Prognostic factors for operable biliary tract cancer: serum levels of lactate dehydrogenase, a strong association with survival

Ling Ma; Jinrong Qiu; Yaodong Zhang; Tianzhu Qiu; Biao Wang; Wensen Chen; Xiao Li; Jing Sun; Ke Wang; Xiangcheng Li; Yanhong Gu; Yongqian Shu; Xiaofeng Chen

doi:10.2147/OTT.S150502

Prognostic factors for operable biliary tract cancer: serum levels of lactate dehydrogenase, a strong association with survival

Onco Targets Ther. 2018 May 4:11:2533-2543. doi: 10.2147/OTT.S150502. eCollection 2018.

Authors

Ling Ma^#¹, Jinrong Qiu^#², Yaodong Zhang³, Tianzhu Qiu¹, Biao Wang¹, Wensen Chen⁴, Xiao Li⁵, Jing Sun¹, Ke Wang³, Xiangcheng Li³, Yanhong Gu¹, Yongqian Shu^{1

6}, Xiaofeng Chen¹

Affiliations

¹ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
² Department of Biological Therapy, Eastern Hepatobiliary Surgery Hospital Affiliated to Second Military Medical University, Shanghai, People's Republic of China.
³ Liver Transplantation Center, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
⁴ Department of Infection Management Office, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
⁵ Department of Pathology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People's Republic of China.
⁶ Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University, Nanjing, People's Republic of China.

^# Contributed equally.

Abstract

Background: Biliary tract cancers (BTCs) are uncommon but fatal, with a low 5-year survival rate after surgical resection. This study was designed to investigate the prognostic factors for operable BTC.

Methods: Baseline demographics at diagnosis were retrospectively evaluated in 341 BTC patients undergoing radical surgery at The First Affiliated Hospital of Nanjing Medical University from January 2011 to December 2015. The association between prognostic factors and overall survival (OS) was determined by multivariate analysis using the Cox proportional hazards regression model.

Results: Our study showed that 341 patients were included in the analysis, of which 166 (48.7%) were males and 175 (51.3%) were females. Older age, depth of tumor invasion, positive surgical margin, lower hemoglobin, and higher lactic dehydrogenase (LDH) were associated with significantly worse OS using multivariate analysis. In the entire cohort, the estimate of median OS in patients with LDH <271 U/L was 36.291 months (95% CI; 30.989-41.594 months), and 30.736 months (95% CI; 19.154-42.318 months) in patients with LDH ≥271 U/L (adjusted HR-1.505, 95% CI; 1.009-2.245, P = 0.045). Moreover, it was investigated whether serum LDH retained its significance as a prognostic marker in BTC subgroups separately. The results showed that LDH was prognostic in patients with distal bile duct (DBD) carcinoma undergoing radical surgery (HR-2.452, 95% CI; 1.167-5.152, P = 0.018). However, there were no statistical differences between LDH and OS in multivariate analysis in the other three individual subgroups except for DBD carcinoma. This may be due to the limited number of patients in the study, indicating that a greater number of patients may be required for statistical significance.

Conclusion: Older age, depth of tumor invasion, positive surgical margin status, lower hemoglobin levels, and elevated serum LDH level are associated with poor survival in operable BTC patients. Serum LDH level is a cost-effective prognostic biomarker in patients with operable BTC and especially DBD carcinoma.

Keywords: biliary tract cancer; lactate dehydrogenase; prognosis; radical surgery; tumor marker.