Systemic immune-inflammation index as a prognostic biomarker across T-stage, biliary obstruction, and treatment setting in cholangiocarcinoma: A retrospective cohort study.

Abstract

137 Background: Cholangiocarcinoma (CCA) carries a dismal prognosis, and low-cost biomarkers applicable across disease stages and treatment settings remain an unmet need. The systemic immune-inflammation index (SII = neutrophils × platelets ÷ lymphocytes), calculated from standard CBC, combines three values into a composite inflammatory measure. While SII has been studied in surgical iCCA, its relationship with T-stage invasion depth, biliary obstruction, and prognosis in non-surgical CCA—representing >70% of patients—remains uncharacterized. Methods: Retrospective cohort of 93 CCA patients at Phramongkutklao Hospital, Bangkok (January 2020–July 2025); protocol approved by institutional Ethics Committee. Inclusion: histopathological or radiological CCA; SII, NLR, and CA 19-9 from peripheral blood within 30 days of diagnosis. Exclusion: concurrent malignancy, active cholangitis, immunosuppressive therapy. Markers analyzed as continuous variables (Mann-Whitney U; Kruskal-Wallis). Missing values excluded per variable. Potential confounders (subtype, stage, jaundice) noted descriptively. Three pre-specified analyses: (1) SII/NLR across T-substages (T1a–T4); (2) SII/NLR as outcome discriminators in non-surgical patients (n=68); (3) SII/NLR by jaundice (TB >2 mg/dL) across CCA subtypes. No correction for multiple comparisons; findings are hypothesis-generating. Results: Median age 60 years (29–91); 59% male; iCCA 74%, pCCA 14%, eCCA 12%; Stage IV 45%; surgery 27% (n=25). NLR rose stepwise from T1a (2.6) to T3/T4 (5.6); SII from 910 to 1,634. In non-surgical patients, SII was 3.7× higher in deceased versus alive-with-disease patients (1,680 vs. 451); NLR separated by 1.8× (5.1 vs. 2.8). Jaundice (TB >2 mg/dL) associated with markedly higher SII across all CCA subtypes (1,379 vs. 841); ALP quartile Q4 vs. Q1 showed 2.75× SII difference (see Table). Conclusions: SII tracks stepwise with T-stage depth, separates survival outcomes in the non-surgical majority more effectively than NLR, and is amplified by biliary obstruction across CCA subtypes. These data suggest SII captures both local tumor invasiveness and obstructive cholestatic inflammation, broadening its prognostic applicability beyond resected cohorts. Prospective validation incorporating multivariable survival analysis is warranted. SII and NLR by T-stage, non-surgical outcome, and biliary obstruction (n=93). Finding Group n NLR median SII median T-stage gradient T1a 18 2.6 910 T-stage gradient T2 54 3.9 1047 T-stage gradient T3/T4 12 5.6 1634 Non-surgical: outcome Died of disease 21 5.1 1680 Non-surgical: outcome Alive with disease 5 2.8 451 Biliary obstruction TB >2 mg/dL 30 5.0 1379 Biliary obstruction TB ≤2 mg/dL 63 3.5 841 ALP burden (Q1 vs Q4) Low vs High ALP 23 vs 24 2.7 vs 4.1 460 vs 1266