The impact of neoadjuvant therapy vs. upfront surgery on margin-negative resection rate and overall survival among intrahepatic cholangiocarcinoma patients

Abstract

Background: The microscopic negative margin (R0) surgical resection is the mainstay treatment for intrahepatic cholangiocarcinoma (ICC). Due to the rarity of ICC and the lack of level 1 evidence, there is no current consensus regarding neoadjuvant therapy versus upfront surgery approaches. Hence, we sought to assess the impact of neoadjuvant chemotherapy (NCT) ± neoadjuvant radiation (NRT) on R0, nodal status and overall survival (OS). Methods: National Cancer Data Base (NCDB)-ICC patients who underwent surgical resection were included. Uni- and multi-variate logistic regression and Cox regression models were formulated for R0, node-negative (pN0) status, and OS, respectively. Results: A total of 1765 patients with ICC were included. 446 (25%) had NCT and 143 (8%) had NRT. The upfront surgery group included 1319 patients (90% of whom had adjuvant chemotherapy). Mean age was 60 years. Median follow up was 23.5 months. The rate of pCR was 9/453 (2%). NCT group had a better rate of R0 resection (77% vs 63%, p 0.0001) and R0 patients (36 vs 23 months and 38% vs. 15%, p < 0.0001) compared to upfront surgery and non-R0 groups. Adjusting for confounding variables, multivariate cox regression models showed that young age, low tumor grade, node-negative status (pN0) (HR 0.6, 95% CI 0.46-0.67, p < 0.0001), R0 status (HR 0.7, 95% CI 0.56–0.83, p < 0.000), NCT (HR 0.8, 95% CI 0.64–0.94, p = 0.01) , NRT (0.7, 95% CI 0.47–0.96, p = 0.3) were independent predictors of lower mortality, whereas gender, race, treatment facility, Charlson-Deyo comorbidity index, tumor size and single vs. multi-agent chemotherapy were not. Conclusion: Among ICC patients, NCT showed promising rates of improved R0 resection and node-negative (pN0) stage with better OS compared to upfront surgery. Further prospective trials are warranted to confirm these findings.