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Nonmelanoma Skin Cancer Studies / Head and Neck Cancer Studies · Journal article
Head & Neck · August 8, 2026
Encouraging direction, but not yet definitive.
In this NCDB cohort of surgically treated head and neck cSCC, PNI-positive patients receiving RT had OS comparable to PNI-negative patients, whereas untreated PNI-positive patients had worse survival. The finding is consistent with a protective effect of RT in PNI-positive disease but is subject to confounding by indication and requires prospective validation.
Retrospective cohort study. Adults with surgically treated head and neck cSCC diagnosed 2018–2021, with complete demographic and PNI status data. Intervention: Radiation therapy (receipt yes/no). Compared with: No radiation therapy, stratified by PNI status. n = 929. National Cancer Database (US).
Among 929 patients (276 PNI-positive, 653 PNI-negative), PNI-positive patients were more likely to receive RT (49.6% vs. 11.3%, p < 0.001) On univariate analysis, PNI–RT interaction was statistically significant (HR = 0.60, 95% CI: 0.34–1.06, p = 0.042) On multivariable analysis, PNI–RT interaction remained significant (HR = 0.65, 95% CI: 0.37–1.15, p = 0.016)
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The finding that RT may attenuate the adverse prognostic effect of PNI in head and neck cSCC is hypothesis-generating and potentially clinically relevant, but the retrospective, observational nature and susceptibility to confounding by indication preclude definitive clinical recommendations. Prospective studies are needed before changing treatment practice.
Retrospective cohort study from a large national registry with clear methodology and a clinically relevant finding (RT may improve OS in PNI-positive cSCC), but susceptible to confounding by indication and limited by observational design; prospective validation is needed.
As stated by the source record.
Quoted from the source exactly as published.
The finding that RT may attenuate the adverse prognostic effect of PNI in head and neck cSCC is hypothesis-generating and potentially clinically relevant, but the retrospective, observational nature and susceptibility to confounding by indication preclude definitive clinical recommendations. Prospective studies are needed before changing treatment practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
ABSTRACT Background 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. Methods 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. Results 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. Conclusions 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.
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