Initial surgical versus non-surgical treatments for advanced hypopharyngeal cancer: A meta-analysis with trial sequential analysis

Background: There is no consensus on whether initial surgical or non-surgical treatments should be the standard treatment pattern for advanced hypopharyngeal cancer. The aim of the meta-analysis was systematically and quantitatively compare the relative efficacy between initial surgical and non-surgical therapies in patients with advanced-stage hypopharyngeal carcinoma. Methods: A comprehensive search was performed in PubMed, the ISI Web of Knowledge, the Cochrane Library, and Embase databases from inception to April 10, 2019. Citation screening, data abstraction and quality assessment were performed in duplicate. Meta-analysis with trial sequential analysis (TSA) was used to assess the primary and secondary outcomes. Besides, we used the Grading of Recommendations Assessment Development and Evaluation (GRADE) to evaluate the certainty of the body of evidence. Results: A total of 17 trials was appraised with 2539 patients that complied with inclusion and exclusion criterion. Pooled analyses indicated patients receiving primary surgical and non-surgical therapy did not significantly differ in overall survival (OS) (relative risk [RR] = 1.04, 95% confidence interval [CI] = 0.94 to 1.15), with TSA inconclusive. Additionally, patients treated with primary surgical experienced an increased disease free survival (DFS) probability compared with non-surgical treatment (RR 1.20, 95% CI = 1.05 to1.37), while TSA is inconclusive. Notably, non-surgical management did have a beneficial efficacy on larynx preservation (RR 0.48, 95% CI = 0.33 to 0.70), and TSA also provided conclusive evidence. GRADE indicated the level of evidence was low or very low for primary or secondary outcomes. Conclusion: The results of our meta-analysis indicated when compared to surgical treatments, non-surgical therapy for patients with advanced hypopharyngeal carcinoma appears to have equivalent efficacy, and it offers an opportunity to preserve laryngeal function. Due to inconclusive evidence by TSA, further investigation with large randomized clinical trials (RCTs) using modern approaches should be undertaken to verify the results of this meta-analysis.