Targeting PD-1 in Non-Melanoma Skin Cancers - Episode 1

An Overview of Non-Melanoma Skin Cancer Epidemiology

July 8, 2019

Shubham Pant, MD:Welcome to thisTargeted Oncologypresentation titled “Targeting PD-1 in Non-Melanoma Skin Cancers.” Hi, I’m D. Shubham Pant, an oncologist at The University of Texas MD Anderson Cancer Center in Houston, Texas. Today, we are going to jump right in and discuss the newest advances in the systemic treatment of advanced, non-melanoma skin cancers, including cutaneous squamous cell carcinoma and basal cell carcinoma.

Please join me in welcoming my colleague, Dr Michael Migden, dermatologic oncologist and Mohs surgeon in the Department of Dermatology and Head and Neck Surgery at the The University of Texas MD Anderson Cancer Center. Welcome Dr Migden.

Michael R. Migden, MD:Thank you.

Shubham Pant, MD:Dr Migden, tell me, as the first thing, what is a dermatologic oncologist? Can you explain that to us?

Michael R. Migden, MD:Yes. So, as you know, dermatology covers a wide range of conditions. A subset within dermatology would be cutaneous malignancies. And we have to remember that both basal cell and squamous cell carcinoma—non-melanoma skin cancers, the most common ones—are definitely primary cancers of the skin.

Sometimes people think that dermatologists are pimple poppers and do little small things with small skin cancers. But actually, this is a primary cancer of the skin, so I’m committed to treatment from those that can be tiny lesions that can be destroyed to those that need Mohs surgery or excision, through larger tumors that can no longer be treated by surgery or are inappropriate for surgery. And that’s where systemic therapy comes in.

Shubham Pant, MD:Tell me a little bit about Mohs surgery. Whom is it used for? Which patients is it appropriate in?

Michael R. Migden, MD:Mohs surgery has appropriate use criteria, and this is established to make sure that we’re not overusing Mohs surgery. Most of the tumors on the head and neck can qualify for Mohs surgery. Below the neck there’s more stringent criteria, including size, such as 2 cm or other more aggressive features. Mohs surgery differentiates itself from standard excision in that we check 100% of the margins, the true contact area between the specimen removed and the patient, and we map this out.

Also, the surgeon is the pathologist acting on the case, and we actually read the slides, and based on our colors marked on the tissue that we see in the microscope, we go back and use those same colors on the map to mark out where the tumor is. Then we keep going back to the patient to get more until all of the tumor is clear. But not only that, Mohs surgeons typically do cutaneous reconstruction. I reconstruct more than 99% of all the cases that I treat, so there’s that aspect. And comparing Mohs surgery to excision, for example, Mohs surgery checks 100% of the margin, so we can start with a very small margin because we’re checking thoroughly. Excision checks less than 1% of the true margin with the patient, so it has to have a bigger surrounding margin of normal skin to compensate for that.

Shubham Pant, MD:So Mohs surgery is much more complicated, has a lot more input from the surgeon. So you’re a dermatological oncologist, pathologist, plastic surgeon?

Michael R. Migden, MD:We’re dermatoplastic reconstructive surgeons, so that’s quite a different thing. There are things we don’t do, like large free flaps. But in terms of the standard linear repairs and other flaps and grafts that are appropriate to do under local anesthesia, we do those.

Shubham Pant, MD:Tell me how common this is. What is the incidence of basal cell cancer, cutaneous squamous cell cancer of the skin?

Michael R. Migden, MD:Due to the lack of these cancers in the SEER [Surveillance, Epidemiology, and End Results] and other registries, the exact numbers of these are estimates. It’s estimated around 5 million cases per year of basal cell and squamous cell carcinoma.

The estimates show that the ratios used to be about 20% squamous cell and 80% basal cell carcinoma. Recent in-depth analysis shows that it’s approaching 1:1 because the population is aging, and squamous cell occurs more in an older population. And if that trend continues, there’s a possibility that squamous cell could outnumber basal cell in the future. But right now, it’s close to 1:1. So we’re talking about estimates for squamous cell, 1 to 2 million cases per year, probably closer to 2. And then basal cell, 2 million cases, but some people think it’s more like 4 million cases.

Shubham Pant, MD:Wow. What are the key factors that differentiate these 2 cancers, squamous cell from basal cell? You said one is advancing age, they’re more prevalent with squamous cells. What are the other key factors that separate these 2 cancers?

Michael R. Migden, MD:They’re both typically mostly ultraviolet-induced cancers. That’s how they’re joined by a common thread. The squamous cell carcinoma, as we said is an older population, but other things like immunosuppression. Immunosuppression preferentially increases the risk for squamous cell over basal cell carcinoma.

These 2 cancer types look different. They appear differently. Basal cell carcinoma tends to be a somewhat translucent papule, nodule. It can look otherwise like a scar, but squamous cell carcinoma and the precursors to that are scalier and crustier typically than basal cell carcinoma. Of course, there is some crossover between these 2 appearances. And in fact, some tumors are basal cell that have squamous differentiation, and there are some squamous cell carcinomas that have basal-like differentiation.

Shubham Pant, MD:So it can get complicated.

Michael R. Migden, MD:Yes.

Shubham Pant, MD:How many are early resectable and how many are locally advanced that cannot be resected by, let’s say, Mohs surgery?

Michael R. Migden, MD:The exact numbers are difficult to determine because the lack of inclusion in registries. Nobody knows how many squamous cell carcinomas are locally advanced. We do know estimates of death from squamous cell carcinoma, and one source says they range between 4,000 and almost 9,000 deaths per year, and then the Skin Cancer Foundation quotes 15,000 deaths per year from squamous cell carcinoma. And of course, those would be the advanced type that would include both locally advanced and metastatic.

Shubham Pant, MD:What are some of the risk factors? You mentioned ultraviolet light. Are there other risk factors for squamous cell or basal cell carcinoma?

Michael R. Migden, MD:The typical ones are the ultraviolet-induced. We talked about the role of immunosuppression, say solid organ transplant or other reasons for immunosuppression, that would increase the risk. There are genetic syndromes that can increase the risk of non-melanoma skin cancers. One particular condition for basal cell carcinoma is Gorlin syndrome or basal cell nevus syndrome, where these patients, due to a genetic aberration, can form hundreds and sometimes thousands of basal cell carcinomas, so it’s very challenging to treat.

Transcript edited for clarity.