Advancing Education, Research, and Quality of Care for the Head and Neck oncology patient.
Program Number: AHNS03
Session Name: Scientific Session 1 - HPV-positive Oropharyngeal Disease
Session Date: Wednesday, May 14, 2025
Session Time: 11:15 AM - 12:00 PM
Neoadjuvant chemotherapy and transoral robotic surgery as definitive treatment in p16+ve oropharyngeal cancer: Outcomes of NECTORS trial
Nader Sadeghi, MD1; M Mascarella, MD1; K Richardson, MD1; A Zeitouni1; Jessica Hier, MD2; N. Golabi, MSc3; L Anthonanzas4; D Caglar1; K Sultanem, MD2; C Tsien, MD1; G Shenouda, MD1; K. Esfahani, MD2; A Mlynarek, MD2; M Hier, MD2; N Bouganim, MD1; 1McGill University Health Centre; 2McGill University; 3Research Institute of McGill University Health Centre; 4Jewish General HospitalBackground:
The treatment landscape for human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (HPV-OPSCC) is rapidly evolving, driven by the favorable prognosis of HPV-OPSCC, the advent of transoral robotic surgery (TORS), and the chronic and late toxicities of concurrent chemoradiotherapy (CCRT). Despite these advances, significant challenges persist: (1) mortality rates reach 30% in intermediate-risk HPV-OPSCC despite high-dose CCRT; (2) distant metastasis (DM) remains problematic, occurring in approximately 12–15% of patients treated with CCRT or TORS with adjuvant RT/CRT; (3) many patients receiving TORS upfront still require adjuvant RT/CRT, leading to long-term toxicity and limiting future salvage options; (4) upfront TORS is suboptimal for advanced primary tumors and is associated with adverse functional outcomes in cases requiring extensive surgery with adjuvant CCRT. To address these issues, we developed the NECTORS approach (NEoadjuvant Chemotherapy and TransOral Robotic Surgery) for HPV-OPSCC. This strategy incorporates systemic escalation with locoregional de-escalation, reserving RT/CRT for salvage therapy. Here, we report the 5-year results of the NECTORS trial (NCT04277858).
Methods: From 2017 to 2024, patients with AJCC-8 Stage I-III (previously AJCC-7 stage III and IVa) HPV-OPSCC were treated using the NECTORS protocol. Treatment involved three cycles of neoadjuvant chemotherapy (docetaxel and cisplatin), followed by TORS and selective neck dissection. Outcomes assessed included longitudinal patient-reported quality of life metrics (EORTC QLQ-C30, HN35, MDADI), pathologic response rates, and adjuvant RT/CRT utilization. Survival outcomes, relapse-free survival (RFS), disease-specific survival (DSS), and overall survival (OS), were evaluated using Kaplan-Meier analysis.
Results: Among the 145 patients treated with NECTORS, 83.4% were male with a mean (SD) age of 62.4 (8.3) years. Primary tumor sites included the tonsil (56.6%) and base of tongue (42.8%), with a minority (0.6%) of unknown origin. AJCC-8 staging distribution was 66.2% Stage I, 26.2% Stage II, and 7.6% Stage III. Notably, only 4 patients (2.7%) required adjuvant RT/CRT. There were 8 relapses (5.5%), 2.7% local and 2.7% regional sites, all successfully salvaged with CRT. The 5-year RFS, OS, and DSS rates were 94%, 99%, and 98.5%, respectively. Only one patient experienced DM, occurring post-regional relapse. Pathologic evaluation of neck dissections showed a complete response (cPR) in 58% and a major response (mPR) in 38%. Primary site responses were 69% cPR and 28% mPR. No residual disease was identified in at-risk neck zones. Progression-free survival (PFS) did not differ between node-positive and node-negative groups (p=0.8590) or between cPR and mPR groups (p=0.5572). All patients returned to their baseline quality of life and swallowing function.
Conclusions: The NECTORS approach demonstrates high efficacy in managing HPV-OPSCC, with 97.3% of patients spared adjuvant RT/CRT, minimizing the risk of distant metastasis while preserving quality of life. This strategy expands indications for TORS to include more advanced disease, successfully avoiding adjuvant RT/CRT in these cases. The low relapse rate, coupled with effective salvage using CRT, suggests NECTORS may enable selective neck dissection limited to involved neck zones, reducing the need for bilateral neck dissection in non-lateralized HPV-OPSCC. NECTORS represents a promising paradigm shift, offering a balanced approach of systemic escalation and locoregional de-escalation for HPV-OPSCC.