OBJECTIVE: Transoral robotic surgery (TORS) has shown promising results in treating human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), and there has been increasing interest in incorporating neoadjuvant chemotherapy (NCT) prior to TORS. This study aimed to assess the feasibility and safety of sparing adjuvant RT following NCT and TORS. METHODS: A retrospective cohort study included consecutive patients with HPV-positive OPSCC who underwent NCT followed by TORS without adjuvant RT. Disease-free survival (DFS) was the primary outcome. Pattern of recurrence (local, regional, and distant), salvage treatment outcomes, and predictors of tumor recurrence were also assessed. RESULTS: A total of 84 patients were included in the analysis. No patients died during the study period. DFS rates (95% Confidence Interval, CI) at 1, 2, and 3 years were 92.8% (87.4-98.5), 87.0% (79.7-94.9), and 84.4% (76.0-93.8), respectively. Local, regional, and distant recurrence rates were 7.0%, 9.5%, and 3.6%, respectively. Salvage treatment achieved a 100% salvage rate. Predictors of tumor recurrence included the number of positive lymph nodes (hazard ratio: 2.66; 95% CI: 1.19-5.92) and clinical stage III at diagnosis (hazard ratio: 7.65; 95% CI: 1.97-29.7). CONCLUSIONS: Recommendation of adjuvant treatment based on pathologic adverse features appears to be associated with favorable outcomes in selected HPV-positive OPSCC cases treated with NCT and TORS. Future studies should focus on refining criteria for recommending adjuvant RT to further reduce recurrence rates and minimize treatment-related toxicity, contributing to personalized treatment strategies for HPV-related OPSCC. LEVEL OF EVIDENCE: 4 Laryngoscope, 135:1401-1408, 2025.
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