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

<b>Background/Objectives:</b> 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. <b>Methods:</b> 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. <b>Results:</b> 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, <i>p</i> = 0.0026) and receipt of chemotherapy (HR = 0.57, <i>p</i> = 0.0057) were associated with improved overall survival, while bone and lung metastases were associated with decreased survival (HR = 1.75 and 1.39, <i>p</i> = 0.0041 and 0.041, respectively). In HPV-negative cases, survival also correlated with RT (HR = 0.65, <i>p</i> = 0.0047), receipt of chemotherapy (HR = 0.45, <i>p</i> < 0.001), clinical T4 disease (HR = 1.99, <i>p</i> = 0.012), presence of bone metastases (HR = 2.52, <i>p</i> < 0.001), lung metastases (HR = 1.49, <i>p</i> = 0.035), and lymphovascular invasion (HR = 1.10, <i>p</i> < 0.001). Overall, patients who received RT showed increased median overall survival from 9.9 to 16.1 months (<i>p</i> < 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, <i>p</i> < 0.001) and HPV-negative patients (from 8.4 to 12.9 months, <i>p</i> = 0.0016) who received RT compared to those who did not. <b>Conclusions:</b> Primary-site radiotherapy may positively impact overall survival in limited metastatic OPC, irrespective of HPV status.