Systemic Therapy Is Associated with Improved Oncologic Outcomes in Resectable Stage II/III Intrahepatic Cholangiocarcinoma: An Examination of the National Cancer Database over the Past Decade

Abstract

Limited evidence-based management guidelines for resectable intrahepatic cholangiocarcinoma (ICC) currently exist. Using a large population-based cancer registry; the utilization rates and outcomes for patients with clinical stages I-III ICC treated with neoadjuvant chemotherapy (NAT) in relation to other treatment strategies were investigated, as were the predictors of treatment regimen utilization. Oncologic outcomes were compared between treatment strategies. Amongst 2736 patients, chemotherapy utilization was low; however, NAT use increased from 4.3% to 7.2% (p = 0.011) over the study period. A higher clinical stage was predictive of the use of NAT, while higher pathologic stage and margin-positive resections were predictive of the use of adjuvant therapy (AT). For patients with more advanced disease, the receipt of NAT or AT was associated with significantly improved survival compared to surgery alone (cStage II, p = 0.040; cStage III, p = 0.003). Furthermore, patients receiving NAT were more likely to undergo margin-negative resections compared to those treated with AT (72.5% vs. 62.6%, p = 0.027), despite having higher-risk tumors. This analysis of treatment strategies for resectable ICC suggests a benefit for systemic therapy. Prospective and randomized studies evaluating the sequencing of treatments for patients with high-risk resectable ICC are needed.

Efficacy and safety comparison of neoadjuvant chemotherapy followed by surgery and upfront surgery for treating intrahepatic cholangiocarcinoma: a systematic review and meta-analysis

“…of Studies Assessment of Heterogeneity No. of patients Meta-analysis Results I 2 (%) P NC US OR ( 95% CI) P R0 resection 4 [ 32 , 44 – 46 ] 75 0.007 630 1381 0.49 (0.26–0.91) 0.02 One-year RFS 4 [ 43 – 46 ] 0 0.41 124 1256 0.95 (0.64–1.40) 0.79 Three-year RFS 4 [ 43 – 46 ] 0 0.72 124 1256 1.02 (0.68–1.52) 0.94 Five-year RFS 3 [ 44 – 46 ] 0 0.70 114 1214 0.89 (0.57–1.39) 0.60 Postoperative complications 3 [ 48 – 50 ] 67 0.05 114 1214 1.23 (0.51–2.97) 0.65 Ninety-day postoper...…”

“…Similarly, studies have shown no survival advantage when all ICC patients (stages I-III) are considered but recorded statistically significant differences in their five-year OS or median OS when only stage II-III patients were considered for analysis [ 6 , 42 ]. Additionally, Marcus et al [ 50 ] also found that for patients with more advanced disease, the receipt of neoadjuvant chemotherapy was associated with significantly improved survival compared to upfront surgery (Stage II, P = 0.040; Stage III, P = 0.003),while there was no statistically significant difference between the two treatment strategies in patients with clinical stage I ( P = 0. 30).…”

Hepatic Artery Infusion Chemotherapy for Primary and Secondary Malignancies of the Liver: State of the Art and Current High-Level Evidence

“…Patients with CCC often present with advanced disease, and survival is limited. For intrahepatic CCC (iCCC) in early stages, surgery can improve 5-year survival rates by up to 40% [ 55 ]. The role of transplantation remains controversial in unresectable disease as selection criteria are currently not well defined.…”