Effect of Treatment Delay on Outcomes With Adjuvant Chemotherapy Versus Chemoradiotherapy in R1-Resected Biliary Tract Cancers

OBJECTIVES: R1 margins after biliary tract cancer (BTC) resection confer a high recurrence risk. The roles of adjuvant chemoradiotherapy and treatment timing remain incompletely defined. We compared overall survival (OS) with adjuvant chemotherapy (AC) versus adjuvant chemoradiotherapy (ACRT) and assessed whether treatment delay modifies outcomes in R1-resected BTC. METHODS: This retrospective National Cancer Database study included adults with intrahepatic cholangiocarcinoma (ICC), extrahepatic cholangiocarcinoma (ECC), or gallbladder cancer (GBC) diagnosed from 2011 to 2019 who underwent R1 resection and received adjuvant therapy. Treatment was categorized as AC or ACRT and stratified by initiation timing: timely (<60 d) versus delayed (≥60 d). Kaplan-Meier analyses, log-rank tests, and multivariable Cox regression compared OS, adjusting for age, sex, race/ethnicity, facility type, Charlson-Deyo comorbidity score, and stage. RESULTS: Of 87,340 BTC patients, 1182 (1.4%) met inclusion criteria; 616 (52.1%) initiated therapy within 60 days, and 566 (47.9%) had delayed treatment. Groups were: timely AC (29.6%), delayed AC (26.2%), timely ACRT (22.5%), and delayed ACRT (21.7%). Timely ACRT was associated with improved median OS versus timely AC (25.2 vs. 13.7 mo; HR: 0.59, 95% CI: 0.48-0.73; P<0.001). Site-specific analyses demonstrated OS benefit with ACRT in ECC and GBC, but not ICC. In GBC, delayed ACRT remained associated with improved OS. CONCLUSIONS: In R1-resected BTC, ACRT was associated with improved OS over AC alone, particularly in ECC and GBC. In GBC, delayed ACRT still conferred benefit, suggesting radiotherapy may mitigate the adverse impact of treatment delay in high-risk patients.