Perioperative immunotherapy in resectable HNSCC: biological rationale to practical multidisciplinary implementation

Area of Science:

• Oncology
• Surgical Oncology
• Immunotherapy

Background:

• Immune checkpoint inhibition (ICI) is now a phase III strategy for resectable, locally advanced head and neck squamous cell carcinoma (HNSCC).
• Perioperative ICI significantly impacts surgical timing, neck management, reconstruction, and pathology workflows.

Purpose of the Study:

• To review phase III perioperative and neoadjuvant trials in resectable HNSCC.
• To focus on outcomes and practical considerations for surgeons and multidisciplinary teams (MDTs).
• To evaluate pathway timing, attrition, operability, safety, and response assessment feasibility.

Main Methods:

• Narrative review of phase III perioperative and key neoadjuvant studies in resectable HNSCC.
• Focus on outcomes and practical questions for surgeons and MDTs.
• Analysis of pathway timing, attrition, operability, safety, and response assessment.

Main Results:

• Phase III evidence supports neoadjuvant PD-1 followed by surgery and risk-adapted adjuvant therapy, improving event-free survival.
• Postoperative nivolumab with adjuvant chemoradiotherapy improves disease-free survival in high-risk patients.
• Short preoperative ICI is feasible without compromising resectability but requires strict timelines; surgical considerations include lymph node management and immune-related adverse events.

Conclusions:

• Perioperative ICI transforms HNSCC care into a tightly timed program.
• Successful implementation requires standardized pathology/radiology, MDT scheduling, and prospective registries.
• Optimal sequencing and salvage strategies after perioperative PD-1 exposure need further definition.