Limited benefit of surgical resection for oral cavity squamous cell carcinoma in patients with severe comorbidities

Purpose Primary surgery is standard for oral squamous cell carcinoma (OSCC) arising from oral cavity sites, but definitive radiation therapy may be considered for select patients. We evaluated whether surgical resection improved outcomes over definitive radiation therapy regardless of comorbidity. Methods Adults with invasive, clinically nonmetastatic stage I-IVB OSCC diagnosed from 2010 to 2017 were identified in the National Cancer Database. Primary surgery was defined as surgery to the primary site. Definitive radiation therapy was defined as no primary-site surgery and a total radiation dose of at least 6,600 cGy; this nonsurgical treatment group included patients treated with definitive radiation alone, definitive chemoradiation, or definitive radiation with non-chemotherapy systemic therapy. Overall survival was compared using multivariable Cox models and subgroup-specific propensity-score overlap-weighted Cox models by age group and Charlson-Deyo Comorbidity Classification (CDCC). Results The cohort included 49,791 patients; 46,778 underwent primary surgery and 3,013 received definitive radiation therapy. Definitive radiation therapy was associated with worse survival in multivariable analysis (HR, 1.395; 95% CI, 1.326–1.469; p < 0.001) and full-cohort overlap-weighted analysis (HR, 1.397; 95% CI, 1.326–1.471; p < 0.001). In CDCC-stratified analyses, the association favoring primary surgery remained significant for CDCC 0 and CDCC 1 but no longer statistically significant for CDCC 2 and CDCC ≥ 3. Formal interaction testing demonstrated variation by age and CDCC. Conclusion Definitive radiation therapy was associated with worse overall survival compared with primary surgery in OSCC. However, the survival disadvantage appeared attenuated among patients with higher comorbidity burden, supporting further evaluation of nonoperative strategies in selected patients with substantial comorbidity.