Prognostic determinants of survival in gastroenteropancreatic neuroendocrine tumors: A real-world evaluation of age, stage, grade, and Ki-67 dynamics.

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are clinically heterogeneous, and accurate prognostic assessment is crucial. Although Ki-67 is a core element of the WHO classification, its prognostic performance varies across real-world cohorts. We evaluated the prognostic value of age, stage, WHO grade, and Ki-67 using multiple modeling strategies in a mature single-center GEP-NET cohort.

METHODS: patients with histologically confirmed GEP-NETs diagnosed between 2000 and 2024 at a tertiary academic center were evaluated. Eligible tumors arose in the small bowel, pancreas, stomach, colon, rectum, duodenum, or appendix. Overall survival (OS) was calculated from diagnosis. Survival was assessed using Kaplan-Meier estimates, univariate Cox models, and three multivariable Cox models incorporating Ki-67 as a continuous, categorical, or spline-transformed variable.

RESULTS: A total of 103 patients were included. Median follow-up was 99.5 months, with 40 deaths. Higher WHO grade predicted worse OS (G3 vs G1 HR 4.38, 95 percent CI 1.45-13.18). Age and stage were significant prognostic variables and remained independently associated with OS. Ki-67 showed expected biological patterns but was not an independent linear predictor; spline models indicated possible nonlinear effects.

CONCLUSIONS: Age, stage, and WHO grade were the strongest predictors of OS. Ki-67 demonstrated biologically consistent but statistically complex behavior, highlighting the need for refined modeling and standardized reporting.