The impact of peri-operative chemotherapy on the Outcomes of Patients with non-metastatic biliary tract cancer

Introduction Biliary-tract cancers, including intra- and extra-hepatic cholangiocarcinoma and gallbladder carcinoma, are uncommon but highly lethal. They represent roughly 2–3 % of new cancer diagnoses yet contribute about 5 % of cancer-related deaths. Complete surgical resection remains the foundation of curative treatment, whereas the value of peri-operative chemotherapy continues to be debated. Materials and Methods The National Cancer Database (NCDB) was queried for patients diagnosed with non- metastatic biliary tract cancer 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, chemotherapy only, adjuvant chemotherapy following surgery, and neoadjuvant chemotherapy followed by surgery) 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 biliary tract cancers were included in the analysis, of which 50.4% were females, 83% Caucasians, and 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, patients treated with surgery alone exhibited superior median OS compared with those receiving adjuvant chemotherapy (65.7 vs 50.4 months, P < 0.001). Median OS after neoadjuvant chemotherapy was numerically higher than surgery alone (79.8 vs 65.7 months); however, this difference was not statistically significant (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). The same trend was seen in stage III, patients who were treated with adjuvant and those treated with 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). Conclusion Adjuvant and neoadjuvant chemotherapy do not seem to have a survival benefit in early-stage (stage I and II) biliary tract cancers, whereas neoadjuvant chemotherapy tends to improve OS in stage III.