Tumor Burden Dictates Prognosis Among Patients Undergoing Resection of Intrahepatic Cholangiocarcinoma: A Tool to Guide Post-Resection Adjuvant Chemotherapy?

Introduction: While tumor burden (TB) has been associated with outcomes among patients with hepatocellular carcinoma, the role of overall TB in intrahepatic cholangiocarcinoma (ICC) remains poorly defined. Methods: Patients undergoing curative-intent resection of ICC between 2000 and 2017 were identified from a multi-institutional database. The impact of TB on overall (OS) and disease-free survival (DFS) was evaluated in the multi-institutional database and validated externally. Results: Among 1101 patients who underwent curative-intent resection of ICC, 624 (56.7%) had low TB, 346 (31.4%) medium TB, and 131 (11.9%) high TB. OS incrementally worsened with higher TB (5-year OS; low TB: 48.3% vs medium TB: 29.8% vs high TB: 17.3%, p < 0.001). Similarly, patients with low TB had better DFS compared with medium and high TB patients (5-year DFS: 38.3% vs 18.7% vs 6.9%, p < 0.001). On multivariable analysis, TB was independently associated with OS (medium TB: HR = 1.40, 95% CI 1.14–1.71; high TB: HR = 1.89, 95% CI 1.46–2.45) and DFS (medium TB, HR = 1.61, 95% CI 1.33–1.96; high TB: HR = 2.03, 95% CI 1.56–2.64). Survival analysis revealed an excellent prognostic discrimination using the TB among the external validation cohort (3-year OS; low TB: 44.8%, medium TB: 29.3%; high TB: 23.3%, p = 0.03; 3-year DFS: low TB: 32.7%, medium TB: 10.7%; high TB: 0%, p < 0.001). While neoadjuvant chemotherapy was not associated with survival across the TB groups, receipt of adjuvant chemotherapy was associated with increased survival among patients with high TB (5-year OS: 24.4% vs 13.4%, p = 0.02). Conclusion: Overall TB dictated prognosis among patients with resectable ICC. TB may be used as a tool to help guide post-resection treatment strategies.