Abstract
BACKGROUND: Introduced by the International Association for the Study of Lung Cancer (IASLC) in 2005, uncertain resection (Run) categorizes a new subclass of residual tumor. Despite several studies, the prognostic significance of Run in operable non-small cell lung cancer (NSCLC) remains unclear. OBJECTIVES: This study aimed to investigate the prognostic influence of Run in operable NSCLC, focusing on the impact of the four elements that comprise R descriptors on patient survival. DESIGN: A systematic review and meta-analysis were conducted to synthesize data from relevant clinical studies. METHODS: We developed search strategies to identify relevant clinical studies across databases including PubMed, Embase, Cochrane Library, Web of Science, CNKI, and Wanfang up to June 2024. Quantitative analysis was performed with Stata 15 to investigate the prognostic influence of Run, the extent of mediastinal lymph node removal, and the highest mediastinal lymph node involvement (HMLI). We also summarized the main findings from studies on pleural lavage cytology (PLC) and carcinoma in situ in operable NSCLC. RESULTS: Compared to complete resection, Run-associated patients exhibited inferior 5-year overall survival (OS) and disease-free survival (DFS; risk ratio (RR) = 1.31, 95% confidence interval (CI) 1.19-1.44; RR = 1.43, 95% CI 1.28-1.60). Limited lymphadenectomy (L-LA) in cI stage showed similar survival benefit (OS, RR = 0.97, 95% CI 0.90-1.06; DFS, RR = 1.06, 95% CI 0.97-1.15), in contrast with systematic lymph node dissection (SLND). For pN2-III patients, HMLI indicated poorer OS (hazard ratio (HR) = 1.22, 95% CI 1.14-1.31) and DFS (HR = 1.25, 95% CI 1.14-1.36). CONCLUSION: IASLC's residual tumor classification correlated with significant survival differences. Compared with R0, Run was associated with inferior 5-year OS and DFS. L-LA seemed to provide equivalent survival benefits, in contrast to SLND. For patients with low invasiveness in stage cI, L-LA could be considered as a preferred option. HMLI predicts poorer survival in pN2-III patients, and positive PLC significantly worsened long-term survival in operable NSCLC, particularly at early stage.