How Patients With Advanced/Metastatic CSCC Present

Shubham Pant, MD:I know you’re a medical oncologist, but you workin a multidisciplinary setting, I’m sure with surgeons and dermatologists. Are most of these, like basal cell cancer, very common? Can patients get the cancer taken out with surgery, and then they’re good and can go along their way? So of these cases among cutaneous squamous cell cancer, of this 2 million, what percentage really present with advanced disease, where they actually come and see a medical oncologist?

Nikhil Khushalani, MD:That’s a great question. In some ways it’s hard to answer that question because of the frequency of both of these diseases—squamous cell as well as basal cell. There is no reporting required to a national registry. So for example, the SEER database, the Surveillance, Epidemiology and End Results Program, does not require reporting of these particular type of tumors there. So a lot of the data that we derive, particularly for identifying the development, incidence, and prevalence of this disease, are primarily from the medical claims database or the Medicare databases as well.

The vast majority of these patients, more than 95% of them, have localized disease. And thankfully the vast majority can be cured with simple surgery and a variety of additional modalities. It’s the 3% to 5% of them that can metastasize both to nodal basins—you know, regional—as well as to distant metastatic sites, most commonly the lungs, the liver, and the bones.

Shubham Pant, MD:OK. So the ones that you see are essentially the ones who have metastatic disease. Tell me, in your clinic, I’m sure you personally see quite a few cases.

Nikhil Khushalani, MD:Yes, we do.

Shubham Pant, MD:With your tertiary care center, you personally see quite a few cases?

Nikhil Khushalani, MD:Yes.

Shubham Pant, MD:So tell me, what is the main presentation of these patients who come in? Do they have a disfiguring lesion on their face when they come in? Or maybe they had an old surgery, and it’s been taken off and on scans they now have metastatic disease? What is the normal clinical presentation of a patient with metastatic or advanced disease?

Nikhil Khushalani, MD:It’s actually all of the above. So the vast majority of them, at least the ones that come to medical oncology as a direct referral or within our center, we function in a true multidisciplinary setting with surgical oncology, dermatology, radiation oncology—which plays a very important role in this disease—and certainly medical oncologists. We tend to get referrals for patients who have had progressive growth of their cutaneous squamous cell, regardless of the location. The most common locations tend to be the head and neck area, the face area, particularly the sun-exposed regions. In addition, we see them at sites of chronic ulceration, chronic trauma, fistula formation, and cutaneous squamous cell developing within that as well. So these are the typical presentations in which they’ve now grown beyond where the dermatologist can actually help them take care of it surgically.

We also get a large number of patients who present to us with palpable, nodal metastatic disease. And obviously biopsy demonstrates squamous cell. The first thing that we end up asking them is, “Did you have a cutaneous squamous cell at some point in that regional area?”

Shubham Pant, MD:Right.

Nikhil Khushalani, MD:The true incidence of distant metastatic disease is still being defined, particularly at presentation. There was a very recent publication inJAMA Dermatology—in fact, right hot off the press in November 2018—that tried to identify this through a registry in England, where they’ve actually now mandated supplying pathology reports for cutaneous squamous cell carcinoma to this registry.

So what they went back and looked at were the reports from 2013 to 2015, and essentially, they had a large number of cases, as one would expect, of cutaneous squamous cell carcinoma. But the true incidence of development in metastatic disease was roughly about 2% in those patients. It was lower for women and slightly higher for men. It was about 2.4% in men.

Shubham Pant, MD:So normally, when you see these patients, normally when they come to your clinic with metastatic cutaneous squamous cell carcinoma, tell me a little bit about that. They’ve undergone their surgical option, and they don’t have any more surgical options, but then the CLs are multidisciplinary. Now tell me, in your practice, how many of these patients are immune suppressed that you talked about solid tumor transplant, and after how long do they develop cutaneous cell carcinoma?

Nikhil Khushalani, MD:We’re not a solid tumor transplant center. We have a separate solid tumor transplant center in the city itself, so they have their own cutaneous screening program there. So a lot of the patients who come to our clinic, at least at Moffitt [Cancer Center], are the nontransplant patients. We do have a smattering of those who are associated with transplant. We see them more commonly with other immunosuppressive illnesses such as chronic lymphocytic leukemia.

Shubham Pant, MD:Got it.

Nikhil Khushalani, MD:But when you specifically look at the transplant literature, the patients who undergo solid tumor transplant — so this could be kidney, liver, heart, lung…

Shubham Pant, MD:Not like a stem cell transplant?

Nikhil Khushalani, MD:This is a solid tumor transplant, correct.

Shubham Pant, MD:Solid tumor transplant, got it.

Nikhil Khushalani, MD:Correct. These have an exquisitely high incidence of development of cutaneous squamous cell carcinoma. And the belief is that, number 1, they use immunosuppressive drugs in high doses that potentially can alter the immune surveillance of the body itself. And, therefore, precancerous lesions may actually then go on to develop cancerous lesions.

Shubham Pant, MD:But the immune system cannot grab them and take care of them.

Nikhil Khushalani, MD:Exactly. The incidence is very high. It can range as much as up to—on an average—100 times that one would see in the general population, much higher for cardiac and lung transplants. A little bit lower for kidney transplants. And these transplant patients, particularly in studies that have been done in heart transplant patients, at least a third of them will develop cutaneous squamous cell carcinoma in the first 10 years after their transplant. So it is an extraordinary problem and a disease burden in these recipients.

Shubham Pant, MD:So one risk is a solid transplant, but the other thing is areas exposed to light. So how does that work? Ultraviolet light, I’m guessing? How does it lead to the pathogenesis of this cancer?

Nikhil Khushalani, MD:So this is primarily a sunlight or ultraviolet B-related cancer. Primarily for CSCC, it is cumulative exposure over time. So it’s certainly seen in higher incidence in individuals with occupational exposure over a long period of time. For example, individuals who are working outside, like farmers or construction workers, who have not taken adequate sun protection. And if you sort of dial back the clock 2 decades or 3 decades ago, so the generation above us, they really did not use sunscreen or other sun-protective measures. And we probably didn’t know as well back then. Now I think we’re much smarter. So hopefully that incidence will decrease. Time will tell us if that indeed becomes the case.

But ultraviolet B essentially causes DNA damage in the keratinocytes of the skin. In individuals who are predisposed to that, the cells typically will not undergo apoptosis.

Shubham Pant, MD:They will not die.

Nikhil Khushalani, MD:They will not die. Exactly. The cells continue to grow and multiply. So they develop precancerous lesions, the most common being actinic keratosis. And untreated, that actinic keratosis eventually goes on to develop into cutaneous squamous cell carcinoma.

What ultraviolet light does primarily is produce multiple hits to these cells over a period of time, so there’s repeated DNA damage that occurs to these cells, and therefore it is cumulative over time. With diseases such as basal cell and melanoma, it tends to be the more intense damage that is associated, for example, with sunburns. So with the cutaneous CSCC, it tends to be over a long period of time.

Shubham Pant, MD:More chronic than more acute.

Nikhil Khushalani, MD:Exactly.

Transcript edited for clarity.