Adjuvant chemotherapy versus chemoradiotherapy in high-risk extrahepatic cholangiocarcinoma and gallbladder carcinoma: A National Database analysis.

Abstract

e16298 Background: High-risk extrahepatic biliary tract cancers (BTC), including extrahepatic cholangiocarcinoma (EHCC) and gallbladder carcinoma (GBCA), have aggressive clinical behavior and high recurrence rates despite adjuvant chemotherapy. The benefit of adding adjuvant radiotherapy to chemotherapy following surgical resection remains uncertain. Methods: The National Cancer Database was queried for adults diagnosed between 2004 and 2023 with resected EHCC (perihilar, cystic duct, distal bile duct) or GBCA adenocarcinoma. High-risk disease was defined as pathologic T2-T4 tumors, or node positive disease, or positive surgical margins, to reflect the patient population in SWOG S0809 trial. Patients were categorized by adjuvant treatment received: chemotherapy alone or chemoradiotherapy. Baseline characteristics were compared using Wilcoxon rank-sum and Fisher’s exact tests. Overall survival (OS) was estimated using Kaplan–Meier methods and compared with the log-rank test. Multivariable Cox proportional hazards models adjusted for age and Charlson–Deyo Comorbidity Index (CDCC). Results: A total of 4724 patients were included; 1265 (27%) received adjuvant chemoradiotherapy and 3459 (73%) received chemotherapy alone. The cohort was predominantly White (78%). The chemotherapy-alone group had a higher proportion of R0 resections (71% vs 60%). On univariate analysis, patients receiving chemotherapy alone demonstrated longer median OS compared with those receiving chemoradiotherapy (36.7 vs 31.2 months; log-rank P < 0.01). In disease-specific subgroup analyses, among patients with EHCC, chemotherapy alone was associated with significantly longer median OS compared with chemoradiotherapy (38.0 vs 29.9 months; log-rank P < 0.001) (Table). On multivariable analysis, chemoradiotherapy remained associated with worse OS in the EHCC subgroup (hazard ratio 1.20; 95% confidence interval (CI), 1.06–1.37; p = 0.005). No OS difference was observed among patients with GBCA. Across both subgroups, higher pathologic T and N stages, and R1 resection were consistently associated with worse OS. Conclusions: In this national cohort of high-risk biliary tract malignancies, adjuvant chemoradiotherapy did not confer an overall survival benefit over chemotherapy alone. Chemoradiotherapy was associated with worse survival in patients with extrahepatic cholangiocarcinoma. Pathologic T and N stages, and margin status emerged as the strongest predictors of survival. BTC (GBCA+EHCC) GBCA subgroup EHCC subgroup Treatment group Median OS (months)(95% CI) Log-rank P Median OS (months)(95% CI) Log-rank P Median OS (months)(95% CI) Log-rank P Adjuvant Chemotherapy 36.67(34.43- 39.03) <0.0001 35.48(32.20- 39.23) 0.071 37.95(35.55- 41.03) <0.01 Adjuvant Chemoradiotherapy 31.18(28.19- 33.02) 32.07(28.09- 36.63) 29.90(26.28- 32.79)