The prognostic value of TMB in early-stage non-small cell lung cancer: a systematic review and meta-analysis

BACKGROUND: Tumor mutation burden (TMB) has been validated as a predictive biomarker for immunotherapy response and survival in numerous cancer types. Limited data is available on the inherent prognostic role of TMB in early-stage tumors. OBJECTIVE: To evaluate the prognostic role of TMB in early-stage, resected non-small cell lung cancer (NSCLC). DESIGN: Systematic review and meta-analysis of pertinent prospective and retrospective studies. DATA SOURCES AND METHODS: Publication search was performed in PubMed, Embase, Cochrane Library, and Web of Science databases. Based on the level of heterogeneity, a random- or fixed-effects model was used to calculate pooled effects of hazard ratio (HR) for overall survival (OS) and disease-free survival (DFS). The source of heterogeneity was investigated using sensitivity analysis, subgroup analysis, and publication bias assessment. RESULTS: Ten studies comprising 2520 patients were included in this analysis. There was no statistically significant difference in OS (HR, 1.18, 95% CI, 0.70, 1.33; p 0.53, I(2) = 80%; p(het) < 0.0001) and DFS (HR, 1.18, 95% CI, 0.91, 1.52; p = 0.53, I(2) = 75%; p(het) = 0.0001) between the high-TMB and low-TMB group. Subgroup analyses indicated that East Asian ethnicity, and TMB detected using whole exome sequencing, and studies with <100 patients had poor DFS in the high-TMB group. CONCLUSION: The inherent prognostic role of TMB is limited in early-stage NSCLC. Ethnic differences in mutation burden must be considered while designing future trials on neoadjuvant immunotherapy. Further research in the harmonization and standardization of panel-based TMB is essential for its widespread clinical utility. Registration: CRD42023392846.