Impact of Staging Concordance and Downstaging After Neoadjuvant Therapy on Survival Following Resection of Intrahepatic Cholangiocarcinoma: A Bayesian Analysis

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Annals of Surgical Oncology


Introduction: Concordance between clinical and pathological staging, as well as the overall survival (OS) benefit associated with neoadjuvant therapy (NAT) remain ill-defined. We sought to determine the impact of staging accuracy and NAT downstaging on OS among patients with intrahepatic cholangiocarcinoma (ICC). Methods: Patients treated for ICC between 2010 and 2018 were identified using the National Cancer Database. A Bayesian approach was applied to estimate NAT downstaging. OS was assessed relative to staging concordant/overstaged disease treated with upfront surgery, understaged disease treated with upfront surgery, no downstaging, and downstaging after NAT. Results: Among 3384 patients, 2904 (85.8%) underwent upfront surgery, whereas 480 (14.2%) received NAT and 85/480 (18.4%) were downstaged. Patients with cT3 (odds ratio [OR] 2.12, 95% confidence interval [CI] 1.34–3.34), cN1 (OR 2.47, 95% CI 1.71–3.58) disease, and patients treated at high-volume facilities (OR 1.63, 95% CI 1.13–2.36) were more likely to receive NAT (all p < 0.05). Median OS was 40.1 months (95% CI 38.6–43.4). Patients with cT1-2N1 (NAT: 31.5 months vs. upfront surgery: 22.4 months; p = 0.04) and cT3-4N1 (NAT: 27.8 months vs. upfront surgery: 14.4 months; p = 0.01) disease benefited most from NAT. NAT downstaging decreased the risk of death among patients with cT3-4N1 disease (hazard ratio [HR] 0.35, 95% CI 0.15–0.82). In contrast, understaged patients with cT1-2N0/X (HR 2.15, 95% CI 1.83–2.53) and cT3-4N0/X (HR 1.71, 95% CI 1.06–2.74) disease treated with upfront surgery had increased risk of death. Conclusions: Patients with N1 ICC treated with NAT demonstrated improved OS compared with upfront surgery. Downstaging secondary to NAT conferred survival benefits among patients with cT3-4N1 versus upfront surgery. NAT should be considered in ICC patients with advanced T disease and/or nodal metastases.



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