Neoadjuvant Cemiplimab for Resectable Locoregionally Advanced Cutaneous Squamous Cell Carcinoma: A Case Series

INTRODUCTION: A Phase II trial demonstrated that neoadjuvant cemiplimab was associated with pathologic complete response (pCR) in 51% of patients with locoregionally advanced cutaneous squamous cell carcinoma (cuSCC). We evaluated real-world radiographic and pathologic responses to neoadjuvant cemiplimab and assessed radiologic-pathologic concordance. METHODS: Retrospective single-institution cohort study including 18 patients with locoregionally advanced head and neck cuSCC treated with neoadjuvant cemiplimab before curative-intent surgery between 2019 and 2024. Pathologic and radiographic responses were assessed using pathology review and RECIST 1.1/iRECIST. RESULTS: pCR occurred in 11 patients (61%) and major pathologic response (MPR) in 2 (11%), yielding a 72% combined pathologic response rate. Among 16 patients with evaluable imaging, only 33% demonstrated radiographic partial response (PR), and none achieved radiographic complete response. Radiologic response frequently underestimated tumor clearance. CONCLUSIONS: Neoadjuvant cemiplimab produced high pathologic response rates in real-world practice, while RECIST-based imaging underestimated true tumor response, highlighting limitations of anatomic imaging in immunotherapy-treated cuSCC.