Prognostic value of tumor marker kinetics during palliative chemotherapy in patients with unresectable gallbladder adenocarcinoma

Abstract

Background: The prognostic value of tumor markers such as CEA, CA 19-9 in gallbladder cancer are poorly understood. Previous studies used the spot measure of CEA, CA 19-9 as predictive factors but not its change during therapeutic measures. This study aimed to evaluate the relation between the change in serum CEA, CA 19-9 during palliative chemotherapy and survival in patients with unresectable gallbladder cancer. Methods: A total of 123 patients with unresectable gallbladder cancer pathologically confirmed were enrolled. Pre and post chemotherapy (2 cycles) CEA and CA 19-9 were used in analysis. The change in tumor markers were defined as the pre & post ratio of each variables. CEAchange = CEApost/CEApre, CA19-9change = CA199post/CA199pre, combined tumor marker as COMBchange = CEAchange × CA19-9change (= CEApost/CEApre*CA199post/CA199pre). Survival was compared using variable cutoffs of tumor marker change variables. Results: Patients with decreased tumor marker variables (CEA, CA19-9, CEA×CA19-9) had a better PFS and OS than those with increased tumor markers variables (PFS with 5.9 vs 2.3 months, 5.6 vs 2.2 months, 5.3 vs 2.1 months respectively, and OS with 11.4 vs 6.2 months, 9.6 vs 6.6 months, 8.9 vs 6.2 months respectively). The pre & post CA19-9 ratio had the most highest AUC value to predict 3 month progression and 1 year all-cause mortality. Patients with decreased CA19-9 value under 40% of the initial value had even better PFS (7.3 months) and OS (11.4 months) and patients with CA19-9 value increased over 200% of the initial value had an even worse PFS (2.2 months) and OS (6.5 months). Increased CA19-9 value during chemotherapy and initial CEA value over 4ng/mL were independent factors of progression with an HR of 2.34 (p<0.001) and HR of 1.67 (p=0.019) respectively, and were also independent factors of all-cause mortality with an HR of 1.57 (p=0.029) and HR of 2.21 (p<0.001) respectively Conclusion: CA 19-9 kinetics is a reliable factor predicting survival in patients with unresectable gallbladder cancer receiving palliative chemotherapy Keywords: Gallbladder cancer, CA 19-9, CEA