Prognostic value of tertiary lymphoid structures (TLS) in digestive system cancers: a systematic review and meta-analysis

Background Existing literature suggests that tertiary lymphatic structure (TLS) is associated with the progression of cancer. However, the prognostic role of TLS in digestive system cancers remains controversial. This meta-analysis aims to synthesize currently available evidence in the association between TLS and the survival of digestive system cancers. Methods We systematically searched three digital databases (PubMed, Embase, Web of Science) for articles published from database inception to December 23, 2022. Study selection criteria are based on PECO framework: P (population: patients with digestive system cancers), E (exposure: presence of TLS), C (comparator: absence of TLS), O (outcome: overall survival, OS; recurrence-free survival, RFS; disease-free survival, DFS). The Quality in Prognostic Studies (QUIPS) tool was used to assess risk of bias for included studies. The study protocol was registered with PROSPERO (CRD42023416307). Results A total of 25 studies with 6910 patients were included into the final meta-analysis. Random-effects models revealed that the absence of TLS was associated with compromised OS, RFS, and DFS of digestive system cancers, with pooled hazard ratios (HRs) of 1.74 (95% CI: 1.50–2.03), 1.96 (95% CI: 1.58–2.44), and 1.81 (95% CI: 1.49–2.19), respectively. Subgroup analyses disclosed a stronger TLS-survival association for pancreatic cancer, compared with other digestive system cancers. Conclusion TLS may be of prognostic significance for digestive system cancers. More original studies are needed to further corroborate this finding.