Aims: Immunotherapy is the standard of care for advanced cutaneous squamous cell carcinoma (CSCC) resulting in durable responses1,2. CSCC has a propensity for perineural spread (PNS) which is associated with poorer treatment outcomes3. PNS is not captured by traditional response assessment criteria used in clinical trials, such as RECIST 1.1, and there is limited literature documenting radiographic PNS responses to immunotherapy. In this study we assess PNS responses to immunotherapy using a new grading system.
Methods: This is an Australian single-center retrospective review of patients with advanced CSCC who were treated with immunotherapy between April 2018 and February 2022 who had evidence of PNS on MRI post multidisciplinary review. The primary outcome was overall blinded radiological response in PNS (using graded radiographic criteria) post commencement of immunotherapy at three defined timepoints (<5 months, 5-10 months, >10 months). A secondary outcome included a correlation between RECIST1.1 and PNS assessments.
Results: 20 patients were identified (cemiplimab 17, pembrolizumab 3). Median age was 75.7 years and 75% (n=15) were male. All patients had locoregionally advanced disease and no distant metastases. Median follow-up was 18.5 months. 75% (n=15) demonstrated a PNS response by 5 months. Three patients experienced pseudoprogression in both their PNS and RECIST1.1 measurable disease. Two patients had PNS progression by the end of study follow up. RECIST1.1 and PNS responses were largely concordant (Cohen’s Kappa 0.62). Two pseudoprogressive cases ultimately demonstrated improvement in PNS with immunotherapy, whilst the third had a near complete pathological response at surgery.
Conclusions: PNS response to immunotherapy can be documented on MRI using graded radiographic criteria. High response rates were seen in PNS with the use of immunotherapy in this cohort and these responses were largely concordant with RECIST1.1 assessments.