Prognostic impact of the IASLC grading system of lung adenocarcinoma: a systematic review and meta-analysis

Aims: Tumour grading is an essential part of the pathologic assessment that promotes patient management. The International Association for the Study of Lung Cancer (IASLC) proposed a grading system for non-mucinous lung adenocarcinoma in 2020. We aimed to validate the prognostic impact of this novel grading system on overall survival (OS) and recurrence-free survival (RFS) based on literature data. Methods and Results: The review protocol was registered in PROSPERO (CRD42023396059). We aimed to identify randomized or non-randomized controlled trials published after 2020 comparing different IASLC grade categories in Medline, Embase, and CENTRAL. Hazard ratios (HRs) with 95% confidence intervals (CIs) of OS and RFS were pooled and the Quality In Prognosis Studies (QUIPS) tool was used to assess the risk of bias in the included studies. Ten articles were eligible for this review. Regarding OS estimates, grade 1 lung adenocarcinomas were better than grade 3 both in univariate and multivariate analyses (HROSuni = 0.19, 95% CI: 0.05-0.66, p = 0.009; HROSmulti = 0.21, 95% CI: 0.12-0.38, p < 0.001). Regarding RFS estimates, grade 3 adenocarcinomas had a worse prognosis than grade 1 in multivariate analysis (HRRFSmulti: 0.22, 95% CI: 0.14-0.35, p < 0.001). Conclusion: The literature data and the result of our meta-analysis demonstrate the prognostic relevance of the IASLC grading system. This supports the inclusion of this prognostic parameter in daily routine worldwide.