Overall Burden of Advanced/Metastatic CSCC

Shubham Pant, MD:Welcome to this Targeted Oncology presentation entitled “Targeted Therapies in Advanced Cutaneous Squamous Cell Carcinoma.” Hi, I’m Dr Shubham Pant, an oncologist in Houston, Texas.

Precision medicine, or the tailoring of medical treatment to the individual characteristics of a patient, has come to the forefront of medicine in recent years. Today we are going to talk about the newest advances in the systemic treatment of metastatic or locally advanced, unresectable cutaneous squamous cell carcinoma, or CSCC. This shift in the treatment paradigm for a previously untreatable population has created a buzz in the dermatologic community. And today I’m joined by my colleague Dr Nikhil Khushalani, who is the vice chair for the Department of Cutaneous Oncology at Moffitt Cancer Center in Tampa, Florida.

Welcome Dr Khushalani, let’s begin.

Welcome, Dr Khushalani, to the show.

Nikhil Khushalani, MD:Thank you very much. It is my pleasure to be here.

Shubham Pant, MD:Great. So first tell me, this is kind of a rare disease, this advanced cutaneous squamous cell carcinoma. Can you tell us a little bit about it? Talk about the incidence and prevalence. How many cases are diagnosed early? How many cases are diagnosed late?

Nikhil Khushalani, MD:So essentially, this actually is not a rare disease, particularly when you look at the entire spectrum of what we now refer to as keratinocyte carcinomas, which primarily include cutaneous squamous cell carcinoma as well as basal cell carcinoma. It is certainly far, far more prevalent compared with the deadly one we normally know as melanoma. And previously these were called nonmelanoma skin cancers. Now they come under the basket term ofkeratinocyte, which is probably more accurate, primarily depicting their cell of origin. If one looks at a database analysis, primarily a claims database, over 5 million cases were reported in the year 2012.

Shubham Pant, MD:Five million cases.

Nikhil Khushalani, MD:Correct.

Shubham Pant, MD:Nonkeratinocyte, so basal cell and…

Nikhil Khushalani, MD:And squamous cell.

Shubham Pant, MD:And squamous cell, OK.

Nikhil Khushalani, MD:Because these can be picked up very early, there is a very high incidence related to sun exposure and occupational exposure. So over 5 million cases, or 5 million reports in over 3 million people who are individuals in the United States itself. And the incidence continues to rise. The incidence increases with increasing age and increases progressively with some cumulative sun exposure. So it is a common problem. What is less common, or one could even say is rare, is the development of advanced disease—advanced diseasebeing defined as nodal metastatic disease as well as distant metastatic disease with cutaneous squamous cell. And henceforth I’ll simply refer to this as CSCC. With basal cell, the development of distant metastatic disease is very rare. So most of the basal cells, when they become advanced, tend to be locally advanced disease.

Shubham Pant, MD:Are they just locally advanced or something and just keep on growing?

Nikhil Khushalani, MD:That is correct.

Shubham Pant, MD:OK, what about cutaneous?

Nikhil Khushalani, MD:So with cutaneous, there’s a small percentage of patients who can metastasize, and these tend to be very closely linked with the pathologic characteristics as well as the clinical phenotype of the individuals in whom this develops. So the pathologic characteristics that portend to higher risk for nodal spread, or distant metastatic spread, tend to be larger tumors. So the actual diameter on the surface.

Shubham Pant, MD:The size of the tumor?

Nikhil Khushalani, MD:The size of the tumor. The depth of the tumor. So those tumors that go down to invade the subcutaneous tissue have a higher risk of metastases. The poorly differentiated tumors have a higher risk of metastases. And 1 important feature is perineural invasion. Particularly for those who actually present with symptoms of pain, we always strongly suspect they have perineural invasion, and that is in itself a risk factor for local and regional recurrence as well. When patients have these characteristics, and you add in an additional clinical phenotype of this disease developing in an immunosuppressed individual, the classic presentation is those with solid tumor transplant recipients on immunosuppression. Those portend higher risk for both regional as well as distant metastases. For staging we previously utilized the AJCC [American Joint Committee on Cancer] staging.

Shubham Pant, MD:That is the classic TNM staging?

Nikhil Khushalani, MD:The classic TNM staging, but that was criticized because it didn’t match very well with prognosis. So a separate staging, a more clinically oriented staging, is the Brigham and Women’s Hospital staging, or the BWH staging, which primarily looks at those 4 characteristics pathologically that I mentioned: the differentiation, the size, the depth, as well as the involvement of perineural invasion.

Shubham Pant, MD:Let’s go back. So bydifferentiation, you would mean how well or poorly differentiated it is?

Nikhil Khushalani, MD:Absolutely.

Shubham Pant, MD:Sizemeans how big it is?

Nikhil Khushalani, MD:Large, correct.

Shubham Pant, MD:How large it is when you measure it?

Nikhil Khushalani, MD:Correct.

Shubham Pant, MD:And then your…

Nikhil Khushalani, MD:Depth of invasion.

Shubham Pant, MD:Depth of invasion. How deep it goes in something, like Breslow depth in melanoma?

Nikhil Khushalani, MD:Exactly. Very, very similar.

Shubham Pant, MD:OK. And then…

Nikhil Khushalani, MD:Perineural, invading the nerves.

Shubham Pant, MD:Perineural invasion.

Nikhil Khushalani, MD:That’s absolutely correct. So the incidence of regional or nodal metastases progressively increases as you have more of these characteristics in the primary tumor. And that seems to be more of a prognostic—or at least a more clinically relevant—staging system to help us define high-risk versus low-risk cutaneous squamous cell carcinoma. And of course, patients who are immunosuppressed, who are actively receiving immunosuppressive agents in the setting of transplant, or patients who are HIV positive with low CD4 counts or have other immunosuppressive diseases such as chronic lymphocytic leukemia are individuals who have a higher risk of developing more advanced disease.

Transcript edited for clarity.