Randomized Trial of Radiotherapy Versus Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma: Long-Term Results of the ORATOR Trial

Abstract

PURPOSE The incidence of oropharyngeal squamous cell carcinoma (OPSCC) has risen rapidly, because of an epidemic of human papillomavirus infection. The optimal management of early-stage OPSCC with surgery or radiation continues to be a clinical controversy. Long-term randomized data comparing these paradigms are lacking. METHODS We randomly assigned patients with T1-T2, N0-2 (≤ 4 cm) OPSCC to radiotherapy (RT) (with chemotherapy if N1-2) versus transoral robotic surgery plus neck dissection (TORS + ND) (with or without adjuvant therapy). The primary end point was swallowing quality of life (QOL) at 1-year using the MD Anderson Dysphagia Inventory. Secondary end points included adverse events, other QOL outcomes, overall survival, and progression-free survival. All analyses were intention-to-treat. Herein, we present long-term outcomes from the trial. RESULTS Sixty-eight patients were randomly assigned (n = 34 per arm) between August 10, 2012, and June 9, 2017. Median follow-up was 45 months. Longitudinal MD Anderson Dysphagia Inventory analyses demonstrated statistical superiority of RT arm over time ( P = .049), although the differences beyond 1 year were of smaller magnitude than at the 1-year timepoint (year 2: 86.0 ± 13.5 in the RT arm v 84.8 ± 12.5 in the TORS + ND arm, P = .74; year 3: 88.9 ± 11.3 v 83.3 ± 13.9, P = .12). These differences did not meet the threshold to qualify as a clinically meaningful change at any timepoint. Certain differences in QOL concerns including more pain and dental concerns in the TORS + ND arm seen at 1 year resolved at 2 and 3 years; however, TORS patients started to use more nutritional supplements at 3 years ( P = .015). Dry mouth scores were higher in RT patients over time ( P = .041). CONCLUSION On longitudinal analysis, the swallowing QOL difference between primary RT and TORS + ND approaches persists but decreases over time. Patients with OPSCC should be informed about the pros and cons of both treatment options (ClinicalTrials.gov identifier: NCT01590355 ).

NCCN Guidelines® Insights: Head and Neck Cancers, Version 1.2022

“…Swallowrelated QoL outcomes reached statistical significance favoring the primary RT cohort; however, this difference did not meet criteria for a clinically meaningful change, and with long-term follow-up the difference in scores became less pronounced with the passage of time. 64,65 Study results showed that there were excellent and similar PFS and OS rates in both arms. The authors concluded that "RTand TORS-based approaches were associated with clinically similar QoL outcomes, but differing spectra of toxicities, and differences in QoL between arms decreased over time.…”

“…Clinicians and patients should be involved in shared decisionmaking, in a multidisciplinary context, to individualize treatment of oropharyngeal squamous cell carcinoma." 65 Additional randomized trials of minimally invasive transoral surgery or RT for oropharyngeal cancer are ongoing or have been presented in abstract form (ClinicalTrials.gov identifiers: NCT02984410, NCT05144100, and NCT03210103 66 ).…”

18F-Fluorodeoxyglucose Positron Emission Tomography of Head and Neck Cancer: Location and HPV Specific Parameters for Potential Treatment Individualization

“…This is an important observation for future aims to personalize radio-oncological treatment by the implementation of PET parameters. In early stage OPC, radiotherapy and transoral robotic surgery showed comparable quality of life and outcome, but with different toxicity profiles in a randomized phase-II study ( 22 , 23 ). Although high-level evidence is lacking for other and more advanced HNSCC, CRT and primary surgery are often considered similar efficient primary treatment approaches.…”

The effect of human papillomavirus status on prognosis and local treatment strategies of T1-2N0 oropharyngeal squamous cell cancer

“…In our cohort, the trend that radical surgery was the first choice for the majority of patients (57.1–64.7%) was stable over time. The ORATOR study compared the quality of life (QOL) and survival outcome between TORS and radiotherapy (RT) for T1-T2N0-2 OPSCC patients (88% of patients had HPV-related tumors) ( 36 ). Longitudinal QOL scores were statistically superior after radiotherapy.…”