Prognostic role of tumor marker and XRCC1 polymorphism in advanced biliary tract cancer patients treated with S-1 and Cisplatin

Abstract

Background: As biliary tract cancer is a rare malignancy, prognostic and predictive markers of advanced biliary tract cancer have not been clearly elucidated. The purpose of this study is to evaluate the prognostic and predictive role of tumor marker, tumor marker change and gene polymorphism in advanced biliary tract cancer. Patients and methods: Patients with pathologically proven metastatic or relapsed biliary tract cancer who had undergone first line S-1 plus cisplatin chemotherapy were enrolled. Time to progression (TTP) and overall survival (OS) were compared. Results: Among a total of 104 patients, 69 (66.3%) patients had elevated baseline CA 19-9 level and 40 (38.5%) patients had elevated baseline CEA level. Eighty patients (77%) had either elevated CEA or CA 19-9 level. Multivariate analysis revealed that patients with elevated baseline CEA level have poorer TTP and OS compared to patients with normal CEA level. Baseline CA 19-9 level did not influence TTP or OS in multivariate analysis. Eleven germline polymorphisms within 4 genes were analyzed using polymerase chain reaction–restriction fragment length polymorphism methods. Three genes were involved in DNA damage repair and other single gene was associated with fluoropyrimidine. Only XRCC1 exon 194 gene had a negative prognostic role in terms of OS. Multivariate analysis revealed that XRCC1 194 C/T and T/T had a poor OS compared to C/C (adjusted HR 1.59, p = 0.048). In patients with elevated baseline CA 19-9, decline ≥ 30% after first cycle of chemotherapy showed prolonged TTP (5.0 vs. 8.6 months, p = 0.015) and OS (7.9 vs. 18.4 months, p < 0.001) as well as better chemotherapy response. Similar results were also obtained with CEA level change. Conclusions: Baseline CEA or XRCC1 codon 194 polymorphism had a prognostic role in advanced biliary tract cancer. CA 19-9 or CEA decline ≥ 30% after first cycle of chemotherapy serves as a positive predictive and prognostic marker.