The safety and efficacy of neoadjuvant chemotherapy based on our resectability criteria for locally advanced perihilar cholangiocarcinoma

Background: Neoadjuvant chemotherapy (NAC) is not commonly used for perihilar cholangiocarcinoma (PHC). This study aimed to evaluate the safety and efficacy of NAC for PHC. Patients and methods: Ninety-one PHC patients without metastases were treated at our department. They were classified as resectable (R), borderline resectable (BR), or locally advanced unresectable (LA). Upfront surgery (US) was performed for R-PHC without regional lymph node metastases (LNM). The NAC regimen consisted of two courses of gemcitabine-based chemotherapy for advanced PHC: R-PHC with LNM, BR, and LA. Results: : US and NAC were done on 32 and 59 patients, respectively. For US, 31 patients underwent resection (US-R); one with peritoneal-dissemination did not. NAC for locally advanced PHC was done in 56/59 (92%). NAC caused adverse effects in 10/59 (17%), allowed 36/59 (61%) to undergo resection (NAC-R) without impairing liver function, and spared 23/59 (39%) as un-resection (NAC-UR). Overall survival was better in the US-R and NAC-R groups than in NAC-UR (MST: 74 vs. 57 vs. 17 months, p<0.001). In 59 NAC patients, tumour size response occurred in 11/11 (100%) of R, 22/33 (66.7%) of BR, and 9/15 (60.0%) of LA patients. The un-resection rate was higher in the LA group (27% (3/11) in R, 30.3% (10/33) in BR, and 67% (10/15) in LA, p=0.039). Multivariate analyses revealed that LA and age were independent risk factors for un-resection after NAC. Conclusion: NAC is safe, and contributes to curative resection for advanced PHC. LA remained a risk factor for non-resection through NAC, and required further interventions.