Surgical Considerations for Head and Neck Squamous Cell Cancer Patients after Neoadjuvant Chemotherapy

Background/Objectives: Neoadjuvant chemotherapy (NACT) has re-emerged as a promising strategy in the management of head and neck squamous cell carcinoma (HNSCC), offering potential benefits in tumor downstaging, early eradication of micrometastases, and facilitation of function-preserving surgical approaches. With the increasing adoption of minimally invasive techniques such as transoral robotic surgery (TORS), the integration of NACT into surgical treatment pathways has gained renewed interest. However, the incorporation of NACT introduces important surgical considerations, including optimal timing of resection, intraoperative technical challenges, pathologic assessment of treatment response, and implications for postoperative therapy.Materials & Methods: A narrative review was conducted focusing on recent clinical trials, systematic reviews, and meta-analyses addressing NACT in HNSCC, with emphasis on surgical timing, technical considerations, complications, and oncologic outcomes.Results: NACT can induce tumor downstaging and improve R0 resection rates, with recent studies reporting high objective response rates and favorable pathological responses. However, its impact on overall survival remains inconsistent across studies. Surgical considerations include optimal timing after chemotherapy, tissue fibrosis and edema, altered anatomical planes, and perioperative complications. Meta-analyses suggest that while NACT does not significantly increase major surgical complications, variability exists depending on regimen and patient selection. In HPV-positive oropharyngeal cancer, NACT followed by TORS has demonstrated reduced pathological staging with comparable survival outcomes, supporting its role as a de-escalation strategy. Emerging strategies combining NACT with immunotherapy, including the phase 3 KEYNOTE-689 trial demonstrating improved event-free survival with perioperative pembrolizumab, are further reshaping surgical planning.Conclusion: NACT plays a growing but still selective role in HNSCC. Careful patient selection, multidisciplinary coordination, and awareness of altered surgical fields are essential to maximize benefits while minimizing risks.