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

Abstract

Objective

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.

Study Design

Retrospective cohort study.

Setting

Commission on Cancer (CoC)–accredited facilities.

Methods

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.

Results

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).

Conclusion

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.