Neoadjuvant chemotherapy followed by surgery versus definitive chemoradiotherapy in locally advanced head-and-neck cancer

Locally advanced head-and-neck squamous cell carcinomas pose a therapeutic challenge due to their complex anatomical presentation and high risk of recurrence. Two major curative strategies, neoadjuvant chemotherapy (NACT) followed by surgery and definitive chemoradiotherapy (CRT), are commonly employed, each with distinct advantages and limitations. NACT is primarily utilized in technically unresectable oral cavity cancers, where it facilitates downstaging and increases the likelihood of complete surgical resection. Several institutional and real-world studies have demonstrated that this approach improves resectability and survival in selected patients. Conversely, definitive CRT remains the standard of care for oropharyngeal, laryngeal, and hypopharyngeal cancers due to its proven efficacy in organ preservation and locoregional control, as evidenced by the meta-analysis of chemotherapy in head-and-neck cancer. However, both modalities are associated with considerable acute and late toxicities, underscoring the importance of individualized treatment planning. Subsite specificity, patient comorbidities, and tumor biology must inform modality selection. As ongoing trials refine indications and integrate biomarker-driven approaches, a multidisciplinary approach is still necessary to maximize oncologic and functional benefit.