Neoadjuvant Immunotherapy for Periauricular Cutaneous Squamous Cell Carcinoma.

Abstract

The standard-of-care for advanced periauricular cutaneous squamous cell carcinoma (pCSCC) is surgery and adjuvant radiation therapy. Neoadjuvant immunotherapy recently demonstrated high pathologic response rates in patients with resectable pCSCC. This retrospective review was conducted at a tertiary cancer center and included patients with pathologically confirmed pCSCC within the periauricular area treated with curative-intent surgery with or without neoadjuvant immunotherapy from 2005 to 2025. Patients who received neoadjuvant immunotherapy followed by surgery were age- and stage-matched to those who underwent upfront surgery. The primary outcomes were event-free survival (EFS) and overall survival (OS), estimated using the Kaplan-Meier method. The study included 85 patients. Twenty-four (28.2%) of whom received neoadjuvant immunotherapy and 61 (71.7%) underwent upfront surgery. The two cohorts had no differences in staging or disease burden at presentation. Forty-eight patients presented with recurrent disease, equally distributed among the groups (57% vs. 54%, p > 0.05). Patients receiving neoadjuvant immunotherapy had longer median EFS than those undergoing upfront surgery (5.9 vs. 3.4 years; hazard ratio [HR], 0.33; 95% confidence interval [CI], 0.13-0.84; p = 0.02). Specifically, EFS at 2 years was 87% in the neoadjuvant group compared with 55% in the upfront surgery group (p < 0.05). Median OS was also longer in the neoadjuvant group (not met vs. 4.4 years; HR, 0.32; 95% CI, 0.11-0.90; p = 0.031). Neoadjuvant immunotherapy improved survival outcomes in patients with advanced resectable pCSCC. These findings underscore the importance of including this patient population in upcoming randomized trials.