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Cutaneous Squamous Cell Carcinoma Treatment

Author Julia Casazza covers Cutaneous Squamous Cell Carcinoma Treatment on BackTable ENT

Julia Casazza • Feb 2, 2024 • 35 hits

While surgical resection represents the mainstay of cutaneous squamous cell carcinoma (SCC) treatment, uses of radiation and immunotherapy continue to expand. Surgical resection is useful in a variety of scenarios, from lesions cured by excisional biopsy to those requiring reconstruction with free tissue transfer. Head and neck surgeon Dr. Gina Jefferson of the University of Mississippi recently joined BackTable to educate listeners on the contemporary management of this common condition.

This article features excerpts from the BackTable ENT Podcast. We’ve provided the highlight reel in this article, but you can listen to the full podcast below.

The BackTable ENT Brief

• Negative margins are a prerequisite to surgical cure of any malignancy. When treating cutaneous SCC, surgeons should strive for negative margins of 5 millimeters, as this confers survival benefit.

• Reconstructive plans must account for disease characteristics, patient priorities, and patient body habitus. Reconstructive options following cutaneous SCC resection span the entirety of the reconstructive ladder.

• Radiation is used to treat stage 3 and 4 disease, patients with positive margins after surgery, extracapsular extension, and nodal disease.

• The uses of immunotherapy for SCC treatment continue to expand. Two anti-PD-1 monoclonal antibodies are approved for SCC that cannot be treated with surgery/radiation. Current research aims to increase the applications of these treatments.

Cutaneous Squamous Cell Carcinoma Treatment

Table of Contents

(1) The Importance of Negative Margins in Cutaneous Squamous Cell Carcinoma Treatment

(2) Considerations for Challenging Reconstruction in Cutaneous Squamous Cell Carcinoma Treatment

(3) Radiation & Immunotherapy for Cutaneous Squamous Cell Carcinoma Treatment

The Importance of Negative Margins in Cutaneous Squamous Cell Carcinoma Treatment

When resecting cutaneous SCC, negative margins of five millimeters increase the odds of survival. Margins should be taken from excised specimens. Dr. Jefferson prefers the use of marking paint to identify margins in her OR. In cases where patients with positive margins are referred by their Mohs surgeon, operative notes should clearly orient surgeons to the location(s) of any remaining cancer.

[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.

Listen to the Full Podcast

Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction with Dr. Gina Jefferson on the BackTable ENT Podcast)
Ep 135 Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction with Dr. Gina Jefferson
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Considerations for Challenging Reconstruction in Cutaneous Squamous Cell Carcinoma Treatment

Formulating a reconstructive plan requires consideration of wound size, potential functional impairment, patient body habitus, and possible exposed bone. Collaboration with oculoplastics is warranted for lesions found on the eyelid or in the sulcus between the eye and the eyelid. In cases of nasal SCC, prosthetic noses provide the best results after total rhinectomy. Patients with treatment plans including radiation should defer reconstruction until radiation therapy is complete, where possible.

[Dr. Ashley Agan]
As far as talking about the challenges of different reconstruction when you're having to, we can take this site by site, but you mentioned the eye a lot. Having skin cancer around your eye is really challenging. Can you unpack that more and dive into what you're thinking about when you're thinking about having to reconstruct that area?

[Dr. Gina Jefferson]
As far as the primary disease, you could have-- I've had patients with skin cancer in that sulcus between the eye and the nose. That one's challenging because of the lacrimal system. Do I need to stent the lacrimal system or somehow reroute it? Full-thickness eyelid, that requires reconstruction. Even for me, I will consult the oculoplastic surgeon to help participate in that reconstruction.

Then, of course, the more lateral you get, inferior lateral, I should say, any reconstruction is going to involve scar formation. Anything that's going to contract or pull the eyelid lower, that requires some kind of lateral canthoplasty to help prevent that. Again, I don't have any reservation in consulting my oculoplastic surgeon to help with that function and aesthetic appearance.

