therapy, he's just being observed.
So looking at this lovely lesion on his cheek, what treatment modalities would you consider? And questions here I would ask are, what kind of workup do you need? Do you need any workup, because he's immunosuppressed? Do you need any imaging? How extensive is this? Would you think about a sentinel lymph node biopsy? Is this something you go straight for surgery? Is there any thought for radiation? And does any of this change if this person has a history of immunosuppression or not?
Dr. Allison Vidimos:
Well, this is a high-risk tumor by location and size just to start. We don't know any of the pathologic features, but we would want to know the differentiation. We would want to know if there's perineural invasion. We'd want to know the depth of invasion. I'd do a good nerve exam just to make sure, if there's any perineural tumor. Admittedly, as we all know, there may be perineural invasion noted on path, but absolutely no symptoms on the patient's part, meaning their neuro exam is normal, so sometimes we're surprised by that. But in order to stage it, I would get that pathology information as well as a CT to look at the area to see if it is invading the parotid, to see what the neck nodes are doing. This is probably a T2b tumor at least; if it's invading deeper or if it's into bone, T3. So again, we want to adequately stage it to know what the next step would be.
Dr. Pauline Funchain:
And Dr. Zaba, is this something you would want to call in head and neck surgery for? Is this something... How far do you go as a dermatologist here and when do you start calling in other experts?
Dr. Allison Vidimos:
So it would depend what we saw on imaging. Because he is more high risk because of the CLL, we know that this has a higher risk of spread, a higher risk of recurrence after treatment, so we really want to pull out all the guns, so to speak, and get our ENT and rad-onc and med-onc colleagues on board. So this would be an absolute tumor board presentation about how to proceed. My guess is to say we would image, see where it is, do Mohs, clear it, and, depending on the nature of the wound, call in facial plastics for the repair. He might need a free flap there, for example. But the key thing is to really gather all the data and put everybody's minds together on how best to tackle it.
Dr. Pauline Funchain:
And Dr. Zaba, can you tell us about how that multidisciplinary works for you? Do patients see multiple doctors or do you do this at tumor board first?
Dr. Lisa Zaba:
I concur with Dr. Vidimos, this is a tumor board case. You're going to need imaging. You're going to need to see what the pathology shows, if there's perineural invasion. You're going to need to see if you can clear it with Mohs. ENT and plastics are probably going to need to weigh in as well as radiation-oncology may as well. Typically, surgery is the first option for these cases still, but everyone needs to be in agreement, and then see how things proceed.
Dr. Pauline Funchain:
Yeah, for something as... It seems so simple on the skin and on the surface, yet it's radiation oncology and Mohs and surgery, maybe facial plastics, maybe head and neck, so I can see that this gets complicated.
So I wanted to go through some very recent data, if I could share with you all for just a minute. At least in the oncology world, we're kind of figuring out where to put neoadjuvant approaches in squamous cell. So we haven't really had data on that before. And so as oncologists we're trying to figure out where can we place this, and I'd love to hear your guys' opinion on these data.
So just recently there was a publication on neoadjuvant cemiplimab, so an immunotherapy, a PD-1 inhibitor, and using that systemic therapy in the neoadjuvant approach, so prior to surgery giving immunotherapy. And not surprisingly, some sort of larger lesions had some good tumor shrinkage. We've seen that in the non-surgical setting with immunotherapy. And here, there is data showing a complete pathologic response rate of about 50-some percent. So we have some nice pictures and data, but we also know that there are AEs. And importantly, this was 79 patients, and 5 patients died on treatment. Now, whether that was because of treatment, in the text it really says that the majority of these were unrelated to treatment, but it is sort of something to think about because that is a rather high rate. Yes, an older population, but kind of a high rate of instances of death on a trial.
So with this new data, are you in your practices seeing a change towards doing any immunotherapy prior to surgery? Would you think about it for this guy? Where is this data now fitting into what you do?
Dr. Allison Vidimos:
We discussed it at tumor board honestly, and I think our biggest worry from a pure cutaneous oncology standpoint is making sure that the neoadjuvant therapy does not create discontinuous foci of tumor. So if it shrinks concentrically and the tumor's still in one contiguous mass, that is a good thing as far as then surgically removing it and making sure your margins are clear. I think one of our biggest worries, and we think about this with imatinib, with DFSP, for example, if you are trying to shrink a tumor prior to Mohs, are you separating islands of tumor that therefore could give you false negative margins?
But I think if you, again, keep an idea. We take a lot of pictures and we look at the size and extent of the photo. We've got imaging to tell us where the tumor started. So we pretty much know where our surgical field should be and, again, if there are any discontinuous foci, hopefully we are around them. So that's probably one of the things that we talk about repeatedly in tumor board.
Dr. Pauline Funchain:
So the discussion is there. Have you used it in this context yet?
Dr. Allison Vidimos:
Yes, we have, to shrink tumors.
Dr. Pauline Funchain:
Okay, okay.
