Applying High-Risk Criteria in CSCC Practice

The case-based discussion continues with an exploration of how high-risk features inform treatment decisions in clinical practice. The multidisciplinary panel discusses real-world application of C-POST eligibility criteria and the importance of comprehensive risk assessment when considering adjuvant therapy for cutaneous squamous cell carcinoma (CSCC).

This is Part 4 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 Barker: 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 if we're giving an immunotherapy 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 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: 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 with, 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 Patel: One of the cases that I think perspectives are important from all you guys, as a multidisciplinary approach, this particular patient, he had a small lesion, in his 60s. He presented with the right periocular lesion, was diagnosed as cutaneous SCC. He then underwent evaluation by his local dermatologist. So when somebody like that presents, let's say about a 2-cm lesion, in your practice, sun damaged, what are your thoughts usually as a first step? 

Dr Strasswimmer: So the de facto availability of cutaneous carcinoma staging that most dermatologists have, and that our thresholds are really, we have a 2-cm threshold that, within the Brigham and Women's staging criteria, bigger than 2 cm versus less than 2 cm matters. AJCC, that real threshold is 4 cm. Part of the question is, how do you measure the tumor size? So we have guidance that the traditional TNM staging should be done clinically based on the preoperative size. So if somebody comes with a 2-cm cutaneous squamous cell carcinoma sun damage, that's the bread and butter of what we do. 

Dr Patel: And so, after, again, discussions with our colleagues, we ultimately had a discussion with the patient as well. This was growing reasonably quickly, recurrent setting, sun-damaged skin. Clinically, and on imaging, it was going deep into the subcutaneous tissue and the parotid. And so again, all signs of being aggressive features, right? So we did offer him upfront surgery. And so we, in terms of the surgery that was performed, it was a wide local excision down to the parotid. I was very fortunate. Our pathology colleagues are excellent. They came back with the final pathology report on the main excision pretty rapidly. We took the patient back to re-excise the margin. The final pathology comes back after the re-excision, right? So, 2.9-cm primary lesion, the depth is 1.8 cm, going into the deep parotid tissue, invading the ear cartilage, the conchal cartilage in the front, moderate to poorly differentiated perineural invasions present, not the major nerves, but still microscopic perineural invasion. And then zero out of 21 lymph nodes from the neck were positive. So, thoughts on adjuvant radiation? 

Dr Barker: So despite complete margin assessment, this tumor recurred, and it recurred quite deeply. You're down into the parotid tissue is, 1.8 cm depth of invasion. That's deep. 

Dr Strasswimmer: Yeah. 

Dr Barker: There's perineural invasion. Probably because of how deeply this is invading, you're starting to see it involving the nerves as they get deeper. So this tumor is at risk for local recurrence as well as regional recurrence. Now, as part of your surgery, you assess the nodes. Pathologically, they appear negative. That's reassuring. But I'm concerned about another local recurrence in this location, certainly. And I think considering adjuvant therapy is warranted. 

Dr Wong: Yeah. So based on the pathologic features for this recurrent SCC, the patient would qualify for adjuvant cemiplimab. This is a case in which he had a recurrence in the field, and the recurrence was greater than 2 cm, so it was 2.9 cm. No lymph nodes involved, but there was perineural invasion. In addition, histologically, the tumor was poorly differentiated. So I think for many reasons, the patient would qualify. 

Dr Patel: So, for our next case, setting the stage, relatively young gentleman in his 40s, he's a trucker, but has a scalp cutaneous SCC. It was excised with negative margins initially, and he's got an underlying history of hematologic malignancies. So he's got CLL that's been ongoing, but very well controlled. And so now he presents about 6 months later with lumps in his neck. Not sure what it is. So we start initially with some imaging modalities. He gets a CT scan, which shows bilateral level 2 bordering to upper level 5 lymph nodes on both sides. Biopsies on both sides come back as cutaneous SCCs or at least SCC nonetheless. So no mucosal SCCs in the head and neck region. It's important to rule those out, so he doesn't have that. So, likely a regional metastases from his scalp that was treated with negative margins 6 months ago. 

Dr Barker: Yeah, this patient, I think, has probably developed these regional metastases as a result of his CLL. I think that immune-compromising condition increases the risk of regional metastasis, and it's generally a pretty rare event to happen, but patients in this scenario with this medical comorbidity, I think it's more common. I think the imaging workup here is really important, so you want to look carefully. I think bilateral biopsies were the right idea to ensure that you know what you're dealing with, and that's the squamous cell here. So now I think it's time for that multidisciplinary discussion about management. 

Dr Wong: Certainly, this patient would have qualified to participate in the C-POST study. So in the C-POST study, in which patients received adjuvant cemiplimab after surgery and postoperative radiation. Even patients who had CLL, as long as they were not requiring active treatment, were eligible to enroll. And I think that's an acknowledgement of the fact that patients with underlying hematologic malignancies, in particular CLL, are at particularly high risk for recurrence. I think that really speaks to the idea of making sure we're incorporating other patient factors into the discussion as to what constitutes high-risk CSCC. It's not just the findings at the time of the imaging or the findings at the time of pathologic assessment. It's all of the things, all of these factors, including patient factors. So, thinking about what other comorbid conditions the patient may have, is he fit enough to undergo a year of systemic therapy, even if the systemic therapy tends to be quite well tolerated? So I think it's a discussion. It's taking in not just the pathologic features or the tumor features, but also having a comprehensive assessment of the patient as well.