Neoadjuvant Chemotherapy for Intrahepatic, Perihilar, and Distal Cholangiocarcinoma: a National Population-Based Comparative Cohort Study

Abstract Introduction Data supporting the utilization of neoadjuvant chemotherapy (NAC) in patients receiving resection for cholangiocarcinoma (CCA) remains uncertain. We aimed to determine whether NAC followed by resection improves long-term survival in intrahepatic (iCCA), perihilar (hCCA), and distal (dCCA) cholangiocarcinoma, analyzed separately. Methods Patients undergoing surgery for iCCA, hCCA, and dCCA, receiving either none, NAC, or adjuvant chemotherapy (AC) from 2010 to 2016 were identified from the National Cancer Database (NCDB). Cox regression was performed to account for selection bias and to assess the impact of surgery alone (SA) versus either NAC or AC on overall survival (OS). Results There were 9411 patients undergoing surgery for iCCA ( n = 3772, 39.5%), hCCA ( n = 1879, 20%), and dCCA ( n = 3760, 40%). Of these, 10.6% ( n = 399), 6.5% ( n = 123), and 7.2% ( n = 271) with iCCA, hCCA, and dCCA received NAC, respectively. On adjusted analyses, patients receiving NAC followed by surgery had significantly improved OS, compared to SA for iCCA ( HR 0.75, CI 95% 0.64–0.88, p < 0.001), hCCA ( HR 0.72, CI 95% 0.54–0.97, p = 0.033), and for dCCA ( HR 0.65, CI 95% 0.53–0.78, p < 0.001). However, sensitivity analyses demonstrated no differences in OS between NACs, followed by surgery or AC after surgery in iCCA ( HR 1.19, CI 95% 0.99–1.45, p = 0.068), hCCA ( HR 0.83 CI 95% 0.59–1.19, p = 0.311), and dCCA ( HR 1.13 CI 95% 0.91–1.41, p = 0.264). Conclusions This study associated NAC with increased OS for all CCA subtypes, even in patients with margin-negative and node-negative disease; however, no differences were found between NAC and AC. Our results highlight that a careful and interdisciplinary evaluation should be sought to consider NAC in CCA and warrant the need of larger studies to provide robust recommendation.