Dr. Allison Vidimos:
And we've used it for recurrent squamous cell carcinomas that are in such tough locations, the periorbital skin, where surgery would necessitate orbital exoneration. So we're trying to save function as well as cosmesis. So that's probably the more common scenario for us to use the PD-1s.
Dr. Pauline Funchain:
Okay. How about you, Dr. Zaba, what are you guys seeing in terms of-
Dr. Lisa Zaba:
I mean, I am mostly a Merkel cell expert; however, I do sit in tumor board. And Stanford had a trial with neoadjuvant cemiplimab, and we typically have not used it outside of trial for neoadjuvant rescue.
Dr. Pauline Funchain:
Yeah, any thoughts about using this in the Merkel approach? I'm curious.
Dr. Lisa Zaba:
We have have absolutely. But not cemiplimab, because that's not approved for Merkel, but we absolutely have used the PD-1s for neoadjuvant and Merkel when it's not possible to clear something with surgery or radiation.
Dr. Pauline Funchain:
Right.
Yeah. I mean, certainly we can talk about this more, but neoadjuvant in a general cancer context is getting more interest. But I think many of us in oncology are just finding that it's really interesting data, it looks like it's the way to go, but we're not all jumping ship to neoadjuvant just quite yet. And it's interesting that it looks like it should be an easy decision, but it's, again, I think multidisciplinary. It depends on the case. It depends on a lot of things. So that is interesting to hear from both of you.
So I'm going to go on with sort of the alternate version of this story, because this is actually the version we see most of the time, which is that someone has already decided to do surgery. And then what happens is the pathology shows extensive perineural invasion. And then now you're stuck with feeling like somebody's really high risk now. They're immunosuppressed, and now you see poor pathologic prognostic features. And so then you feel like you want to throw the kitchen sink at the patient, right? So does this happen, do you refer to oncology, and what's typically the response?
Dr. Allison Vidimos:
Well, it depends if they've had radiation. I think in this scenario, this patient did have both. And at our tumor boards it would be discussed, there was a lot of perineural invasion, either a lot of small nerves or 0.1 and higher involved, which would make it high risk. Our radiation-oncologists are very good at setting their fields and accounting for that. And then we would follow them very closely with imaging and clinical exams about every 2 to 3 months to make sure that the tumor is staying away. Also, we do have the discussion with the medical oncologists about the PD-1s, because we kind of feel like we need a safety net.
Dr. Pauline Funchain:
Right, yeah.
Dr. Allison Vidimos:
Especially in a patient like this, you feel like you've gone all this way, and you want to put them across the line, and well.
Dr. Pauline Funchain:
Yes, I understand.
Dr. Allison Vidimos:
So again, it's discussing their comorbidities, seeing that they understand the side effects of the PD-1s and the length of therapy that they're committing to.
Dr. Pauline Funchain:
Yeah. Yeah, and what are you observing, Dr. Zaba, in terms of these conversations?
Dr. Lisa Zaba:
I mean, I agree, I think-
Dr. Pauline Funchain:
And you can extend it to Merkel cell if you'd like.
Dr. Lisa Zaba:
I mean, I think mostly the standard of care in squamous cell carcinoma with the perineural, I think this patient got the standard of care, which is radiation, to try and salvage it, extremely high risk. And I agree that the discussion is going to be with the medical oncologist in the event that this becomes metastatic or leaves the radiation site. And we would certainly discuss a PD-1 inhibitor, but the patient got managed with standard of care.
Dr. Pauline Funchain:
Yeah. So I hear both of you like, "This is standard of care, what this patient got," but you always feel like it's out there and, so can you use it because it's there already? And I feel like this keeps getting brought up in tumor board. I mean, I think we've seen this case multiple times in multiple tumor boards, and you can't not present it, and the answer is almost always the same from oncologists. It's like, "It's not standard of care."
And with that, I'd just like to point out that there are studies pending. So there are actually two studies that are looking at adjuvant immunotherapy in cutaneous squamous cell carcinoma, and there's one here with cemiplimab and another study with pembrolizumab. And neither of these studies have reported any preliminary data, so we really just have our standard of care, which is surgery and radiation, until we know that. And then, of course, these studies will come out and the results will be something that people will try to compare to the neoadjuvant study we just looked at. We're going to be stuck in a situation much like melanoma, not knowing which one is better. Although, some preliminary data in melanoma that potentially neoadjuvant may be better.
So thank you for that discussion. That answered a lot of questions for me and left a lot of questions open, I think, for all of us. So if I can summarize what I think we've talked about for cutaneous squamous cell carcinoma is that we do have to balance functional and cosmetic outcomes. And in some cases, it sounds like the functional outcomes or things that we are looking at maybe more important than cosmetic or vice versa, but certainly that is fair decision-making with the patient, that this in particular is a multidisciplinary approach, particularly in the immunosuppressed patients where there's a higher risk. And it certainly seems that in very aggressive cutaneous squamous cell carcinoma that there is currently and continuing to be a management evolution as we figure out where immunotherapy fits in the adjuvant/neoadjuvant space.
So thank you for that great discussion. That is the end of case two. Please see our other segments for further discussion about the latest in skin cancer or visit ASCOpost.com.
