Neoadjuvant therapy could improve survival outcomes of locally advanced biliary tract cancer by increasing opportunities for curative resection: a systematic review and meta-analysis

Abstract

Abstract Background Neoadjuvant therapy (NAT) has been proposed as one of the promising treatment alternatives for biliary tract cancer (BTC). We report a systematic review and meta-analysis to determine the impact of NAT on survival of BTC patients. Methods We included studies evaluating neoadjuvant therapy (NAT) for BTC patients published before October 2020. Published data were extracted and computed into hazard ratios (HRs) for overall survival (OS). Subgroup analyses of benefit based on tumor subtypes and treatment modalities were specified. Data were weighted by generic inverse variance and pooled using fixed-effect or random-effect model. Results 16 studies involving 2512 patients were included in the systematic review. Single arm meta-analysis showed a pooled clinical benefit rate (CBR) of 72.86% and a curative resection rate of 37.73%. 9 studies comparing the survival of patients receiving NAT followed by curative resection (group 1) and patients receiving upfront curative resection (group 2) were included in the meta-analysis. Though patients receiving NAT were more progressive in tumor stages, there was no difference in OS between the two groups (pooled HR = 1.21; 95% CI: 0.86–1.70; P = 0.28). Intrahepatic cholangiocarcinoma (ICC) patients in the neoadjuvant group seemed to have a worse survival outcome compared to upfront curative resection group (pooled HR = 1.39; 95% CI: 1.08–1.80; P = 0.01) while extrahepatic cholangiocarcinoma (ECC) patients presented with a better survival outcome (pooled HR = 0.77; 95% CI: 0.43–1.37; P = 0.37). Those receiving NACRT (pooled HR = 0.63; 95% CI: 0.33–1.19; P = 0.16) derived greater benefit than NACT (pooled HR = 1.70; 95% CI: 1.23–2.35; P < 0.01). Conclusion For patients with non-metastatic locally advanced BTC, NAT could improve survival outcomes by increasing opportunities for curative resection to obtain a similar prognosis compared to those with initially resectable disease.