Upfront Surgery Versus Definitive Radiotherapy: Competing Risk Analyses in Early Stage Oropharyngeal Cancer

Abstract Objective To compare the survival outcomes of early‐stage oropharyngeal cancer (OPC) patients treated with upfront surgery versus definitive radiotherapy (RT). Study Design Retrospective observational study. Setting Publicly available database. Methods A total of 1877 patients with T1‐2N0‐1M0 OPC were retrieved from the Surveillance, Epidemiology, and End Results database. Primary endpoints were cancer‐specific and noncancer mortalities, which were estimated using cumulative incidence function and compared by Gray's test. Univariate and multivariate Fine‐Gray subdistribution hazard models were used to estimate the effects of treatment modality on mortality. Subgroup analyses were performed in propensity‐score‐matched cohorts. All the analyses were conducted separately in human papillomavirus (HPV)‐negative and HPV‐positive cohorts. Results In the HPV‐negative cohort, definitive RT was independently associated with increased risk of cancer‐specific mortality (adjusted subdistribution hazard ratio [SHR], 2.29; 95% confidence interval [CI], 1.42‐3.68; p = .001) and noncancer mortality (adjusted SHR, 2.74; 95% CI, 1.50‐5.02; p = .001). In the HPV‐positive cohort, definitive RT and upfront surgery could achieve similar cancer‐specific and noncancer survival outcomes. Conclusion Upfront surgery is associated with lower cancer‐specific and noncancer mortality in HPV‐negative early‐stage OPC patients. However, in the setting of HPV‐positive early‐stage OPC with better prognosis, the 2 treatment modalities have similar efficacy in terms of cancer‐specific and noncancer survival outcomes. In the future, carefully designed prospective clinical trials are needed to confirm our findings.