The impact of peri-operative chemotherapy on the outcomes of patients with non-metastatic cholangiocarcinoma.

563 Background: Cholangiocarcinoma is a rare malignancy with poor prognosis and outcome despite therapy. It accounts for 2.2% of all new cancer cases and 5% of all cancer deaths. Surgical resection is still the main therapeutic approach, whereas the role of peri-operative chemotherapy is debatable. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with non-metastatic biliary adenocarcinoma at age 18 or older between 2004 and 2019. After excluding patients with unknown timing of surgery and chemotherapy, patients who died within 90 days of the most definitive primary site surgery and patients lost to follow-up, we split the cohort into three groups according to the clinical stage (stage I-III). Then, we evaluated the overall survival (OS) between the different treatment modalities (surgery only, adjuvant chemotherapy and neoadjuvant chemotherapy) in each group. We studied the OS using Kaplan-Meier estimates and multivariate cox regression analyses to evaluate factors associated with OS. Results: A total of 35,260 patients with non-metastatic cholangiocarcinoma were included in the analysis, of which 50.4% were females, 83% Caucasians, 9.5% African Americans. The median age at diagnosis was 70 (range 18-90). 14,757 (41.9%) were stage I, 12,472 (35.4%) stage II and 8,031 (22.8%) stage III. 7,286 (20.7%) had surgical resection only, 8,144 (23.1%) had chemotherapy only, 6,964 (19.7%) had surgical resection with perioperative chemotherapy and 12,866 (36.5%) did not receive any treatment. We compared survival between different treatment modalities based on clinical stage. In stage I, we found patient who were treated with surgery only had better median OS (mOS) compared to adjuvant chemotherapy (65.7 vs 50.4 months, P<0.001) and no statistically significant difference between neoadjuvant chemotherapy and surgery only (mOS 79.8 vs 65.7 months, P=0.63). Whereas in stage II, patients who were treated with adjuvant and neoadjuvant chemotherapy had better mOS compared to those treated with surgery only (33.9 and 40.3 vs 29.9 months with P<0.001 and P=0.005, respectively). Same trend was seen in stage III, patients who were treated with adjuvant and neoadjuvant chemotherapy had better mOS compared to surgery only (22.6 and 41.5 vs 19.5 months, respectively with P<0.001 for all). In multivariate analysis, adjuvant and neoadjuvant chemotherapy did not affect the OS in all stages, except in stage III where neoadjuvant chemotherapy was associated with better OS (HR 0.646 95% CI 0.530-0.786; P<0.001). Conclusions: Adjuvant and neoadjuvant chemotherapy do not seem to have survival benefit in early stage (stage I and II) cholangiocarcinoma. Whereas neoadjuvant chemotherapy tends to improve OS in stage III.