Anatomic patterns of recurrence in biliary tract cancers: does primary tumor site matter?

Background: Recommendations for postoperative surveillance and adjuvant therapy following curativeintent resection for biliary tract cancers-including intrahepatic and extrahepatic cholangiocarcinoma (IHCCA and EHCCA) and primary gallbladder cancer (GBC)-are uniform across primary tumor site. However, these tumors may have distinct patterns of recurrence. Methods: A retrospective observational cohort study was performed at a specialty cancer center. Patients undergoing resection of IHCCA, EHCCA, and GBC were identified (2005-2020). Recurrence-free survival (RFS) was estimated using Kaplan-Meier and Cox proportional hazard methods. Anatomic patterns of initial site of recurrence were described and compared. Results: There were 142 patients included; 50 IHCCA, 32 EHCCA, and 60 GBC. Median RFS was 30.8 months, which was not significantly different between IHCCA, EHCCA, or GBC in univariate analysis or after adjustment. Nodal positivity was significantly associated with poor RFS (HR 3.92, P <= 0.001). The most common initial site of recurrence overall was intrahepatic (n=49/64, 77%), in isolation (n=32) or synchronous with other site of recurrence (n=17). Significant differences in anatomic pattern of recurrence were observed (P=0.049) with IHCCAs more commonly recurring with simultaneous hepatic-pulmonary disease (n=5/22, 23%; EHCCA n=2/19, 10%; GBC n=1/23, 4%), GBC more commonly recurring within the porta (n=7/23, 30%; IHCCA n=0; EHCCA n=1/19, 5%), and EHCCA more commonly recurring within the peritoneum (n=5/19, 26%; IHCCA n=2/22, 9%, GBC n=2/23, 9%). Conclusions: Patterns of initial recurrence appear to differ between primary tumor site, likely reflecting underlying differences in anatomy and biology. These data could help inform future studies for adjuvant therapy as well as timing and anatomic focus for surveillance imaging.