Radiation Therapy and Overall Survival in Perineural Invasion-Positive Cutaneous Squamous Cell Carcinoma of the Head...

The role of radiation therapy (RT) in improving survival outcomes for patients with high-risk cutaneous squamous cell carcinoma (cSCC) and perineural invasion (PNI) remains incompletely defined. We evaluated overall survival (OS) in surgically treated patients with head and neck cSCC with or without PNI, stratified by receipt of RT.

This retrospective cohort study queried the National Cancer Database (NCDB) for adults with head and neck cSCC diagnosed between 2018 and 2021, identified by cutaneous head-and-neck primary-site codes (C44.0-C44.4) together with squamous-cell histology coding (ICD-O-3 8050-8084). Only patients who underwent definitive surgery were included; biopsy-only patients were excluded. Patients with missing data on race/ethnicity, age, sex, or PNI status were excluded. OS was evaluated using Kaplan-Meier curves and compared with the log-rank test. Multivariable Cox proportional-hazards regression, adjusted for the available demographic covariates, assessed associations between clinicopathologic variables and OS, with an interaction term used to test whether the association of RT with OS differed by PNI status. Results are reported as hazard ratios (HRs) with 95% confidence intervals (CIs). Statistical significance was defined as p < 0.05.

Among 929 patients included in the final analysis (276 PNI-positive, 653 PNI-negative), PNI-positive patients were more likely to be White (92.0% vs. 85.8%, p = 0.018) and to have received RT (49.6% vs. 11.3%, p < 0.001). OS did not differ significantly between PNI-positive and PNI-negative patients on univariate or multivariable analysis (log-rank p = 0.120; adjusted HR = 1.38, 95% CI: 0.98-1.96, p = 0.066). A statistically significant PNI-RT interaction was identified on both univariate (HR = 0.60, 95% CI: 0.34-1.06, p = 0.042) and multivariable analysis (HR = 0.65, 95% CI: 0.37-1.15, p = 0.016), indicating that the apparent survival association of RT was concentrated among PNI-positive patients.

In this NCDB cohort, PNI-positive patients who did not receive RT had worse survival than PNI-negative patients not receiving RT, whereas PNI-positive patients who received RT had outcomes comparable to the PNI-negative reference group. These hypothesis-generating findings are consistent with the possibility that RT may attenuate the adverse prognostic association of PNI in head and neck cSCC; however, the analysis is susceptible to confounding by indication and to the limitations of administrative data, and prospective studies are warranted to validate these results.