The relationship between circulating tumor biomarkers and prognosis of appendix cancer: A systematic review and meta-analysis.

BACKGROUND

The prognostic significance of circulating biomarkers in appendiceal neoplasms remains inconsistent across studies, hindering their clinical implementation for prognostic stratification. This meta-analysis aims to estimate and compare the prognostic value of various circulating biomarkers in appendiceal neoplasms.

MATERIALS AND

METHODS

We conducted a systematic literature search across PubMed, Web of Science, Cochrane Library, OVID platforms (Embase/MEDLINE) and Scopus from database inception to February 23, 2025, to identify studies investigating associations between circulating biomarkers and survival outcomes. Only retrospective cohorts are included. Hazard ratios (HRs) derived from Cox regression analyses were pooled using random-effects models. Newcastle-Ottawa Scale (NOS) was used to assess the quality of the studies. We performed pairwise and Bayesian network meta-analysis to establish prognostic hierarchy among biomarkers.

RESULTS

19 studies comprising 8478 patients evaluating six circulating biomarkers (CA125, CA19-9, CEA, Neutrophil-to-lymphocyte ratio (NLR), Platelet-to-lymphocyte ratio (PLR), and circulating tumor DNA (ctDNA)) were included. CA125 demonstrated independent prognostic value for both OS (HR=2.46[1.78-3.38, 95 % CI]) and DFS/PFS (HR=1.72[1.14-2.59, 95 % CI]), while CA19-9 specifically predicted DFS/PFS deterioration (HR=2.69[2.01-3.61, 95 % CI]). CEA elevation was independently associated with poorer OS (HR=2.04[1.45-2.88, 95 % CI]). ctDNA detection also showed prognostic value for adverse outcomes. Elevated NLR and PLR levels showed no significant associations with survival outcomes. Bayesian network analysis revealed no significant differences.

CONCLUSIONS

Preoperative elevation of serum CA125, CA19-9, and CEA levels demonstrates significant prognostic value in appendiceal neoplasms. While ctDNA retains prognostic significance, inflammatory markers NLR and PLR show limited clinical utility.