Response of Perineurial Tumor Spread from Cutaneous Squamous Cell Carcinoma Treated with Immunotherapy

Anti-programmed-death-1 receptor immune check point inhibitor (anti PD-1 ICI) therapy has shown benefit in advanced cSCC, however imaging response of PNS to immunotherapy remain incompletely characterized. This retrospective study included 9 patients with imaging surveillance of cSCC PNS treated with anti-PD-1 therapy, and narrative literature review of cSCC-associated PNS treated with immunotherapy. Baseline and follow-up imaging were evaluated for PNS zone, cranial nerve involvement, and treatment response. Zone 1 (extracranial) involvement was present in 2 patients, Zone 2 (skull base/foraminal) in 0 patients, and Zone 3 (intracranial) in 7 patients. Best imaging outcome was complete response (CR) = 3 patients, partial response (PR) = 5 patients, and stable disease (SD) = 1 patient. No patients had PNS progressive disease (PD) on surveillance imaging; median follow-up was 37 months. One patient had pseudoprogression (PsP), with early MRI worsening and subsequent improvement. Narrative literature review identified 101 patients, with CR = 35%, PR = 43%, SD = 9%, PD = 10%, clinical response in 1%, unknown 2%, and PsP = 1%. Anti-PD-1 immunotherapy may provide durable imaging control of cSCC-associated PNTS, with objective response visible on MRI. Early post-treatment MRI worsening should be interpreted cautiously as pseudoprogression and imaging response lag may occur. Changes in cranial nerve enhancement and enlargement can serve as a surrogate marker for overall response, which could broaden inclusion of PNS as a measure for clinical trials.