[Dr. Gopi Shah]
I think that's where the multidisciplinary and the partnership is very helpful.

[Dr. Gina Jefferson]
Love our colleagues of all specialties-- neurosurgery, ophthalmology.

[Dr. Ashley Agan]
For the noses, for example, sometimes if it's a significant portion of the nose, you may also be thinking about a prosthetic versus how good can I make it look with a free flap and some grafts because you're replacing cartilage, and giving it structure, and you need a mucosal lining. It's soft tissue and all these things versus having something that's a prosthetic, which has to be taken on and off. How do you think about those types of things?

[Dr. Gina Jefferson]
I think in my hands, I have done both ways of reconstructing before radiation, reconstructing after radiation. Either way, when you're dealing with partial or total rhinectomy, those patients are going to need radiation. Radiation is going to impact your reconstruction. It's probably better if you reconstruct after, but patients want something to just go out of the house. I think the best results aesthetically when you're dealing with a total rhinectomy are typically with a prosthetic nose.

I don't think it's obvious to patients that sometimes leaving a portion of the nose in those instances is less cosmetically pleasing than just simple removal of the entire nose because of the nasal subunits, just the ability to achieve the natural appearance, and contour, and the lighting impacts how you appear. The prosthetic nose in total is often a very reasonable means of achieving reconstruction, if you will.

When the full-thickness involves the nasal sidewall, for example, and/or the ala you can typically achieve some modest form of function as well as aesthetic appearance by flaps, the workhorse flap being the paramedian forehand flap with cartilage for recreation of the nasal ala. They can also reconstruct the strut of the nose if needed as well, the columellar strut. I think it all depends on the nasal defect, but when you're approaching subtotal, there's no such thing as subtotal rhinectomy. Just the entire nose probably should go when you’re considering both resection as well as reconstruction.

Radiation & Immunotherapy for Cutaneous Squamous Cell Carcinoma Treatment

Radiation constitutes a useful adjunct or alternative to surgery in patients with cutaneous SCC. Primary radiation is an option for those medically unfit for surgery or patients with nasal squames who are unwilling to undergo rhinectomy. Adjuvant radiation is used in cases of stage 3 or stage 4 disease, positive margins, extracapsular extension, and nodal disease.

Uses of immunotherapeutic drugs for cutaneous SCC continue to emerge. Cemiplimab and pembrolizumab – both anti-PD-1 monoclonal antibodies – are approved for recurrent/metastatic SCC not amenable to surgery/radiation. Treatment with these drugs can be indefinite, and response to therapy is assessed using Response Evaluation Criteria in Solid Tumors (RECIST) applied to imaging. The most common side effects of anti-PD-1 immunotherapies are diarrhea and fatigue.

[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.

Podcast Contributors

Dr. Gina Jefferson discusses Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction on the BackTable 135 Podcast

Dr. Gina Jefferson

Dr. Gina Jefferson is a professor of otolaryngology and the chief division of head and neck oncologic and microvascular surgery at the University of Mississippi Medical Center in Jackson, Mississippi.

Dr. Ashley Agan discusses Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction on the BackTable 135 Podcast

Dr. Ashley Agan

Dr. Ashley Agan is an otolaryngologist in Dallas, TX.

Dr. Gopi Shah discusses Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction on the BackTable 135 Podcast

Dr. Gopi Shah

Dr. Gopi Shah is a pediatric otolaryngologist and the co-host of BackTable ENT.

Cite This Podcast

BackTable, LLC (Producer). (2023, October 17). Ep. 135 – Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction [Audio podcast]. Retrieved from

Disclaimer: The Materials available on are for informational and educational purposes only and are not a substitute for the professional judgment of a healthcare professional in diagnosing and treating patients. The opinions expressed by participants of the BackTable Podcast belong solely to the participants, and do not necessarily reflect the views of BackTable.



Cutaneous Squamous Cell Carcinoma (CSCC): Evaluating Risks & Navigating Complex Surgical Reconstruction with Dr. Gina Jefferson on the BackTable ENT Podcast)


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