The impact of resection margins in hypopharyngeal surgery: a systematic review and meta-analysis

Abstract

Objective: Hypopharyngeal squamous cell carcinoma is an aggressive malignancy with poor prognosis due to frequently late-stage presentation and intrinsic anatomical complexity. Surgery remains a key treatment, and resection margins are crucial for local control and survival. However, achieving adequate margins is challenging due to submucosal tumour spread and common "skip lesions". This systematic review examines the impact of positive and close margins on oncological outcomes and their role in treatment planning. Methods: Following PRISMA guidelines, we included studies on adult hypopharyngeal cancer patients undergoing surgical treatment, including transoral laser microsurgery, transoral robotic surgery and open resections. The primary outcome was overall survival (OS); secondary outcomes included disease-free survival (DFS), disease-specific survival (DSS), and local control. A systematic search of PubMed, EMBASE, and Cochrane databases from 2000 to 2024 was conducted, with eligible studies screened based on strict inclusion criteria. Random-effect meta-analysis was used to estimate the pooled hazard ratio (HR) and relative 95% confidence interval (CI). Results: From an initial pool of 2,681 articles, 157 full-text studies were reviewed, and 7 met inclusion criteria. Data on 619 patients (mean age, 60.9 years) were analysed, all from retrospective studies. Among these, 17% received neoadjuvant chemotherapy, while 94% underwent adjuvant treatment due to positive margins or other adverse features. A meta-analysis found no statistically significant impact of positive or close margins on OS, DSS, or DFS when compared to negative ones. OS had an HR of 1.78 (95%CI: 0.79-4.04, p = 0.17), DFS HR 1.43 (95%CI: 0.82-2.49, p = 0.21), and DSS HR 1.31 (95%CI: 0.42-4.05, p = 0.42). Conclusions: This review underscores the challenges of achieving optimal margins in hypopharyngeal cancer surgery. While positive and close margins increase the risk of recurrence, their impact on survival remains unclear, emphasising the need for standardised margin assessment and tailored treatment strategies. The significant submucosal spread and presence of skip lesions necessitates a multidisciplinary approach. Future research should refine surgical techniques, improve intraoperative margin assessment, and optimise adjuvant therapy protocols to enhance oncologic outcomes.