CHICAGO — In an educational session here at the American Society for Dermatologic Surgery annual meeting, Chrysalyne Schmults, MD, of Brigham and Women’s Hospital, provided an update on squamous cell carcinoma, including how to prevent patients from entering the high-risk category and available treatment options.
“One of the reasons I became a Mohs surgeon was to get to live in the happy world where we enjoy our 99% cure rate,” Schmults said. “I didn’t want to be an oncologist because I cry too easily. … I didn’t really want to see patients having really extreme disease. But in my first year as an attending at Penn, I had this lady with an extreme tumor and I was worried I wouldn’t be able to successfully control it.”
Schmults shared the details of her patient’s disease, to which she ultimately succumbed, with the audience, noting that it came as a surprise to her that some patients would die from their disease. It was this case, and others, according to Schmults, that were the impetus to develop a better staging system for high-risk cutaneous squamous cell carcinomas (CSCC). She submitted a grant to the NIH to explore improved predictive modeling and tumor staging in these patients, but one of the reviewers sent the grant back unscored, remarking that CSCC isn’t a disease worth studying because it “only kills 2,000 people per year.”
But cohort studies have shown that the metastatic rate is between 2% and 4% and the death rate is around 1%, which puts it “in the ballpark with melanoma for total deaths,” Schmults said.
Brigham and Women’s Hospital tumor staging for CSCC identified a group with a 20% risk for metastases and death from disease. Schmults and colleagues are preparing to publish data from a group with a still higher risk; currently, patients in the 20% risk group are mostly elderly and frail and often prefer not to undergo radiation or adjuvant systemic therapy for such a relatively low risk of death. “We need to figure out who’s a bit higher risk than that,” she said.
In the meantime, to prevent patients from entering the high-risk group, Schmults highlighted the following tips:
- Obtaining a clear Mohs margin is crucial; the 20% risk is cut in half with total margin control from Mohs.
- Radiologic surveillance improves risk for lymph node metastases; the risk is cut in half, possibly because more aggressive treatment was rendered earlier when subclinical disease was radiologically detected.
- Adjuvant treatment requires more investigation. Currently two trials are examining adjuvant radiation followed by anti-PD-1 therapy; results are anticipated.
Identifying patients whose disease has become unresectable is often straightforward if it’s obvious that surgery won’t eliminate all disease, according to Schmults. However, at times it’s not as obvious “especially now that we have anti-PD-1 therapy” she said. “That’s going to shift who we consider unresectable versus resectable because now we actually have another option to offer patients beyond multiple surgeries and radiation, and then rapid hospice if those fail. We now need to determine our surgical failure rate for different scenarios and see how that compares against a 50% response rate.”
The anti-PD-1 drug cemiplimab is currently the only FDA-approved option for cutaneous squamous cell carcinoma.
“So far, the decision making is simple. If someone is unresectable, they go on [cemiplimab; Regeneron, Sanofi Genzyme] and 50% will have a response. Complete responses are relatively rare, but it depends on how you measure it. A lot of these patients have maintained their response for well over a year. And in the melanoma world, we now have 5-year data with anti-PD-1 where these tumors haven’t progressed, and some of them have completely gone away,” Schmults said.
The question now, she said, is: How much do dermatologists want to own the care of this disease?
“Clark Otley once said, ‘If we want to own the disease, we need to own the data and we need to own the research’ … and that’s really true, especially for CSCC where dermatologists manage the majority of patients, including the high stage ones, and have done the bulk of the research in the field. I’m not saying all of us should run out and start doing IV chemo infusions, but dermatologists do these treatments in Germany and France and we can learn from them. If there’s a small set of you who are interested, this is something the dermatology community can start to think seriously about in the US, in conjunction with other specialists” she said. “… Combination therapies will probably involve combining anti-PD1 drugs with drugs that dermatologists will inject into tumors. So, dermatologists who treat patients with advanced CSCC will need to know a lot about anti PD1 therapy. There’s a whole bunch of work to be done that I think dermatologists should really be leading the way on. Let’s get going on it.” – by Stacey L. Adams
Schmults C. Emerging treatments for high-risk SCC. Presented at: American Society for Dermatologic Surgery Annual Meeting; Oct. 24-27, 2019; Chicago.
Disclosures: Schmults reports being an investigator and steering committee member for Regeneron’s trial that brought cemiplimab to market. She has no financial interest in Regeneron.