Raised CA19-9 and CEA have prognostic relevance in gallbladder carcinoma

Abstract

Background: Role of tumor markers in gall bladder carcinoma (GBC) is not well established. We evaluated the prognostic value of carbohydrate antigen 19-9 (CA19-9) and carcinoma embryonic antigen (CEA) in patients with GBC.

Methods: Of the 225 patients of GBC enrolled,176 patients were included in the study (excluded 49 patients with jaundice). Patients were divided into 3 groups; resectable n = 92, unresectable n = 17, metastatic n = 67. The clinico-pathological characteristics, tumor markers and survival data were analysed. The cutoff values of CA19-9 & CEA for predicting metastases were computed using receiver operating characteristic curve. Kaplan Meir survival and Cox regression analysis were done for factors predicting survival and recurrence.

Results: The median value of Ca19-9 was significantly higher in metastatic group [resectable: 21.3, unresectable: 53.9 and metastatic: 79; p < 0.001] but not for CEA [3.5, 7.8 and 5 ng/ml (p = 0.20)]. A cutoff value of 72 IU/ml for CA19-9, 5 ng/ml for CEA had a sensitivity and specificity of 52 and 80%, 51 and 72% respectively for detection of metastatic disease. Median, 3-year & 5-year survival were significantly lower in patients with CEA > 4 (p = 0.041), Ca19.9 > 37 (p = 0.019), T3/T4 (p = 0.001), node positive (p = 0.001) and presence of perineural invasion (p = 0.001). However, on multivariate analysis, only Ca19.9 > 37 predicted recurrence (p = 0.002, HR 5.8).

Conclusions: Raised CA19.9 and CEA predict metastatic disease in patients with GBC without jaundice with a high specificity and may help in prognostication of the patient. CA19-9 was better than CEA in prediction of tumor burden and in predicting recurrence.

Keywords: Biliary cancer; CA19–9; CEA; Gall bladder cancer; Radical cholecystectomy.

Fig. 1

a: ROC curve for CA19–9 for detection of metastasis (Area under curve: 0.674 with a cut-off value of 72 IU/ml). b: ROC curve for CEA for detection of metastasis (Area under curve: 0.628 with a cut-off value of 5 ng/ml)

Fig. 2

a: Kaplan Meir Survival graph showing significantly better survival for patients CA 19–9 ≤ 37 IU/ml as compared to CA 19–9 > 37 IU/ml. b: Kaplan Meir survival graph showing significantly better survival for patients CEA ≤4 ng/ml as compared to CEA > 4 ng/ml