Outcomes for Potentially Resectable Patients Undergoing Primary Chemoradiation Treatment for T1 – T2 HPV Negative Oropharyngeal Squamous Cell Carcinoma

Abstract

Abstract Background A previous study in HPV-positive patients have shown that transoral surgical resectability (TOS) is a strong prognostic factor for patients with T1-2 disease undergoing radiotherapy (RT), but it is unclear whether this holds for HPV-negative patients, in whom the biology is different and outcomes are worse. We aimed to compare outcomes of potential TOS-candidates vs. non-TOS candidates, among patients who underwent RT/CRT for early T-stage human papillomavirus-negative (HPV-negative) OPSCC. Methods For patients treated with RT/CRT for early-stage HPV-negative OPSCC between 2014 and 2021, pretreatment imaging was reviewed by four head-and-neck surgeons, blinded to outcomes, to assess primary-site suitability for TOS, and extracapsular extension (ECE) was assessed by a head-and-neck neuroradiologist. We compared outcomes based on surgical resectability relating to: 1) the primary site tumor alone, and 2) the primary site plus the absence/presence of ECE (overall assessment). Kaplan-Meier curves for overall survival (OS), disease-specific survival (DSS), and progression-free survival (PFS) were compared using the log-rank test, with Cox regression for multivariable modeling. Results Seventy patients were included in the analysis. The mean age was 63.1 years and the majority of the patients were male 39/70 (55.7%). The primary site was TOS-favorable in 46/70 (66%). Based on the overall assessment (including the primary site and positive lymph nodes), 41/70 (58.6%) were TOS-favorable. The 3-year OS, DSS and PFS for primary site TOS-favorable vs. unfavorable were OS: 76.9% vs. 37.4%; DSS: 78.1% vs 46.2%, PFS: 69.9% vs 41.3%, (log-rank test = 0.01, 0.03, 0.04; respectively). Additionally, patients with an overall assessment of TOS favorability demonstrated better survival outcomes compared with TOS-unfavorable patients (OS: 77.3% vs. 46.2%; DSS: 78.2% vs. 56.5%, PFS: 72.3% vs. 42.1%, log-rank test = 0.01, 0.04, 0.01; respectively). Conclusion Patients with TOS-favorable HPV-negative early T-stage OPSCC have superior survival outcomes than TOS-unfavorable patients. This critical confounder needs to be considered when comparing primary surgical and primary radiation clinical trials and retrospective studies.