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- Presentation
Advances in Immunotherapy for Advanced Cutaneous Squamous Cell Carcinoma
Description
The speaker, a Mohs surgeon and cutaneous oncologist, reviewed advances in immunotherapy for advanced cutaneous squamous cell carcinoma (CSCC), emphasizing that dermatologists should think beyond surgery and recognize when patients may benefit from systemic treatment. He explained that advanced CSCC includes locally advanced, regional, and metastatic disease, and that outcomes are poor once spread occurs. The talk covered PD-1 and PD-L1 inhibitors, EGFR inhibitors, and chemotherapy, with a focus on clinical trial data for neoadjuvant and adjuvant use. Semiplimab showed strong activity in resectable and locally advanced disease, with about 50% complete pathologic responses in neoadjuvant studies and a 68% reduction in recurrence in the C-POST adjuvant trial. Pembrolizumab did not show benefit in Keynote 630, while cosibelumab, a PD-L1 blocker, showed similar efficacy with potentially fewer toxicities, making it attractive for some higher-risk patients such as transplant recipients or those with autoimmune disease. The speaker reviewed immune-related adverse effects, contraindications, and the importance of performance status, noting that age alone is not a contraindication. He also discussed circulating tumor DNA for surveillance, intralesional therapies, and the idea that immunotherapy may increasingly be used before surgery to shrink tumors and improve outcomes, especially in underrecognized high-risk stage I disease.
View moreConclusions
- For advanced cutaneous squamous cell carcinoma, immunotherapy is increasingly a central treatment option rather than something reserved only after surgery and radiation fail.
- Neoadjuvant cemiplimab can produce substantial pathologic responses in resectable stage II to IV cSCC and may improve surgical outcomes.
- Adjuvant cemiplimab after surgery and radiation reduces recurrence and disease-free survival events in high-risk cSCC, though it carries a higher rate of serious adverse events than placebo.
- Pembrolizumab did not show a clear adjuvant benefit in KEYNOTE-630, so its use in this setting should be viewed cautiously.
- Cosibelimab appears to have efficacy similar to other checkpoint inhibitors and may have a somewhat favorable toxicity profile, making it potentially useful for patients at higher risk of immune-related toxicity.
- Checkpoint inhibitors can cause immune-related adverse events in any organ system, so careful toxicity monitoring and patient counseling are essential.
- Chemotherapy and EGFR-targeted therapy remain fallback options when PD-1 or PD-L1 therapy fails or cannot be used, but they are generally less favored.
- Patient selection for immunotherapy should rely on functional status, comorbidities, and multidisciplinary judgment rather than age alone.
- Circulating tumor DNA is a promising tool for detecting disease burden, monitoring response, and identifying recurrence, but its sensitivity in cSCC is still imperfect.
- Intralesional approaches, especially intralesional interleukin-2, show encouraging response rates and may offer a surgery-sparing option for selected patients.
- Traditional staging alone misses some high-risk T1 tumors, so additional risk factors such as head and neck location, differentiation, depth, fat invasion, and small-caliber PNI should influence management.
- Gene expression profiling may help identify patients whose biologic risk is higher than their anatomic stage suggests and could guide escalation to immunotherapy or radiation.
- Overall, the field is moving toward earlier, more personalized, and less purely surgery-centered treatment strategies for cSCC.
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