Serum CA19.9 for Detecting High-Grade Dysplasia and Invasive Carcinoma in Patients With Intraductal Papillary Mucinous Neoplasm: A Systematic Review and Meta-Analysis.

IMPORTANCE

Current guidelines recommend routine assessment of serum carbohydrate antigen 19.9 (CA19.9) at diagnosis and during follow-up of patients with intraductal papillary mucinous neoplasm (IPMN) to detect high-grade dysplasia (HGD) and invasive carcinoma (IC). Guidelines consider an elevated serum CA19.9 level (≥37 U/mL) a worrisome feature and a relative indication for surgery.

OBJECTIVE

To evaluate the diagnostic accuracy of CA19.9 for identifying patients with IPMN at high risk of HGD and IC.

DATA SOURCES: PubMed, Embase (Ovid), and Web of Science databases (inception to March 1, 2025).

STUDY SELECTION: Studies reporting on diagnostic accuracy of CA19.9 (cut-off 37 U/mL) in patients with resected IPMN.

DATA EXTRACTION AND SYNTHESIS: Data extraction was completed by 3 reviewers (March to December 2025). Risk of bias was assessed using the QUADAS-2 tool and evidence certainty with Grading of Recommendations Assessment, Development and Evaluation. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Diagnostic Test Accuracy Studies reporting guidelines and the Cochrane Diagnostic Test Accuracy protocol were applied for overall conduct. A random-effects meta-analysis was conducted in December 2025 to obtain a pooled estimate of diagnostic accuracy. Main pancreatic duct involvement and rate of HGD or IC were assessed using meta-regression. Summary receiver operating characteristics curves were generated. The area under the curve (AUC) was calculated as overall test performance.

MAIN OUTCOMES AND MEASURES: Diagnostic accuracy of serum CA19.9 (≥37 U/mL), reported as pooled sensitivity, specificity, positive likelihood ratio (PLR) and negative likelihood ratios (NLR), diagnostic odds ratio (DOR), and AUC and their 95% CIs. Pathology was considered as reference standard.

RESULTS

Overall, 24 studies assessing 5281 patients with IPMN were included. Mean age was 64.7 (95% CI, 62.24-67.10) years, and 2919 patients (55%) were male. Serum CA19.9 data were available for 4653 patients (88.1%), with 966 patients (20.8%) showing elevated levels. Pooled estimates of diagnostic accuracy for HGD or IC (present in 1939 patients [41.7%]) demonstrated sensitivity of 0.35 (95% CI, 0.29-0.43), specificity of 0.90 (95% CI, 0.87-0.92), PLR of 3.37 (95% CI, 2.56-4.44), NLR of 0.72 (95% CI, 0.65-0.80), DOR of 4.67 (95% CI, 3.26-6.70), and AUC of 0.78 (95% CI, 0.74-0.82).

CONCLUSIONS AND RELEVANCE: In this systematic review and meta-analysis, CA19.9 with the current cutoff (37 U/mL) demonstrated poor performance in excluding HGD or IC and only modest value for ruling in IC. These findings suggest CA19.9 should not be used as a standalone or screening test, while its limited rule-in value may aid decision-making in patients with moderate pretest probability. Future studies should investigate whether different cutoffs and dynamic trends could improve diagnostic accuracy.