Prognostic utility of the Charlson comorbidity index in pancreatic cancer: a systematic review and meta‑analysis

The prognosis of pancreatic cancer is extremely poor, and patients frequently present with multiple comorbidities. The Charlson Comorbidity Index (CCI) and its age-adjusted version (CACI) are widely used to quantify the burden of comorbidity. This systematic review and meta-analysis aimed to evaluate the association between CCI/CACI and survival outcomes in patients with pancreatic cancer.

We systematically searched the Cochrane Library, Embase, PubMed, and Web of Science for relevant literature up to May 2025. Observational studies primarily investigating the association between CCI/CACI and overall survival (OS) in patients with pancreatic cancer were included. Two reviewers independently screened the literature, extracted data, and evaluated the quality of eligible studies using the Newcastle-Ottawa Scale. A random-effects model was employed to pool adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). Heterogeneity was assessed using the I² statistic. Subgroup analysis, sensitivity analysis, and regression analysis were also conducted.

This analysis incorporated 28 studies comprising 548,660 participants. Most of the studies were of high quality. The meta-analysis demonstrated that a higher CCI was associated with an inferior OS (pooled HR = 1.26, 95% CI: 1.09-1.47, P = 0.002). A similar association was observed for CACI (pooled HR = 1.40, 95% CI: 1.17-1.67, P < 0.001). Subgroup analyses confirmed that this association was generally consistent across different geographical regions, study designs, sample sizes, treatment modalities, and cut-off values of CCI. However, the assessment of heterogeneity revealed substantial heterogeneity in the analyses involving the CCI (I² = 63.6%, P = 0.005). Due to the limited number of eligible studies, quantitative synthesis could not be conducted for secondary endpoints, including progression-free survival and recurrence-free survival.

The current meta-analysis provides quantitative evidence from observational studies to support the CCI and CACI as factors associated with survival in patients with pancreatic cancer. However, given the substantial heterogeneity and observational design of the included studies, these indices should be interpreted as prognostic association markers rather than standalone clinical decision tools. The findings should be cautiously interpreted. Future prospective studies are required for validation. Integrated prediction models combining these indices with molecular markers should be explored.