The Role of Radiotherapy to the Primary Site in Oropharyngeal Cancer with Limited Metastases—An Analysis of a Hospital-Based Registry

Background/Objectives: Limited metastatic squamous cell carcinoma of the oropharynx (OPC) lacks clear management guidelines, especially for HPV-associated disease. The objective of this study was to investigate if primary site radiotherapy (RT) benefits overall survival in limited metastatic OPC. Methods: Utilizing the National Cancer Database (NCDB), patients aged 18–90 with OPC presenting as cM1 with limited metastatic disease to one distant site were identified. Propensity score matching, Cox-proportional hazards models, and Kaplan–Meier estimates were employed to assess factors associated with overall survival. Results: In this study, 1056 patients were included with metastases involving bone (19.0%), brain (0.8%), lung (52.9%), liver (10.1%), and lymph nodes (20.4%). Treatment modalities included 54.6% receiving primary site RT, 45.4% receiving no RT, and 69.9% undergoing systemic therapy. For HPV-positive patients, RT (HR 0.64, p = 0.0026) and receipt of chemotherapy (HR = 0.57, p = 0.0057) were associated with improved overall survival, while bone and lung metastases were associated with decreased survival (HR = 1.75 and 1.39, p = 0.0041 and 0.041, respectively). In HPV-negative cases, survival also correlated with RT (HR = 0.65, p = 0.0047), receipt of chemotherapy (HR = 0.45, p < 0.001), clinical T4 disease (HR = 1.99, p = 0.012), presence of bone metastases (HR = 2.52, p < 0.001), lung metastases (HR = 1.49, p = 0.035), and lymphovascular invasion (HR = 1.10, p < 0.001). Overall, patients who received RT showed increased median overall survival from 9.9 to 16.1 months (p < 0.001) compared to those who did not. When stratified by RT and HPV status, there was higher median survival for both HPV-positive (from 17.1 to 24.9 months, p < 0.001) and HPV-negative patients (from 8.4 to 12.9 months, p = 0.0016) who received RT compared to those who did not. Conclusions: Primary-site radiotherapy may positively impact overall survival in limited metastatic OPC, irrespective of HPV status.