What is a short summary of the ORATOR trial comparing primary radiotherapy versus trans‑oral robotic surgery for early‑stage HPV‑positive oropharyngeal squamous cell carcinoma?

ORATOR Trial Summary

The ORATOR trial demonstrated that primary radiotherapy resulted in superior swallowing quality of life at 1 year compared to transoral robotic surgery (TORS) for early-stage oropharyngeal cancer, though this difference diminished over time and did not reach clinically meaningful thresholds, with both approaches showing equivalent oncologic outcomes. 1

Trial Design and Patient Population

• Phase II randomized controlled trial enrolling 68 patients with T1-T2, N0-2 (≤4 cm) oropharyngeal squamous cell carcinoma between August 2012 and June 2017 2, 3
• Patients were randomly assigned 1:1 to either:
  • Radiotherapy arm (n=34): 70 Gy with concurrent chemotherapy if node-positive 3
  • TORS arm (n=34): Transoral robotic surgery plus neck dissection with or without adjuvant therapy based on pathologic findings 3
• The trial was conducted at six hospitals across Canada and Australia 3

Primary Endpoint: Swallowing Quality of Life

• Primary endpoint was swallowing-related quality of life at 1 year measured by the MD Anderson Dysphagia Inventory (MDADI) 1, 3
• At 1 year: Mean MDADI scores were 86.9 in the RT arm versus 80.1 in the TORS arm (p=0.042), favoring radiotherapy 3
• However, this 6.8-point difference did not meet the pre-specified 10-point threshold for a clinically meaningful change 3
• Long-term follow-up at median 45 months showed the swallowing quality of life difference persisted but decreased over time (p=0.049 on longitudinal analysis) 4
• By 5 years (median follow-up 5.1 years), MDADI total scores converged and were not significantly different across the entire follow-up period (p=0.11) 1, 2

Secondary Outcomes: Toxicity Profiles

Radiotherapy Arm Toxicities

• More neutropenia: 18% versus 0% in TORS arm 3
• More hearing loss: 38% versus 15% in TORS arm (p<0.05) 1, 3
• More tinnitus: 35% versus 6% in TORS arm 3
• Worse xerostomia (dry mouth): Significantly worse over time (p=0.032) 1, 2

TORS Arm Toxicities

• More trismus: 26% versus 3% in RT arm 3
• More dysphagia: Grade 2-5 dysphagia more common (p<0.05) 1
• More pain: Significantly worse pain scores (p=0.002) 1, 2
• One treatment-related death from post-operative bleeding 3
• More dental concerns at 1 year, though these resolved by years 2-3 4

Overall Adverse Event Rates

• Grade 2-5 adverse event rates did not differ significantly between arms: 91% (RT) versus 97% (TORS), p=0.61 1, 2

Oncologic Outcomes

• No differences in overall survival or progression-free survival between the two treatment arms 1, 2
• Excellent oncologic outcomes were achieved in both arms 2
• Median follow-up of 5.1 years demonstrated sustained disease control in both groups 1, 2

Quality of Life Beyond Swallowing

• EORTC QLQ-C30 and H&N35 scores showed differing profiles between arms 1, 2
• Pain concerns in the TORS arm that were prominent at 1 year resolved by years 2-3 4
• Nutritional supplement use increased in TORS patients at 3 years (p=0.015) 4
• Dry mouth remained persistently worse in the RT arm throughout follow-up (p=0.041) 4

Clinical Implications and Guideline Integration

• ASCO 2025 guidelines cite ORATOR as key evidence that MDADI total scores converge by 5 years with no statistically significant difference across the follow-up period 1
• EHNS-ESMO-ESTRO 2020 guidelines reference ORATOR as demonstrating no quality of life advantage at 2 years when TORS was compared with radiotherapy 1
• Both treatment modalities are considered standard options for early-stage oropharyngeal cancer (T1-T2, N0-N1) 1
• Treatment selection should remain a shared decision between patient and providers, as toxicity and quality of life profiles differ in specific domains while oncologic outcomes are equivalent 2

Important Caveats

• Many TORS patients required adjuvant therapy: A substantial proportion received postoperative radiotherapy or chemoradiotherapy based on pathologic findings, making it difficult to isolate the "true" quality of life outcomes from surgery alone 5
• The trial was not powered to detect differences in survival outcomes, only quality of life differences 3
• Patient selection matters: The trial enrolled only early-stage disease (T1-T2, N0-2 ≤4 cm), and results may not apply to more advanced cases 3
• The 10-point MDADI threshold for clinically meaningful change was never achieved, despite statistical significance at 1 year 3