Neutrophil-to-Lymphocyte Ratio as a Prognostic Biomarker in Pancreatic Neuroendocrine Neoplasms

Background: Pancreatic neuroendocrine neoplasms (PNENs) represent a rare, heterogeneous group of tumors with highly variable clinical outcomes. While standard clinicopathological parameters like World Health Organization (WHO) grading and TNM staging provide critical prognostic data, they do not fully explain the survival disparities observed in patients with similar tumor characteristics. This narrative review evaluates the clinical and prognostic significance of the neutrophil-to-lymphocyte ratio (NLR)—a widely accessible marker of systemic inflammation—in patients with PNENs. Methods: A comprehensive literature review was conducted to synthesize current evidence regarding the prognostic utility of peripheral NLR levels. Results: Studies conducted specifically in pancreatic neuroendocrine tumors (PNETs) suggest that elevated peripheral blood NLR is associated with adverse clinicopathological features and, in several cohorts, with shorter overall survival (OS) and recurrence-free survival (RFS). However, the strength and independence of these associations vary across studies. Evidence from mixed gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN) cohorts undergoing systemic treatment or peptide receptor radionuclide therapy (PRRT) provides complementary insights into the predictive capacity of NLR regarding treatment response, though it remains indirect evidence for PNETs, particularly when pancreatic-specific subgroup results are unavailable. Differences in tumor differentiation, grade, stage, treatment setting, and NLR cut-off values limit direct comparisons across studies. Conclusions: NLR is an accessible, candidate adjunctive prognostic biomarker in PNETs, particularly in surgically treated populations. However, the evidence remains highly heterogeneous, and its clinical utility and standardized thresholds remain unvalidated. Proposed applications in treatment selection or surveillance intensity should be strictly regarded as investigational and hypothesis-generating, rather than validated clinical strategies. NLR should complement, rather than replace, established clinicopathological prognostic factors.