Systemic Treatment of Metastatic Cutaneous Squamous Cell Carcinoma - Episode 6

Systemic Therapy for Advanced CSCC: Patient Selection

October 31, 2018

Michael R. Migden, MD:I think the indications that go with a drug approval are patterned after the inclusion and exclusion criteria from the studies of which the approval was given. Therefore, I do not think about patients as unresectable because I don’t like that term. There are some aggressive surgeons that say they will operate on anything, but for patients that aren’t surgically appropriate, meaning they’re not good candidates for surgery and that can fall in the category of having failed multiple prior attempts. It could be in the category of there’s a low confidence in obtaining clear margins due to the extent of the disease. It could be in the category of there are going to be consequences, and those consequences could be a high morbidity, so functional loss to the patient, and even significant disfigurement. So that would be a case where, for example, you could have loss of all or most of a facial appendage, such as an ear, or a nose, or an eye. And yes, you might be able to get it out completely with surgery, but at what consequence? At what price to the patient? And those cases, if you can have a systemic therapy that has a chance at either completely treating that tumor or making it much smaller, that’s important rather than just proceeding with something that you know is going to be a big price for the patient in terms of a consequence.

The candidate that is appropriate for Mohs [micrographic surgery], would be one where removal of their cutaneous squamous cell carcinoma is likely. In other words, you shouldn’t start Mohs surgery unless you believe you have a good chance of removing it in its entirety. It’s not really a debulking procedure. It’s a curative surgery. Most of the time, we can determine this by measuring the lesion, palpating the lesion. There are cases where because the history, the size, the pathology report mentioning higher risk features where we need the results from imaging, which would include either CT [computed tomography] and/or MRI [magnetic resonance imaging], rarely PET [positron emission tomography]/CT. And to know that what we’re talking about is a contiguous tumor, that is having a high probability for success, in terms of having a negative margin.

Then when we are looking at patients in terms of removing their cancer, we also want to think about reconstruction. As a Mohs surgeon, I do the vast majority of my own repairs. The majority of them, even some more advanced reconstructions are certainly reasonable to do in the Mohs surgery setting. There are times though that Mohs surgery may still be the appropriate tumor extirpation technique but combining with a free flap which would be performed by plastic surgery after the Mohs surgery is complete. That can also still be a highly effective treatment for that patient.

There are times when we assess a patient clinically. We palpate the lesion and notice that it is fixed and bound down to deep structures, especially to bone. And surgeons, for the most part, don’t cut any bone where we think about sending out to have a larger en bloc resection that can be done by head and neck surgery. Sometimes Mohs can collaborate with head and neck surgeons by clearing the peripheral soft tissue and then leaving a clear peripheral margin and a central tumor that the head and neck surgeon can remove en bloc and get a much deeper resection and take out bone or muscle as is necessary.

There are times when these advanced tumors don’t look like a good candidate for Mohs at all, or it’s something about the patient’s case—their morbidities, whatever—would be better off just having it all done with head and neck surgery. And then when we have advanced tumors from head and neck surgery, it’s frequently combined with radiation as there is a belief that radiation therapy combined with larger en bloc resections by head and neck surgery provide a survival benefit. For any of those patients that become the more advanced cases, even ones that will be pursued with surgery, having a consultation with medical oncology is important as well in the event that surgery with or without the radiation is not enough. The belief is that systemic therapy should be added. So that’s a time to include a medical oncologist.

Now, from my perspective as being a dermatologic oncologist, I believe that multidisciplinary care is the best thing for the patient anyway. My baseline is to get all the disciplines involved, myself. These are for advanced cases, of course—myself, head and neck surgery, radiation oncology, medical oncology, and then in some cases, plastic surgery involved, and then have a consensus discussion at a multidisciplinary conference and determine really what is the best care for the patient. I like doing larger Mohs surgeries. Not all Mohs surgeons like to do the large cases. I like doing them as long as they have a high chance of a complete resection or it’s combined, as I said clearance with Mohs and a central larger resection by head and neck surgery. As long as it’s appropriate, we continue with that plan. Now, when you think of people that aren’t good surgical candidates at all, where surgery is not going to obtain a clear margin, and surgery plus radiation is still not to be a good option for the patient, then get the medical oncologist and dermatologic oncologist together and see what other options might be available.

I am sent patients from head and neck surgery, and sometimes from medical oncology, and radiation oncology when it looks like surgery with or without radiation, even larger surgeries are still not a good option for patients. They’re not going to clear the tumor, the ability to perform radiation in some areas has a lot of morbidity. These are things that are causes for patients to be sent to me for consideration of systemic immunotherapy. They could also be sent to medical oncology. As a PI [principal investigator] on a phase II international registration study, I accept and treat these patients. I think that there’s room for both medical oncology as well as dermatologic oncology, both in terms of either being a prescriber or part of this multidisciplinary care that continues to manage the patient.

The question of having adjuvant postoperative radiation is one that is a work-in-progress in terms of what the best plan for the patient is really. The belief is that postoperative radiation for larger planned resections, such as head and neck surgery, will provide a survival benefit. There is some data for that in similar cancers. The data [are] not widespread, in terms of exactly what that benefit is, but the belief is that there is some. When somebody should get radiation, I leave to the radiation oncologist for their assessment based on their experience, their data that they are an expert on. And there are many cases where they believe radiation should be performed postoperatively and some when they don’t. I don’t make the judgment in advance. If it’s something that I think is going to have a larger surgery, such as a head and neck surgery, I would recommend they at least get that evaluation, a consultation with a radiation oncologist.

In terms of medical oncology, it’s that same algorithm of deciding whether you think that surgery with or without radiation is enough. And, if you think that it’s not going to be, then adding a systemic agent is something to think about. When you think about having surgery followed by systemic therapy, such as an anti—PD-1 [programmed cell death 1], that would be an adjuvant use of anti–PD-1, that’s an area of investigation, but there’s no real data on that at this point. So, there’s nothing I can go by and say that based on risk factors of a patient that either has Mohs surgery or a patient that has head and neck surgery, that they shouldn’t get postoperative radiation and they should go for an anti–PD-1. There’s no data that I’m aware of to guide that decision.

Transcript edited for clarity.