Diagnostic Accuracy of Serum CA19-9 in Patients with Cholangiocarcinoma: A Systematic Review and Meta-Analysis

Abstract

BackgroundCholangiocarcinoma (CCA) is a relatively rare cancer worldwide; however, its incidence is extremely high in Asia. Numerous studies reported that serum carbohydrate antigen 19-9 (CA19-9) plays a role in the diagnosis of CCA patients. However, published data are inconclusive. The aim of this meta-analysis was to provide a systematic review of the diagnostic performance of CA19-9 for CCA.Material/MethodsWe searched the public databases including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases for articles evaluating the diagnostic accuracy of serum CA19-9 to predict CCA. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software.ResultsA total of 31 articles met the inclusion criteria, including 1,264 patients and 2,039 controls. The pooled SEN, SPE, PLR, NLR, and DOR were 0.72 (95% CI: 0.70–0.75), 0.84 (95% CI: 0.82–0.85), 4.93 (95% CI, 3.67–6.64), 0.35 (95%CI, 0.30–0.41), and 15.10 (95% CI, 10.70–21.32), respectively. The area under SROC curve was 0.8300. The subgroup analyses based on different control type, geographical location, and sample size revealed that the diagnostic accuracy of CA19-9 tends to be same in different control type, but showed low sensitivity in European patients and small size group.ConclusionsSerum CA19-9 is a useful non-invasive biomarker for CCA detection and may become a clinically useful tool to identify high-risk patients.

Serum Metabolites as Diagnostic Biomarkers for Cholangiocarcinoma, Hepatocellular Carcinoma, and Primary Sclerosing Cholangitis

“…However, its specificity is low, because this biomarker is also elevated in one third of patients with PSC without biliary cancer, and in other liver diseases and tumors; in addition, there is an important heterogeneity in its elevation in patients with iCCA . Moreover, the sensitivity of this cancer biomarker is compromised by the fact that ~10% of the population does not produce CA 19‐9 . On the other hand, AFP provides low diagnostic capacity for HCC and is therefore not recommended for screening or diagnosis in Western guidelines…”

Circulating Biomarkers for Cholangiocarcinoma

“…primary sclerosing cholangitis, PSC). Receiver operating characteristic curve analysis revealed an area under the curve (AUC) of 0.83 [15]. In addition, the inability to produce CA19–9 in patients with Lewis-null blood type further increases the number of false negative test results [16, 17].…”

Surveillance in cholangiocellular carcinoma

“…As the most prominent example, levels of the tumour marker CA19-9 have been measured in patients with suspected CCA to define a cutoff for the diagnosis of CCA [94,95]. Although cutoffs vary considerably between studies, a recent meta-analysis demonstrated a diagnostic sensitivity and specificity of 0.72 and 0.84, respectively, for serum CA19-9, with an AUC of 0.83 [94].…”

“…As the most prominent example, levels of the tumour marker CA19-9 have been measured in patients with suspected CCA to define a cutoff for the diagnosis of CCA [94,95]. Although cutoffs vary considerably between studies, a recent meta-analysis demonstrated a diagnostic sensitivity and specificity of 0.72 and 0.84, respectively, for serum CA19-9, with an AUC of 0.83 [94]. In some studies, measurement of CA19-9 in serum was highly accurate for the prediction of CCA [96,97], with a sensitivity and specificity as high as of 100% and 94%, respectively using a cutoff of 186 IU/ml [97].…”