Survival and Patterns of Relapse of Cutaneous Squamous Cell Carcinoma With Large Nerve Perineural Spread After Skull Base Surgery and/or Radiation Therapy.

Purpose: The aim of our study was to evaluate survival and patterns of relapse for patients with perineural spread (PNS) of cutaneous squamous cell carcinoma (cSCC), who have undergone curative intent skull base surgery and/or radiation therapy. In addition, we modified the classification of zone 2 disease into 2a and 2b and reported the respective outcome.

Methods and materials: A review of a prospective database of patients who received diagnoses of PNS of cSCC and were treated with curative intent skull base surgery and/or radiation therapy between the years of 2013 and 2020 was conducted. Kaplan-Meier methods were used to estimate relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS). Cox proportional hazard modeling was performed to test associations between patient factors and survival outcomes.

Results: Eighty patients with a median follow-up of 36 months were included in the study. The 5-year RFS was 61% (95% CI, 48%-71%), the DSS was 77% (95% CI, 63%-86%), and OS was 67% (95% CI, 53%-78%). In multivariable modeling, involvement of 2 or more nerves was strongly associated with worse 5-year RFS (HR, 4.0; P ≤ .001), DSS (HR, 4.5; P = .004), and OS (HR, 4.3; P = .002). Age group (≥65 years) (HR, 5.1; P = .010) and immune compromise (HR, 10.7; P = .001) were strongly associated with worse OS but not DSS or RFS. The majority of relapses (60%) occurred at the local skin sites.

Conclusions: Our study demonstrated surgery followed by radiation therapy was safe and effective in the management of cSCC with PNS. We did not detect a difference in outcome between zones 2a and 2b though further study is required. The most common mode of relapse was at the skin epidermis and/or adjacent dermis highlighting the importance of adequate local skin dose delivery.