NCT07369882

Comparison of Efficacy Between De-escalated Surgery and Standard Surgery After Neoadjuvant Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma

Comparison of Efficacy Between De-escalated Surgery and Standard Surgery After Neoadjuvant Immunotherapy in Locally Advanced Head and Neck Squamous Cell Carcinoma: A Randomized, Single-center Exploratory Clinical Study

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Qunxing Li,MD · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

This is a single-center, open-label, randomized, controlled, exploratory clinical trial designed to evaluate the efficacy and safety of de-escalated surgery compared with standard surgery in patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who achieved a partial response (PR) or complete response (CR) after neoadjuvant immunochemotherapy. Eligible patients will be randomly assigned in a 1:1 ratio to either the de-escalated surgery group (experimental) or the standard surgery group (control). The de-escalated surgery group will undergo limited tumor resection and selective neck dissection based on clinical and imaging response, while preserving important anatomical structures and functions when feasible. The control group will receive standard surgical treatment following NCCN guidelines. All patients will be evaluated using RECIST 1.1 criteria for radiological response and will undergo enhanced CT or MRI at baseline, before the second cycle of neoadjuvant therapy, within one week before surgery, 30 days after surgery, and every 3 months thereafter until 2 years post-surgery, disease recurrence, death, or study completion. The study aims to assess whether de-escalated surgery can achieve similar oncologic outcomes while improving postoperative function and quality of life. The primary endpoints are disease-free survival (DFS), health-related quality of life (HRQoL), and 3- and 5-year overall survival rates (OS rate). A total of 60 patients will be enrolled over a 3-year period, with 30 in each group.

Detailed description

This exploratory randomized controlled clinical study investigates the efficacy of de-escalated surgery versus standard surgery in patients with resectable locally advanced head and neck squamous cell carcinoma (LA-HNSCC) who have achieved partial response (PR) or complete response (CR) following neoadjuvant immunochemotherapy with a PD-1 inhibitor combined with nab-paclitaxel and carboplatin or cisplatin. The trial is designed to explore whether reducing the extent of surgical resection based on tumor response can maintain oncologic control while minimizing functional impairment. Patients who meet the inclusion criteria will be randomized 1:1 into two groups. The experimental group will receive de-escalated surgery, including: (1) primary tumor resection with ≥30% reduction in the resection margin diameter compared to pre-neoadjuvant dimensions, with an additional 10-15 mm margin beyond the shrunken tumor boundary; (2) preservation of vital structures such as the submandibular gland, mandible, epiglottis, oral commissure, parotid duct, eyeball, and major nerves when appropriate; and (3) de-escalated neck dissection, exempting patients with cN0 status before and after therapy or limiting dissection in selected nodal levels. The control group will undergo standard surgery according to NCCN guidelines, including wide local excision of the primary tumor (10-15 mm margin) and comprehensive neck dissection. Radiologic assessment will follow RECIST 1.1 using contrast-enhanced CT or MRI at multiple time points: baseline, prior to the second neoadjuvant cycle, within one week before surgery, 30 days postoperatively, and every three months up to 2 years or until recurrence, death, or study end. Baseline imaging will also rule out distant metastasis. Safety and postoperative follow-up will be conducted according to the same schedule. The study's endpoints are disease-free survival (DFS), health-related quality of life (HRQoL), and overall survival rates (OS rate) at 3 and 5 years. The trial plans to recruit 60 patients over three years, with 30 assigned to each arm. Results from this study may provide clinical evidence for the feasibility of precision-based, response-adapted de-escalated surgery in head and neck squamous cell carcinoma management, potentially improving postoperative function and patient quality of life without compromising survival outcomes.

Conditions

• Locally Advanced Head and Neck Squamous Cell Carcinoma

Interventions

Type	Name	Description
PROCEDURE	Radical surgery combined with radiotherapy or chemoradiotherapy	Radical resection of the primary tumor and neck dissection will be performed according to the NCCN guidelines, followed by adjuvant radiotherapy or chemoradiotherapy based on the postoperative pathological features.
PROCEDURE	Surgical De-escalation After Neoadjuvant Therapy	The experimental group will undergo a de-escalated surgical approach, defined as follows: 1. Primary tumor resection: The total diameter of the resection margins will be reduced by ≥30% compared with the pre-neoadjuvant therapy measurement. Resection will be performed with an additional 10-15 mm margin beyond the shrunken tumor boundary. 2. Functional preservation: When appropriate, important anatomical structures and functional components such as the submandibular gland, mandible, epiglottis, oral commissure, parotid duct, eyeball, and major nerves may be preserved after thorough evaluation. 3. De-escalated neck dissection: (1) Patients with clinically node-negative (cN0) neck status both before and after neoadjuvant immunotherapy will be exempted from neck dissection. (2) For midline-crossing lesions (e.g., tongue, hard palate, or soft palate), patients with contralateral clinically node-negative (cN0) neck status both before and after neoadjuvant immunotherapy will be exemp

Timeline

• Start date: 2026-01-12
• Primary completion: 2028-11-30
• Completion: 2030-01-31
• First posted: 2026-01-27
• Last updated: 2026-01-27

Locations

1 site across 1 country: China