When would you offer neoadjuvant immunotherapy prior to Mohs surgery in a locally advanced squamous cell carcinoma for which clearance may require enucleation?

I would flip this question around and answer that radiotherapy is often a terrific option around the eyes, and it should always be considered in this area, especially when a radical surgical procedure is being entertained.

Between en face therapy with a shield (superficial, electrons) and IMRT/VMAT, we can usually develop an oncologically sound, organ-preserving treatment approach.

The potential loss of an eye involves major decision-making and pre-planning with a team. I remember as a fellow working with @Dr. First Last at The Eye Foundation Hospital Foundation in Birmingham, hospital bylaws required the surgeon to wake a patient and get permission if a Mohs case got to the point of requiring exenteration. The answer to this question always involves the plural tense. Our Mohs fellows always present such cases to our local tumor board or to one of three or four tertiary institutions near us, sometimes virtually. In the case of an SCC, which is pushing on the globe or goes behind the equator, defined by the extraocular muscles, confirmation by proper imaging and consideration of radiation or PD1 can be discussed by the...

Since the question is about immunotherapy, my answer is yes. I would start on cemiplimab neoadjuvant for at least 2 cycles, but I prefer 4 cycles prior to surgery to deepen the response. Many patients will not need surgery afterwards, as the cemiplimab can cure a significant percentage of these patients. A couple of phase 2 studies showed about 60-70% response rate (RECIST or pathological) in untreated SCC patients. If immunotherapy fails, I agree with radiotherapy in the neoadjuvant setting. If one can prevent organ dysfunction (enucleation, facial paralysis, disfiguration, etc...) one should deploy every effort to do so.

• Salzmann et al., PMID 32882466 and
• Ferrarotto et al., PMID 34187851