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Objectives: Advanced stage biliary tract cancers (BTC) are rare malignancies with poor prognosis. There are few prospective trials, but several retrospective studies regarding treatment options. In this study, we aimed to investigate the role of systemic inflammatory parameters (SIP) and other possible independent factors that may affect survival and treatment approaches and to determine the benefit of later-line treatments in these patients.Methods: A total of 284 patients, initially diagnosed with advanced stage or progressed after curative treatment of BTC, from different oncology centers in Turkey were included in this retrospective study. The prognostic significance of clinicopathological factors, SIPs and treatment options was analyzed.Results: At a median follow-up of 13 months, the median progression-free survival (PFS) was 6.1 months (95% CI:5.51-6.82), and the median overall-survival (OS) time was 16.8 months (95% CI: 13.9-19.6). Treatment choice (p < 0.001 HR:0.70 CI95% 0.55-0.9), performance status (p < 0.001 HR:2.74 CI 95% 2.12-3.54) and neutrophil-to-lymphocyte ratio (NLR) (p = 0.02 HR:1.38 CI 95% 1.03-1.84) were independent prognostic factors for PFS. For OS, the independent prognostic indicators were determined as The Eastern Cooperative Oncology Group Performance Status (ECOG PS) (p < 0.001 HR:1.78 CI 95% 1.5-2.3), Systemic Immune-inflammation Index (SII) (p < 0.001 HR:0.51 CI95% 0.36-0.73) and stage at diagnosis (p = 0.002 HR:1.79 CI 95% 1.24-2.59). Furthermore, second and third line treatments significantly prolonged OS in advanced BTC (p < 0.001 HR:0.55 CI 95% 0.38-0.79; p = 0.007 HR:0.51 CI95% 0.31-0.83, respectively).Conclusion: SII and NLR are useful prognostic factors and may be helpful in making treatment decisions. Additionally, second and later-line treatments in advanced BTC have a significant impact on survival under real-life conditions. [ABSTRACT FROM AUTHOR]