Prognostic Value of Tertiary Lymphoid Structures in Stage I Nonsmall Cell Lung Cancer: Does Location Matter?

Emerging evidence indicates the importance of tertiary lymphoid structures (TLSs) in predicting the outcomes of nonsmall cell lung cancer (NSCLC) patients; however, their prognostic value and correlations with peripheral inflammatory prognostic indices in stage I patients have been less well studied.

Stage I NSCLC patients were recruited retrospectively; the presence and location of TLSs (peritumoral [pTLSs] and intratumoral [iTLSs]) were determined via hematoxylin and eosin (H&E)-stained slides. Peripheral inflammatory indices, including the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), prognostic nutritional index (PNI), and advanced lung cancer inflammation index (ALI), were obtained and compared among these subgroups. Disease-free survival (DFS) and overall survival (OS) were tested via Kaplan-Meier analysis, and risk factors for survival were determined via a Cox proportional hazards model.

A total of 24.73% and 92.73% of patients were positive for pTLSs and iTLSs, respectively. The absolute number of iTLSs was significantly greater than that of pTLSs (P < .001). Low preoperative LMR and ALI were detected only in patients with pTLSs but not in those without. Only pTLS was found to be a risk factor for both DFS and OS, and it was independently associated with OS (HR = 3.93, 95% confidence interval [CI] = 1.16-13.37; P = .028). Accordingly, patients with pTLSs had relatively poor DFS (log rank = 5.46, P = .019) and OS (log rank = 10.48, P = .001) rates.

Among the heterogeneous results concerning the prognostic value of pTLSs and iTLSs in stage I NSCLC, our results for the first time indicated that the presence of pTLSs may predict poor outcomes in these patients and no correlation of iTLSs with the outcomes was validated; however, additional studies with large sample size are needed in future.