Patterns of care and comparative effectiveness of intensified adjuvant therapy for resected oropharyngeal squamous cell carcinoma in the human papillomavirus era

Importance: There is a growing debate on the relative benefits of adjuvant chemoradiotherapy (CRT) and boost doses of postoperative radiotherapy (B-PORT) in oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery, especially for patients with human papillomavirus (HPV)-driven disease. Objective: To characterize the recent patterns of care in and overall survival (OS) outcomes following the use of adjuvant CRT and B-PORT after primary surgery for OPSCC. Design, Setting, and Participants: Retrospective analysis of patients in the National Cancer Database with stage III to IVA-B OPSCC treated with surgery and adjuvant radiotherapy between 2010 and 2012 at Commission on Cancer-accredited facilities. The data analysis was performed between June 15, 2015, and May 4, 2016. Main Outcomes and Measures: The primary outcomes were prevalence of CRT and B-PORT, and OS. The primary predictors were HPV positivity and high-risk pathologic features (HRPFs) (extracapsular extension and positive surgical margins). Results: Of the 1409 patients (1153 [82%] male; median age, 57 [interquartile range {IQR}, 51-63] years), 873 (62%) and 789 (56%) patients received CRT and B-PORT, respectively; most patients (n = 583 [79%]) with HRPFs received CRT, and many patients (n = 227 [40%]) without HRPFs received CRT. Multivariable predictors of CRT included adverse pathologic features (extracapsular extension [OR, 6.99; 95%CI, 5.22-9.35], positive surgical margins [OR, 2.07; 95%CI, 1.50-2.87],≥6 involved nodes [OR, 2.34; 95%CI, 1.39-3.92], or low-neck disease [OR, 1.52; 95%CI, 1.01-2.28]), and treatment at a nonacademic institution (OR, 1.59 [95%CI, 1.21-2.10] for comprehensive community cancer center vs academic program). Patients with HPV-positive disease (OR, 0.47; 95%CI, 0.33-0.68) were less likely to receive CRT; this decrease was limited to absent HRPF treated at academic institutions (n = 173, 44 [25%] received CRT). With a median follow-up of surviving patients of 27 (IQR, 21-33) months, the 2-year OS probability was 92%(95%CI, 90%-94%). Multivariable analysis including age, sex, pathologic T stage, 6 or more positive nodes, and educational status confirmed the prognostic impact of HPV positivity (hazard ratio [HR], 0.41; 95%CI, 0.21-0.80) and HRPFs (positive surgical margins [HR, 2.15; 95%CI, 1.27-3.66] and ≥ 6 involved nodes [HR, 2.11; 95%CI, 1.13-3.93]), but neither CRT (HR, 1.27; 95%CI, 0.70-2.30) nor B-PORT (HR, 1.04; 95%CI, 0.63-1.73) was associated with improved OS. Conclusions and Relevance: Postoperative CRT and B-PORT following resection of OPSCC were dependent on factors beyond HRPFs, including HPV status and treatment at an academic institution. No benefit was seen with intensified adjuvant therapy, supporting enrollment of the HPV-positive population into deintensification trials.