Microscopic Extranodal Extension in HPV-Negative Head and Neck Cancer and the Role of Adjuvant Chemoradiation

Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENE_mi) and role of adjuvant concurrent chemoradiation (CRT) for ENE_mi remain unclear. This study evaluates (1) the prognostic significance of ENE_mi in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients.

Retrospective cohort study.

Commission on Cancer (CoC)-accredited facilities.

This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENE_mi or no ENE who had undergone margin-negative surgery. The association of ENE_mi with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENE_mi receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS.

We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENE_mi. On multivariable analysis, ENE_mi was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENE_mi who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27).

For patients with HPV-negative HNSCC, pN+ with ENE_mi is associated with worse OS than pN+ without ENE. However, for patients with ENE_mi, concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENE_mi requires additional investigation.