Survival Benefit of Postoperative Chemotherapy for Intermediate-Risk Advanced Stage Head and Neck Cancer

Abstract

The National Comprehensive Cancer Network guidelines state that surgical patients with advanced stage head and neck cancer with risk features other than extracapsular extension (ECE) or positive margins should consider postoperative chemoradiation (CRT). No clinical trial has adequately assessed the survival benefit of adding adjuvant chemotherapy to this subgroup of intermediate risk patients. Adult patients with stage III and IV head and neck squamous cell carcinoma (HNSCC) who received primary surgical treatment with postoperative CRT or RT from 2010 to 2014 were extracted from the National Cancer Database. Patients with pT1-2N1 disease, distant metastases, ECE, and positive margins were excluded. Our main outcome was overall survival (OS). Statistical analysis included χ2 tests and Cox proportional hazards regression analysis. We identified 5552 adult patients with intermediate-risk advanced stage HNSCC. Compared to those who received postoperative RT, those who received CRT were more likely to be <70 years of age (86.7% vs 77.6%, P < .001), have a Charlson/Deyo comorbidity score of zero (78.5% vs 74.8%, P = .003), have pN2-3 disease (70.1% vs 45.1%, P < .001), and have private insurance (48.0% vs 41.3%, P < .001). Patients at community programs were more likely to receive CRT than those at academic centers (47.5% vs 37.3%, P < .001). On multivariable analysis for patients <70 years of age, CRT was associated with improved OS for patients with T1-4N2-3 disease (hazard ratio [HR], 0.73; 95% confidence interval [CI] 0.58-0.93) but was not associated with survival for patients with T3-4N0-1 disease (HR, 0.92; 95% CI 0.71-1.19). For patients ≥70 years of age, CRT 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 human papilloma virus positive disease, CRT was associated with decreased OS (HR, 6.74; 95% CI 2.08-21.87). Chemoradiation may offer a survival benefit for non-HPV intermediate-risk advanced stage HNSCC 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. Postoperative CRT is more commonly offered than RT in the community than in academic centers for these patients. Further research is needed to improve risk stratification of patients with intermediate risk features and determine who may benefit from CRT.