Introduction Head and neck cancer (HNC) significantly affects patients worldwide, often resulting in physical disfigurement, functional impairment, and diminished quality of life (QoL). Advanced HNC may necessitate reconstructive surgeries using free tissue transfer, which, despite improving survival, can exacerbate emotional and social challenges such as anxiety, depression, and social isolation. This study aims to evaluate the well-being of patients undergoing free flap surgery for advanced HNC using validated tools. Methods We conducted a prospective longitudinal study of 30 patients with advanced HNC (≥T3, stage ΙΙΙ-IV) who underwent free flap reconstructive surgery at the General Oncological Anticancer Hospital of Athens 'Agios Savvas' between January 2018 and January 2024. Patient-reported outcomes were assessed using three validated questionnaires in Greek: the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module (EORTC QLQ-H&N35), the Hospital Anxiety and Depression Scale (HADS), and the Brief Pain Inventory (BPI). Statistical analysis was performed using IBM SPSS Statistics for Windows, version 26.0 (IBM Corp., Armonk, NY), with statistical significance set at p < 0.05. Results Among the 30 patients (10 women and 20 men; mean age = 56.6 years), post-surgical assessments indicated significant worsening of symptoms, including increased pain (p < 0.001), swallowing difficulties (p < 0.001), and speech impairments (p < 0.001). Nearly all patients reported increased analgesic use post surgery (p = 0.003), and a significant correlation was found between pain severity and diminished daily functioning, particularly life enjoyment (correlation coefficient = 0.788, p < 0.001). Additionally, 63% of patients (n = 19) were diagnosed with depression and 67% with anxiety (n = 20), with men showing a higher prevalence of depression (p = 0.001). No significant differences in anxiety rates were found between the sexes. Overall, pain severity had a broad impact on both physical and psychological status, contributing to social withdrawal and isolation. Conclusions Patients with HNC who undergo free flap reconstructive surgery face significant challenges in emotional, social, and physical well-being. Depression and anxiety are common but often undetected, especially in men. Pain remains a significant factor affecting QoL and social engagement. Comprehensive care models, including standardized pre- and post-treatment assessments, early mental health screenings, and personalized rehabilitation strategies, are essential to improve outcomes and enhance QoL for HNC patients.
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