Immune Checkpoint Inhibition in Locally Advanced Periocular Squamous Cell Carcinoma (POLA-SCC)

To review the existing literature on the use of immune checkpoint inhibitors in the management of locally advanced periocular squamous cell carcinoma (POLA-SCC) and to contextualize current evidence through a representative clinical case.

A narrative review of published studies evaluating programmed cell death protein-1 (PD-1) inhibition for advanced periocular cutaneous squamous cell carcinoma was performed. In addition, a detailed case of recurrent upper eyelid squamous cell carcinoma treated with multiple surgical excisions followed by PD-1 inhibitor therapy is presented to illustrate real-world clinical challenges and outcomes.

A 75-year-old man with upper eyelid SCC experienced rapid local recurrence despite repeated margin-controlled excisions and complex reconstructive procedures, resulting in significant eyelid dysfunction, ocular surface disease, and visual decline. Subsequent treatment with the PD-1 inhibitor cemiplimab achieved meaningful tumor control and disease stabilization. Review of the current literature demonstrates consistently high response rates to PD-1 inhibition in locally advanced periocular SCC, even in the presence of tumors with perineural invasion and orbital involvement, frequently allowing avoidance of mutilating surgical procedures such as orbital exenteration. Immune checkpoint inhibitors were generally well tolerated, with ocular adverse events being uncommon and typically manageable.

Accumulating evidence supports immune checkpoint inhibition as an effective, eye-sparing, and vision-sparing therapeutic strategy for locally advanced periocular squamous cell carcinoma. Integration of PD-1 inhibitors into multidisciplinary management paradigms may reduce surgical morbidity, preserve ocular function, and shift treatment toward more conservative approaches in appropriately selected patients.