Recognizing High-Risk CSCC

In this video, the multidisciplinary panel reviews the clinical, pathologic, and patient-related features that define high-risk cutaneous squamous cell carcinoma (CSCC), including tumor characteristics, nodal involvement, perineural invasion, and immunocompromised status. The panel also examines staging systems, high-risk criteria used in the C-POST trial, and the role of the multidisciplinary team in assessing recurrence risk.

This is Part 1 of 5:

• Part 1: Recognizing High-Risk CSCC
• Part 2: Integrating Adjuvant Therapy in High-Risk CSCC
• Part 3: Multidisciplinary Coordination in High-Risk CSCC
• Part 4: Applying High-Risk Criteria in CSCC Practice
• Part 5: Safety Monitoring in High-Risk CSCC

Dr Strasswimmer: Two categories. First is the specific tumor, and we're going to talk about some in detail, the size, whether it's recurrent, poorly differentiated. But the other part is actually the patient. So in other words, a 94-year-old person who comes in who might have cardiac issues, their ability to go through salvage therapy or another alternate therapy might be a little bit difficult than, say, somebody who's a bit younger and a bit healthier. So it's both high risk from a patient perspective and then high risk from the tumor specifics as well. 

Dr Wong: From a very practical perspective as a medical oncologist, high risk often means it's a patient showing up in my clinic, to put it very basically, because most patients with cutaneous malignancies first start with their friendly dermatologist. And then if it's something that's higher, more advanced or more complicated, more complex that requires more than Mohs surgery, then Dr Patel, you oftentimes get involved. And then that's where I tend to hear about patients through our multidisciplinary discussions and tumor boards. 

Dr Strasswimmer: I think you're exactly right. And I guess, with that in mind, high risk is as a dermatologist and Mohs surgeon, when I need to pick up the phone to call one of my colleagues and say, "By the way, I'm going to be sending you somebody to see you." 

Dr Wong: Right. 

Dr Barker: Cancer specialists, medical oncologists, surgical oncologists, radiation oncologists, I think are accustomed to using the AJCC staging systems for the myriad of cancers that we take care of. And for that reason, I think in the context of cutaneous squamous cell carcinoma, more often go to that as the staging system. And the UICC 8 system, which is very similar to the AJCC, is probably used more internationally as well. I think the dermatology community, the Mohs community, has embraced the Brigham and Women's System, which certainly has its merits. But I do think that I see the adoption of the different staging systems varying across specialists that see these patients. 

Dr Wong: From a medical oncology perspective, I am used to using TNM staging, which aligns mostly with AJCC criteria. But certainly we know that the clinical features that are incorporated with these other staging systems are particularly relevant for cutaneous squamous. 

Dr Strasswimmer: I think it's where maybe the historical perspectives of our field come from because in dermatology and Mohs surgery, we don't really stage solid tumors historically because the tumors we deal with are measured differently. We measure them clinically rather than radiology. And so I think the Brigham and Women’s came out also because we see these in-between ones, or those ones that have us in clinic a little more worried, and helps to break down those subgroups that we have there. 

Dr Wong: Mm-hmm. 

Dr Patel: Yeah, we call it the H zone, right, the upper lip and then almost looks like an H across the face and that's, in front of the ears, across the lip. Those are the high-risk areas anatomically as well. The other thing that I like about the guidelines are they are frequently updated. I think expert opinions, people meet, they're updated at least two to three times a year. I think those are advantages for practicing physicians. 

Dr Barker: I could also say that for folks that perhaps don't see cutaneous squamous cell carcinoma all the time, these criteria, I think they help develop a clinical gestalt about risk. We perhaps don't use a laundry list to go through and itemize each of these features for every patient. But I think when familiarizing yourself with this entity, patients that are at higher risk for recurrence, these criteria can be useful to develop that clinical gestalt about the natural history of what's to come. 

