Neoadjuvant PD-1 checkpoint blockade is associated with longer EFS/OS in resectable periauricular cSCC vs upfront surgery

In a retrospective, age- and stage-matched tertiary-center series of periauricular cutaneous squamous cell carcinoma (pCSCC) treated 2005–2025, neoadjuvant immunotherapy (checkpoint blockade; drug(s) not specified in the abstract) followed by curative-intent surgery (n=24) was compared with upfront surgery (n=61) in a cohort with similar baseline staging/disease burden and high recurrence at presentation (57% vs 54%). Neoadjuvant immunotherapy was associated with longer median event-free survival (EFS) (5.9 vs 3.4 years; HR 0.33, 95% CI 0.13–0.84; p=0.02) and higher 2-year EFS (87% vs 55%; p<0.05), and overall survival (OS) was longer (median not met vs 4.4 years; HR 0.32, 95% CI 0.11–0.90; p=0.031). While surgery + adjuvant RT remains the common standard approach for advanced/high-risk head/neck cSCC, prospective neoadjuvant anti–PD-1 studies (e.g., neoadjuvant cemiplimab in stage II–IV resectable cSCC) have shown high pathologic response rates (pCR ~51% and MPR ~64%), providing biologic plausibility for the survival signal seen here.