Cutaneous Squamous Cell Carcinoma Treatment

[Dr. Gopi Shah]
Let's say you have the patient, they come in with this defect. Let's say, the margins are positive. They're here to see you because the defect is big. We're still getting positive margins. How do you even start to think about-- how do you know where the margins were positive? Sometimes, it's hard the way the specimen may have been marked or the way the margins are set. The bigger the defect gets it's hard to know where to come back. How do you start to even, I don't know if the word map is correct, but orient yourself of where there might be tumor disease where we need to continue to excise?

[Dr. Gina Jefferson]
That's always a challenge when you're not the surgeon that's doing the primary resection. If I am doing the primary resection, it's easier to know where the margin's going to be positive for the skin. That does not hold true for the oral cavity, for example, where the 3D anatomy primarily of the tongue immediately changes upon excision. That doesn't hold true for the skin of the face. It's easier to mark your margins and you can go back and re-excise.

Now, the astute Mohs surgeon is going to provide the doctor to whom he refers a patient for positive margins, he's going to provide the map of where he has gotten positive margins and is just unable to clear the disease. In those instances, you will typically have a really good idea and ability to achieve margins. The problem is that oftentimes those locations are the eye. You're not trying to remove a patient's eye when the orbit itself, the globe itself is not involved. The mouth, when the lesion involves the cheek, you can go back and achieve margins and plan a reconstructive flap. The nose is also a little bit more complex. Generally, these locations, you can still do a wide re-excision and achieve clear margins without actually knowing precise location of the positive margin.

[Dr. Ashley Agan]
How many millimeters do you like for your margins?

[Dr. Ashley Agan]
The recommendations are about five millimeters. There have been studies, several studies, but I think there's one study out of UC Davis that demonstrated that there is a significant difference in disease survival if you achieve five-millimeter margins. We aim for that. Obviously in re-excision, it's hard to know that for certain, but your pathologist can tell you intraoperatively oftentimes in the area of concern where the positive margin was and the distance to the disease-free resection margin.

[Dr. Gopi Shah]
Tell us a little bit about adjuvant when-- all these patients assume that the tumor board, and maybe they've come in with their pathology, the slides have been read with your pathologist and you've discussed them then, or perhaps it's post the resection and you're re-discussing. When do you start considering adjuvant radiation? The other question I had about radiation was, are there patients that get primary radiation for cutaneous squamous cell?

[Dr. Gina Jefferson]
I'll answer that one first because that's easier. Yes, there are patients that are medically unfit or who choose not to undergo the surgery that we've outlined for cure. They'll choose to have radiation as their primary treatment modality. It's often something that patients with cutaneous squamous of the nose will undergo because you can maintain the natural nose, and so yes, primary radiation is definitely considered.

Now, adjuvant radiation is beneficial for patients that have regional disease, and then stage 3 and 4 disease are typically going to get radiated. People that have positive margins are going to get radiated. Patients that have extra capsular extension with their nodal disease are going to get radiation with chemotherapy for both of those instances, and now about tumor board.

Cutaneous squamous cell, I should say, non-melanoma skin cancers are by far and away the most common cancers in the United States. They have risen over 200% in the last 20 years. Because of those vast numbers, tumor registries don't include cutaneous disease except melanoma for tumor registry. There's no tumor board for most of these skin cancers, but we have a tumor board for skin cancer for the reason that we see so many advanced cutaneous diseases. We will discuss anyone that is basically sent to the University of Mississippi.

Now, my facial plastics partner probably does not because he will get early-stage disease that contributes to those high numbers of patients that are just going to do well because 85% of cutaneous squamous, we're going to do well no matter how you treat them, whether it's medical treatment or surgery, but for that 15% that we're discussing with highly aggressive disease, those patients will typically get adjuvant radiation and then chemotherapy, positive margin, extracapsular spread, there is exciting developments with respect to immunotherapy.

In 2018 the FDA approved cemiplimab for recurrent disease, metastatic disease, not curable by surgery, not curable by radiation. People are able to achieve, typically, a partial response over 60% of the time, but there have been instances where people have had complete response. That's interesting. In 2020, KEYTRUDA was also approved for the same things as well as locally advanced cutaneous squamous, again, not curable by surgery or radiation, again, achieving high response rates partially and even complete.

Last year, a new study came out, a multi-center study using cemiplimab in the neoadjuvant setting, and patients were able to achieve complete response pathologically. Neoadjuvant, they underwent three to four cycles of cemiplimab and then they had surgery and over 50% of these people had a complete response pathologically. That is truly exciting. Ongoing clinical trials are obviously pertinent here to identify just what patients are best suited for those regimens, what the regimen actually should be, and then the duration, of course, durability, and the response that's achieved.

There have been high response rates for KEYTRUDA with respect to lung cancer, for example, in this setting. I think it's exciting to consider that patients might be able to avoid debilitating functional aesthetic surgeries.