Dr Patel: For me, actually taking a step back, the conversation starts right when I see the patient and engaging radiation oncologists and medical oncologists at our tumor boards, and working as a team in identifying the patients much earlier who are potentially at high risk, and then adjusting the treatment plan. And in fact, sometimes I'll have the patients meet with our radiation medical oncologist even before I operate so that the expectations are set. 

Dr Barker: Yeah. I think the criteria that were put forth for, for example, the C-POST clinical trial, I think really encapsulate those patients that are at highest risk of developing recurrence. I consider these very important features. Upon recognition of these, this sets off alarm bells that we ought to be thinking about what can be done to help this patient because of the anticipated high risk of recurrence. So it's very important. Of all patients with non-distant metastatic cutaneous squamous cell carcinoma, these are what we think are the features that are most significant for predicting recurrence despite surgery and radiation. And that needs to be well recognized and known by physicians that are taking care of these patients. 

Dr Patel: We should mention that the high risk criteria from the C-POST are the nodal disease, the extranodal extension, the in-transit metastases, the perineural invasion, the aggressive, the T4 lesions, and then the recurrent cutaneous CSCCs. 

Dr Barker: You really need to confirm these very high-risk criteria are present when considering this. And I think that getting the community to really come to a strong understanding of what really were those criteria that made a patient eligible for the C-POST trial is so important because, frankly, I think there's a risk. If we're giving an immune therapy for a patient who is in fact not very high risk for recurrence, that risk-benefit ratio can change quite dramatically. So I think these criteria you've mentioned for participation in the C-POST trial, those criteria that make a patient really high risk for recurrence, I think it's important that our community has a firm grasp on those. 

Dr Wong: Another one that gets a little tricky and you really have to dive deep into the details is what is recurrent CSCC? And so in the C-POST study for eligibility, it was very specific. Patients not just had to recur within the resection area, but they also had to have certain additional features. High nodal stage, for example, the recurrent lesion had to be more than 2 cm in size. The lesion had to be greater than or equal to T3 stage, or histologically the tumor had poor differentiation. So I think it's important to, as you said, really make sure that we're treating patients and recommending these therapies in patients who are appropriate. 

Dr Strasswimmer: Within the world of dermatology, sometimes dermatologists get confused about what's recurrence versus not recurrence. We have a phenomenon called eruptive keratoacanthomas whereby a little more-or-less benign squamous cell carcinoma may occur within a surgical wound. So it's important for us to talk to our dermatology colleagues about what is a recurrent SCC as defined by the C-POST study for which patients might benefit from immunotherapy versus something else that's not necessarily recurrent with the capital R. 

Dr Barker: And the specialists who aren't at the table today and their role in this process of risk assessment, our pathology colleagues,… 

Dr Strasswimmer: That's right. 

Dr Barker: ...our radiology colleagues, these folks who when they have a strong grasp of these subtle histopathologic findings, these subtle radiographic findings that really start to set off our alarm bells about this patient has spread along one of the cranial nerves, you can see it on the MRI, it's subtle, but it's there. These folks, they play a really important role in this risk assessment process. So we shouldn't forget about them and their inclusion in these patients' care and evaluation. 

Dr Patel: And that's often the case in our multidisciplinary tumor board discussions where we have a radiologist and these are specific features that I ask, "Is there a tracking along the facial nerve or the auriculotemporal nerve or the trigeminal nerve that's making this a high-risk feature as a named nerve?" Or our pathologist in a postoperative setting, we're looking at the extranodal extension, and what's the amount of extranodal extension? And so you're right. I think as a community, all of us are treating, but yes, radiologists and pathologists need to be acknowledged. 

Dr Wong: Right. And I think the other, you brought up patient factors beyond comorbidities. One comorbidity I think about a lot as a medical oncologist would be things like underlying or concurrent hematologic malignancies like CLL, chronic lymphocytic leukemia, as well as patients who are immunocompromised in other ways, solid organ transplant patients and things like that. And while they're a relatively small patient population, we know that those patients in particular have exceedingly high-risk disease and a treatment-refractory disease.