Survival benefit of post-operative chemotherapy for intermediate-risk advanced stage head and neck cancer differs with patient age

Objectives: The National Comprehensive Cancer Network (NCCN) guidelines state that surgical patients with advanced-stage head and neck cancer (HNC) and risk factors other than extranodal extension (ENE) or positive margins should consider post-operative chemoradiation (POCRT). The goal of our study was to determine if POCRT is associated with overall survival (OS) compared with post-operative radiation therapy (PORT) and whether this varies with patient age. Material and Methods: We conducted a retrospective study of 5319 adult patients with stage III-IV HNC who received primary surgical treatment with POCRT or PORT in the National Cancer Database (2010–2013). Patients with distant metastases, ENE, and positive margins were excluded. Intermediate risk features included pT3-T4, pN2-N3 disease, and lymphovascular invasion. Our main outcome was overall survival (OS). Statistical analysis included chi-squared tests and Cox proportional hazards regressions. Results: On multivariable analysis for non-oropharyngeal cancer patients <70 years, POCRT was associated with improved OS for T1-4N2-3 disease (hazard ratio [HR], 0.73, 95% confidence interval [CI]; 0.58–0.93) but was not associated with OS for T3-4N0-1 disease (HR, 0.92; 95% CI, 0.71–1.19). For patients ≥70 years, POCRT was not associated with improved OS for patients with T1-4N2-3 disease (HR, 1.21; 95% CI, 0.79–1.86) or T3-4N0-1 disease (HR, 1.08; 95% CI, 0.71–1.65). For oropharyngeal cancer patients with HPV-positive disease, POCRT was associated with decreased OS (HR, 9.52; 95% CI, 2.38–38.08). Conclusion: Chemoradiation may offer a survival benefit for non-oropharyngeal intermediate-risk advanced-stage HNC patients <70 years of age with T1-4N2-3 disease, but may not benefit those ≥70 years of age or those with T3-4N0-1 disease.